Author: "Sola, Patrizia" / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

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1. Multiple Sclerosis Severity Score (MSSS) improves the accuracy of individualized prediction in MS

Author: Kalincik, Tomas, Kister, Ilya, Bacon, Tamar E, Malpas, Charles B, Sharmin, Sifat, Horakova, Dana, Kubala-Havrdova, Eva, Patti, Francesco, Izquierdo, Guillermo, Eichau, Sara, Ozakbas, Serkan, Onofrj, Marco, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Alroughani, Raed, Terzi, Murat, Boz, Cavit, Grand'Maison, Francois, Bergamaschi, Roberto, Gerlach, Oliver, Sa, Maria J, Kappos, Ludwig, Cartechini, Elisabetta, Lechner-Scott, Jeannette, Van Pesch, Vincent, Shaygannejad, Vahid, Granella, Franco, Spitaleri, Daniele, Iuliano, Gerardo, Maimone, Davide, Prevost, Julie, Soysal, Aysun, Turkoglu, Recai, Ampapa, Radek, Butzkueven, Helmut, Cutter, Gary, for MSBase Study Group, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
Subjects: Adult, Male, Multiple Sclerosis, Multiple Sclerosis Severity Score (MSSS), Middle Aged, Severity of Illness Index, Disability Evaluation, Neurology, prognostics, relapse prediction, Recurrence, Disease Progression, Humans, Female, Neurology (clinical), Prospective Studies
Abstract: Background: The MSBase prediction model of treatment response leverages multiple demographic and clinical characteristics to estimate hazards of relapses, confirmed disability accumulation (CDA), and confirmed disability improvement (CDI). The model did not include Multiple Sclerosis Severity Score (MSSS), a disease duration-adjusted ranked score of disability. Objective: To incorporate MSSS into the MSBase prediction model and compare model accuracy with and without MSSS. Methods: The associations between MSSS and relapse, CDA, and CDI were evaluated with marginal proportional hazards models adjusted for three principal components representative of patients’ demographic and clinical characteristics. The model fit with and without MSSS was assessed with penalized r2 and Harrell C. Results: A total of 5866 MS patients were started on disease-modifying therapy during prospective follow-up (age 38.4 ± 10.6 years; 72% female; disease duration 8.5 ± 7.7 years). Including MSSS into the model improved the accuracy of individual prediction of relapses by 31%, of CDA by 23%, and of CDI by 24% (Harrell C) and increased the amount of variance explained for relapses by 49%, for CDI by 11%, and for CDA by 10% as compared with the original model. Conclusion: Addition of a single, readily available metric, MSSS, to the comprehensive MSBase prediction model considerably improved the individual accuracy of prognostics in MS.
Published: 2022

2. Association of Latitude and Exposure to Ultraviolet B Radiation With Severity of Multiple Sclerosis: An International Registry Study

Author: Vitkova, Marianna, Diouf, Ibrahima, Malpas, Charles, Horakova, Dana, Kubala Havrdova, Eva, Patti, Francesco, Ozakbas, Serkan, Izquierdo, Guillermo, Eichau, Sara, Shaygannejad, Vahid, Onofrj, Marco, Lugaresi, Alessandra, Alroughani, Raed, Prat, Alexandre, Larochelle, Catherine, Girard, Marc, Duquette, Pierre, Terzi, Murat, Boz, Cavit, Grand'Maison, Francois, Sola, Patrizia, Ferraro, Diana, Grammond, Pierre, Butzkueven, Helmut, Buzzard, Katherine, Skibina, Olga, Yamout, Bassem I, Karabudak, Rana, Gerlach, Oliver, Lechner-Scott, Jeannette, Maimone, Davide, Bergamaschi, Roberto, Van Pesch, Vincent, Iuliano, Gerardo, Cartechini, Elisabetta, José Sà, Maria, Ampapa, Radek, Barnett, Michael, Hughes, Stella E, Ramo-Tello, Cristina M, Hodgkinson, Suzanne, Spitaleri, Daniele L A, Petersen, Thor, Butler, Ernest Gerard, Slee, Mark, McGuigan, Chris, McCombe, Pamela Ann, Granella, Franco, Cristiano, Edgardo, Prevost, Julie, Taylor, Bruce V, Sãnchez-Menoyo, Josã Luis, Laureys, Guy, Van Hijfte, Liesbeth, Vucic, Steve, Macdonell, Richard A, Gray, Orla, Olascoaga, Javier, Deri, Norma, Fragoso, Yara Dadalti, Shaw, Cameron, Kalincik, Tomas, MSBase Study Group, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
Subjects: Male, Disability Evaluation, Multiple Sclerosis, Ultraviolet Rays, Sunlight, Humans, Female, Neurology (clinical), Registries, Severity of Illness Index, Research Article
Abstract: Background and ObjectivesThe severity of multiple sclerosis (MS) varies widely among individuals. Understanding the determinants of this heterogeneity will help clinicians optimize the management of MS. The aim of this study was to investigate the association between latitude of residence, UV B radiation (UVB) exposure, and the severity of MS.MethodsThis observational study used the MSBase registry data. The included patients met the 2005 or 2010 McDonald diagnostic criteria for MS and had a minimum dataset recorded in the registry (date of birth, sex, clinic location, date of MS symptom onset, disease phenotype at baseline and censoring, and ≥1 Expanded Disability Status Scale score recorded). The latitude of each study center and cumulative annualized UVB dose at study center (calculated from National Aeronautics and Space Administration’s Total Ozone Mapping Spectrometer) at ages 6 and 18 years and the year of disability assessment were calculated. Disease severity was quantified with Multiple Sclerosis Severity Score (MSSS). Quadratic regression was used to model the associations between latitude, UVB, and MSSS.ResultsThe 46,128 patients who contributed 453,208 visits and a cumulative follow-up of 351,196 patient-years (70% women, mean age 39.2 ± 12 years, resident between latitudes 19°35′ and 56°16′) were included in this study. Latitude showed a nonlinear association with MS severity. In latitudes DiscussionIn temperate zones, MS severity is associated with latitude. This association is mainly, but not exclusively, driven by UVB exposure contributing to both MS susceptibility and severity.
Published: 2022

3. Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years

Author: Kalincik, Tomas, Diouf, Ibrahima, Sharmin, Sifat, Malpas, Charles, Spelman, Tim, Horakova, Dana, Havrdova, Eva Kubala, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Jokubaitis, Vilija, van der Walt, Anneke, Grand'Maison, Francois, Sola, Patrizia, Ferraro, Diana, Shaygannejad, Vahid, Alroughani, Raed, Hupperts, Raymond, Terzi, Murat, Boz, Cavit, Lechner-Scott, Jeannette, Pucci, Eugenio, Van Pesch, Vincent, Granella, Franco, Bergamaschi, Roberto, Spitaleri, Daniele, Slee, Mark, Vucic, Steve, Ampapa, Radek, McCombe, Pamela, Ramo-Tello, Cristina, Prevost, Julie, Olascoaga, Javier, Cristiano, Edgardo, Barnett, Michael, Saladino, Maria Laura, Sanchez-Menoyo, Jose Luis, Hodgkinson, Suzanne, Rozsa, Csilla, Hughes, Stella, Moore, Fraser, Shaw, Cameron, Butler, Ernest, Skibina, Olga, Gray, Orla, Kermode, Allan, Csepany, Tunde, Singhal, Bhim, Shuey, Neil, Piroska, Imre, Taylor, Bruce, Simo, Magdolna, Sirbu, Carmen-Adella, Sas, Attila, Butzkueven, Helmut, MSBase Study Group, UCL - (SLuc) Service de neurologie, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Kalincik, Toma, Diouf, Ibrahima, Sharmin, Sifat, Malpas, Charle, Spelman, Tim, Horakova, Dana, Havrdova, Eva Kubala, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Jokubaitis, Vilija, van der Walt, Anneke, Grand'Maison, Francoi, Sola, Patrizia, Ferraro, Diana, Shaygannejad, Vahid, Alroughani, Raed, Hupperts, Raymond, Terzi, Murat, Boz, Cavit, Lechner-Scott, Jeannette, Pucci, Eugenio, Van Pesch, Vincent, Granella, Franco, Bergamaschi, Roberto, Spitaleri, Daniele, Slee, Mark, Vucic, Steve, Ampapa, Radek, McCombe, Pamela, Ramo-Tello, Cristina, Prevost, Julie, Olascoaga, Javier, Cristiano, Edgardo, Barnett, Michael, Saladino, Maria Laura, Sanchez-Menoyo, Jose Lui, Hodgkinson, Suzanne, Rozsa, Csilla, Hughes, Stella, Moore, Fraser, Shaw, Cameron, Butler, Ernest, Skibina, Olga, Gray, Orla, Kermode, Allan, Csepany, Tunde, Singhal, Bhim, Shuey, Neil, Piroska, Imre, Taylor, Bruce, Simo, Magdolna, Sirbu, Carmen-Adella, Sas, Attila, and Butzkueven, Helmut
Subjects: Adult, Male, medicine.medical_specialty, Article, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, multiple sclerosis, treatment, prognosis, Internal medicine, medicine, Humans, Immunologic Factors, Disease Progression, Female, Fingolimod Hydrochloride, Glatiramer Acetate, Immunosuppressive Agents, Interferon-beta, Longitudinal Studies, Middle Aged, Proportional Hazards Models, 030212 general & internal medicine, Glatiramer acetate, Expanded Disability Status Scale, Proportional hazards model, business.industry, Multiple sclerosis, Hazard ratio, medicine.disease, Confidence interval, Cohort, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: ObjectiveTo test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients.MethodsWe studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity.ResultsA total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval [CI] 0.43–0.82, p = 0.0016), worsening of disability (0.56, 0.38–0.82, p = 0.0026), and progress to EDSS step 6 (0.33, 0.19–0.59, p = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50–0.70, p = 10−9) and worsening of disability (0.81, 0.67–0.99, p = 0.043).ConclusionContinued treatment with MS immunotherapies reduces disability accrual by 19%–44% (95% CI 1%–62%), the risk of need of a walking aid by 67% (95% CI 41%–81%), and the frequency of relapses by 40–41% (95% CI 18%–57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term.Classification of EvidenceThis study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability.
Published: 2021

4. Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis

Author: Wilkins, Alastair, Slee, Mark, TERZİ, MURAT, Grand'Maison, Francois, Ferraro, Diana, Sola, Patrizia, Van Pesch, Vincent, McCombe, Pamela, Hupperts, Raymond, Alroughani, Raed, Grammond, Pierre, Bergamaschi, Roberto, Lugaresi, Alessandra, Shaygannejad, Vahid, Pucci, Eugenio, Granella, Franco, Jokubaitis, Vilija, Pearson, Owen R., Ziemssen, Tjalf, Hutchinson, Michael, McGuigan, Christopher, Butzkueven, Helmut, Kalincik, Tomas, Onofrj, Marco, Trojano, Maria, Duquette, Pierre, Girard, Marc, Prat, Alexandre, Izquierdo, Guillermo, Havrdova, Eva, Horakova, Dana, Zwanikken, Cees, Soysal, Aysun, Yamout, Bassem, Piroska, Imre, McDonnell, Gavin, Moore, Fraser, Butler, Ernest, De Luca, Giovanna, Di Tommaso, Valeria, Travaglini, Daniela, Pietrolongo, Erika, di Ioia, Maria, Farina, Deborah, Mancinelli, Luca, Hodgkinson, Suzanne, Oreja-Guevara, Celia, BOZ, CAVİT, Prevost, Julie, Olascoaga, Javier, Van Wijmeersch, Bart, Barnett, Michael, Verheul, Freek, Rojas, Juan Ingacio, Spitaleri, Daniele, Rio, Maria Edite, Taylor, Bruce, Luis Sanchez-Menoyo, Jose, Ramo-Tello, Cristina, Solaro, Claudio, Csepany, Tunde, Iuliano, Gerardo, Skibina, Olga, Petersen, Thor, Bolanos, Ricardo Fernandez, Sidhom, Youssef, Riadh, Riadh, Vucic, Steve, Macdonell, Richard, Sempere, Angel Perez, Simo, Magdolna, Kister, Ilya, Shuey, Neil, Radek, Radek, Dominguez, Jose Andres, Pia Amato, Maria, Saladino, Maria Laura, Kermode, Allan, Brown, J. William L., Coles, Alasdair, Lechner-Scott, Jeannette, Willis, Mark, Rice, Claire, Scolding, Neil, Flechter, Schlomo, Harding, Katharine, Jones, Joanne, Robertson, Neil, Hughes, Stella, ÖZAKBAŞ, SERKAN, Brown, J William L, Coles, Alasdair, Horakova, Dana, Havrdova, Eva, Izquierdo, Guillermo, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Trojano, Maria, Lugaresi, Alessandra, Bergamaschi, Roberto, Grammond, Pierre, Alroughani, Raed, Hupperts, Raymond, McCombe, Pamela, Van Pesch, Vincent, Sola, Patrizia, Ferraro, Diana, Grand'Maison, Francoi, Terzi, Murat, Lechner-Scott, Jeannette, Flechter, Schlomo, Slee, Mark, Shaygannejad, Vahid, Pucci, Eugenio, Granella, Franco, Jokubaitis, Vilija, Willis, Mark, Rice, Claire, Scolding, Neil, Wilkins, Alastair, Pearson, Owen R, Ziemssen, Tjalf, Hutchinson, Michael, Harding, Katharine, Jones, Joanne, McGuigan, Christopher, Butzkueven, Helmut, Kalincik, Toma, Robertson, Neil, Brown, Will [0000-0002-7737-5834], Coles, Alasdair [0000-0003-4738-0760], Jones, Joanna [0000-0003-4974-1371], Apollo - University of Cambridge Repository, DIPARTIMENTO DI SCIENZE BIOMEDICHE E NEUROMOTORIE, UCL - SSS/IONS - Institute of NeuroScience, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, and OMÜ
Subjects: Male, INTERFERON-BETA, MULTICENTER, Interferon-beta/therapeutic use, multiple sclerosis, 01 natural sciences, Cohort Studies, 0302 clinical medicine, Natalizumab, 030212 general & internal medicine, Alemtuzumab, Original Investigation, GLATIRAMER ACETATE, NATALIZUMAB, Natalizumab/therapeutic use, OUTCOMES, treatment, ALEMTUZUMAB, Absolute risk reduction, General Medicine, Immunologic Factors/therapeutic use, Fingolimod, TIME, Disease Progression, Female, Immunosuppressive Agents, medicine.drug, Cohort study, Adult, medicine.medical_specialty, Alemtuzumab/therapeutic use, Lower risk, Time-to-Treatment, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, medicine, Humans, Immunologic Factors, 0101 mathematics, Glatiramer acetate, Fingolimod Hydrochloride/therapeutic use, business.industry, Fingolimod Hydrochloride, Multiple sclerosis, DISABILITY, 010102 general mathematics, Glatiramer Acetate, Interferon-beta, Multiple Sclerosis, Relapsing-Remitting/drug therapy, medicine.disease, FINGOLIMOD, Immunosuppressive Agents/therapeutic use, multiple sclerosis, progression, treatment, progression, business, Glatiramer Acetate/therapeutic use
Abstract: none 40 si his study was financially supported by National Health and Medical Research Council of Australia (fellowships 1140766 and 1080518, project grants 1129189 and 1083539), the University of Melbourne (Faculty of Medicine, Dentistry and Health Sciences research fellowship), a Next Generation Fellowship funded by the Grand Charity of the Freemason’s (recipient JWLB), and the MSBase 2017 Fellowship (recipient JWLB). Alemtuzumab studies done in Cambridge were supported by the NIHR Cambridge Biomedical Research Centre and the MS Society UK. The MSBase Foundation is a not-for-profit organization that receives support from Roche, Merck, Biogen, Novartis, Bayer Schering, Sanofi Genzyme, and Teva. IMPORTANCE: Within 2 decades of onset, 80% of untreated patients with relapsing-remitting multiple sclerosis (MS) convert to a phase of irreversible disability accrual termed secondary progressive MS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition. OBJECTIVE: To determine the association between the use, the type of, and the timing of DMTs with the risk of conversion to secondary progressive MS diagnosed with a validated definition. DESIGN, SETTING, AND PARTICIPANTS: Cohort study with prospective data from 68 neurology centers in 21 countries examining patients with relapsing-remitting MS commencing DMTs (or clinical monitoring) between 1988-2012 with minimum 4 years' follow-up. EXPOSURES: The use, type, and timing of the following DMTs: interferon beta, glatiramer acetate, fingolimod, natalizumab, or alemtuzumab. After propensity-score matching, 1555 patients were included (last follow-up, February 14, 2017). MAIN OUTCOME AND MEASURE: Conversion to objectively defined secondary progressive MS. RESULTS: Of the 1555 patients, 1123 were female (mean baseline age, 35 years [SD, 10]). Patients initially treated with glatiramer acetate or interferon beta had a lower hazard of conversion to secondary progressive MS than matched untreated patients (HR, 0.71; 95% CI, 0.61-0.81; P
Published: 2019

5. Long-term outcomes in patients presenting with optic neuritis: Analyses of the MSBase registry

Author: Kenney, Rachel, Liu, Mengling, Patil, Sachi, Alroughani, Raed, Ampapa, Radek, Bergamaschi, Roberto, Boz, Cavit, Butzkueven, Helmut, Gomez, Jose Cabrera, Cartechini, Elisabetta, Madueño, Sara Eichau, Ferraro, Diana, Grand-Maison, Francois, Granella, Franco, Horakova, Dana, Izquierdo Ayuso, Guillermo, Kalincik, Tomas, Lizrova Preiningerova, Jana, Lugaresi, Alessandra, Onofrj, Marco, Ozakbas, Serkan, Patti, Francesco, Sola, Patrizia, Soysal, Aysun, Spitaleri, Daniele Litterio A, Terzi, Murat, Turkoglu, Recai, Van Pesch, Vincent, Saidha, Shiv, Thorpe, Lorna E, Galetta, Steven L, Balcer, Laura J, Kister, Ilya, Spelman, Tim, MSBase Study Group, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Kenney R., Liu M., Patil S., Alroughani R., Ampapa R., Bergamaschi R., Boz C., Butzkueven H., Gomez J.C., Cartechini E., Madueno S.E., Ferraro D., Grand-Maison F., Granella F., Horakova D., Izquierdo Ayuso G., Kalincik T., Lizrova Preiningerova J., Lugaresi A., Onofrj M., Ozakbas S., Patti F., Sola P., Soysal A., Spitaleri D.L.A., Terzi M., Turkoglu R., van Pesch V., Saidha S., Thorpe L.E., Galetta S.L., Balcer L.J., Kister I., and Spelman T.
Subjects: Registrie, Adult, Optic neuriti, medicine.medical_specialty, Multiple Sclerosis, Optic Neuritis, Adolescent, Expanded disability status scale (EDSS), Vision, Cohort Studies, Disability Evaluation, Young Adult, Internal medicine, Multiple Sclerosi, medicine, Humans, Optic neuritis, Registries, Young adult, Survival analysis, Clinically isolated syndrome, Expanded Disability Status Scale, business.industry, Demyelinating Disease, medicine.disease, Clinical research, MSBase registry, Neurology, Cohort, Disease Progression, Female, Neurology (clinical), Cohort Studie, business, Human, Demyelinating Diseases, Cohort study
Abstract: Background: Short-term outcomes of optic neuritis (ON) have been well characterized. Limited data exists on longer-term visual outcomes in patients who present with ON. The large MSBase registry allows for characterization of long-term visual outcomes after ON. Methods: Via the MSBase Registry, data on patients from 41 centers was collected during routine clinical and research visits. Physical and visual disability were measured using the expanded disability status scale (EDSS) and the visual function score (VFS). Inclusion criteria for this analysis included age ≥ 18 years, clinically isolated syndrome (CIS), ON-onset, baseline visit within 6 months of onset, and at least one follow-up visit. Survival analysis was used to evaluate the association of disease-modifying treatment with time to conversion to clinically definite MS or sustained EDSS/VFS progression. Results: Data from 60,933 patients were obtained from the MSBase registry in July 2019. Of these, 1317 patients met inclusion criteria; 935 were treated at some point in disease course, while 382 were never treated. At baseline, mean age was 32.3 ± 8.8 years, 74% were female, median EDSS was 2 (IQR 1–2), and median VFS was 1 (IQR 0–2). Median follow-up time was 5.2 years (IQR 2.4–9.3). Treatment was associated with reduced risk and delayed conversion to clinically definite MS (HR = 0.70, p < 0.001), sustained EDSS progression (HR = 0.46, p < 0.0001) and sustained VFS (HR = 0.41, p < 0.001) progression. Conclusions: In the MSBase cohort, treatment after ON was associated with better visual and neurological outcomes compared to no treatment. These results support early treatment for patients presenting with ON as the first manifestation of MS.
Published: 2021

6. Prognostic indicators in pediatric clinically isolated syndrome

Author: Iaffaldano, Pietro, Simone, Marta, Lucisano, Giuseppe, Ghezzi, Angelo, Coniglio, Gabriella, Brescia Morra, Vincenzo, Salemi, Giuseppe, Patti, Francesco, Lugaresi, Alessandra, Izquierdo, Guillermo, Bergamaschi, Roberto, Cabrera-Gomez, Jose Antonio, Pozzilli, Carlo, Millefiorini, Enrico, Alroughani, Raed, Boz, Cavit, Pucci, Eugenio, Zimatore, Giovanni Bosco, Sola, Patrizia, Lus, Giacomo, Maimone, Davide, Avolio, Carlo, Cocco, Eleonora, Sajedi, Seyed Aidin, Costantino, Gianfranco, Duquette, Pierre, Shaygannejad, Vahid, Petersen, Thor, Fernández Bolaños, Ricardo, Paolicelli, Damiano, Tortorella, Carla, Spelman, Tim, Margari, Lucia, Amato, Maria Pia, Comi, Giancarlo, Butzkueven, Helmut, Trojano, Maria, Spitaleri, Daniele, Rottoli, Maria Rosa, Ardito, Bonaventura, Iuliano, Gerardo, Montanari, Enrico, Granieri, Enrico, Tedeschi, Gioacchino, Bertolotto, Antonio, Granella, Franco, Di Battista, Giancarlo, Gallo, Paolo, Cavalla, Paola, Bellantonio, Paolo, De Robertis, Francesca, Durelli, Luca, Scarpini, Elio, Rezzonico, Monica, Protti, Alessandra, Solaro, Claudio, Corea, Francesco, Bosco, Antonio, Vianello, Marika, Ferrò, Maria Teresa, Balgera, Roberto, Grasso, Roberta, De Luca, Giovanna, Farina, Deboah, Travaglini, Daniela, di Ioia, Maria, Di Tommaso, Valeria, Mancinelli, Luca, Pietrolongo, Erika, Hupperts, Raymond, Rio, Maria Edite, Terzi, Murat, Barnett, Michael, Slee, Mark, Van Pesch, Vincent, Savino, Aldo, Lechner-Scott, Jeannette, Grammond, Pierre, Singhal, Bhim, Zwanikken, Cees, Fiol, Marcela, Patrucco, Liliana, Paine, Mark, Mccombefrom, Pamela, Grand'Maison, Francois, Iaffaldano, Pietro, Simone, Marta, Lucisano, Giuseppe, Ghezzi, Angelo, Coniglio, Gabriella, Brescia Morra, Vincenzo, Salemi, Giuseppe, Patti, Francesco, Lugaresi, Alessandra, Izquierdo, Guillermo, Bergamaschi, Roberto, Cabrera-Gomez, Jose Antonio, Pozzilli, Carlo, Millefiorini, Enrico, Alroughani, Raed, Boz, Cavit, Pucci, Eugenio, Zimatore, Giovanni Bosco, Sola, Patrizia, Lus, Giacomo, Maimone, Davide, Avolio, Carlo, Cocco, Eleonora, Sajedi, Seyed Aidin, Costantino, Gianfranco, Duquette, Pierre, Shaygannejad, Vahid, Petersen, Thor, Fernández Bolaños, Ricardo, Paolicelli, Damiano, Tortorella, Carla, Spelman, Tim, Margari, Lucia, Amato, Maria Pia, Comi, Giancarlo, Butzkueven, Helmut, Trojano, Maria, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Neurologie (9), Klinische Neurowetenschappen, Morra, Vincenzo Brescia, Cabrera Gomez, Jose Antonio, and Bolaños, Ricardo Fernández
Subjects: Registrie, Male, Multiple Sclerosis, Adolescent, Age of Onset, Child, Demyelinating Diseases, Female, Follow-Up Studies, Humans, Prognosis, Retrospective Studies, Risk Factors, Disease Progression, Registries, Neurology, Neurology (clinical), Prognosi, ONSET MULTIPLE-SCLEROSIS, CHILDHOOD, CHILDREN, PARACLINICAL FEATURES, DISABILITY PROGRESSION, NO, Follow-Up Studie, Retrospective Studie, prognostic indicators, Multiple Sclerosi, pediatric, multiple sclerosis, prognosis, indicators, OPTIC NEURITIS, Risk Factor, Demyelinating Disease, NATURAL-HISTORY, multiple sclerosis, clinically isolated syndrome, prognostic indicators, TRANSVERSE MYELITIS, clinically isolated syndrome, INTERFERON BETA-1B, Settore MED/26 - Neurologia, FOLLOW-UP, Human
Abstract: To assess prognostic factors for a second clinical attack and a first disability worsening event in pediatric clinically isolated syndrome (pCIS) suggestive of Multiple Sclerosis (MS) patients. Objective: To assess prognostic factors for a second clinical attack and a first disability-worsening event in pediatric clinically isolated syndrome (pCIS) suggestive of multiple sclerosis (MS) patients. Methods: A cohort of 770 pCIS patients was followed up for at least 10 years. Cox proportional hazard models and Recursive Partitioning and Amalgamation (RECPAM) tree-regression were used to analyze data. Results: In pCIS, female sex and a multifocal onset were risk factors for a second clinical attack (hazard ratio [HR], 95% confidence interval [CI] = 1.28, 1.06â1.55; 1.42, 1.10â1.84, respectively), whereas disease-modifying drug (DMD) exposure reduced this risk (HR, 95% CI = 0.75, 0.60â0.95). After pediatric onset MS (POMS) diagnosis, age at onset younger than 15 years and DMD exposure decreased the risk of a first Expanded Disability Status Scale (EDSS)-worsening event (HR, 95% CI = 0.59, 0.42â0.83; 0.75, 0.71â0.80, respectively), whereas the occurrence of relapse increased this risk (HR, 95% CI = 5.08, 3.46â7.46). An exploratory RECPAM analysis highlighted a significantly higher incidence of a first EDSS-worsening event in patients with multifocal or isolated spinal cord or optic neuritis involvement at onset in comparison to those with an isolated supratentorial or brainstem syndrome. A Cox regression model including RECPAM classes confirmed DMD exposure as the most protective factor against EDSS-worsening events and relapses as the most important risk factor for attaining EDSS worsening. Interpretation: This work represents a step forward in identifying predictors of unfavorable course in pCIS and POMS and supports a protective effect of early DMD treatment in preventing MS development and disability accumulation in this population. Ann Neurol 2017;81:729â739.
Published: 2017

7. Exome Sequencing Reveals VCP Mutations as a Cause of Familial ALS

Author: Johnson, Janel O., Mandrioli, Jessica, Benatar, Michael, Abramzon, Yevgeniya, Van Deerlin, Vivianna M., Trojanowski, John Q., Gibbs, J. Raphael, Brunetti, Maura, Gronka, Susan, Wuu, Joanne, Ding, Jinhui, Mccluskey, Leo, Martinez Lage, Maria, Falcone, Dana, Hernandez, Dena G., Arepalli, Sampath, Chong, Sean, Schymick, Jennifer C., Rothstein, Jeffrey, Landi, Francesco, Wang, Yong Dong, Calvo, Andrea, Mora, Gabriele, Sabatelli, Mario, Battistini, Stefania, Salvi, Fabrizio, Spataro, Rossella, Sola, Patrizia, Borghero, Giuseppe, Giannini, Fabio, Ricci, Claudia, Moglia, Cristina, Ossola, Irene, Canosa, Antonio, Gallo, Sara, Bartolomei, Ilaria, Marinou, Kalliopi, Papetti, Laura, Conte, Amelia, Luigetti, Marco, La Bella, Vincenzo, Paladino, Piera, Caponnetto, Claudia, Volanti, Paolo, Marrosu, Maria Teresa, Murru, Maria Rita, Galassi, Giuliana, Scholz, Sonja W., Taylor, J. Paul, Restagno, Gabriella, Chiò, Adriano, Traynor, Bryan J., MONSURRO', Maria Rosaria, TEDESCHI, Gioacchino, Johnson, JO, Mandrioli, J, Benatar, M, Abramzon, Y, Van Deerlin, VM, Trojanowski, JQ, Gibbs, JR, Brunetti, M, Gronka, S, Wuu, J, Ding, J, McCluskey, L, Martinez-Lage, M, Falcone, D, Hernandez, DG, Arepalli, S, Chong, S, Schymick, JC, Rothstein, J, Landi, F, Wang, Y-D, Calvo, A, Mora, G, Sabatelli, M, Monsurrò, MR, Battistini, S, Salvi, F, Spataro, R, Sola, P, Borghero, G, Galassi, G, Scholz, SW, Taylor, JP, Restagno, G, Chiò, A, Traynor, BJ, Johnson, Janel O., Mandrioli, Jessica, Benatar, Michael, Abramzon, Yevgeniya, Van Deerlin, Vivianna M., Trojanowski, John Q., Gibbs, J. Raphael, Brunetti, Maura, Gronka, Susan, Wuu, Joanne, Ding, Jinhui, Mccluskey, Leo, Martinez Lage, Maria, Falcone, Dana, Hernandez, Dena G., Arepalli, Sampath, Chong, Sean, Schymick, Jennifer C., Rothstein, Jeffrey, Landi, Francesco, Wang, Yong Dong, Calvo, Andrea, Mora, Gabriele, Sabatelli, Mario, Monsurro', Maria Rosaria, Battistini, Stefania, Salvi, Fabrizio, Spataro, Rossella, Sola, Patrizia, Borghero, Giuseppe, Giannini, Fabio, Ricci, Claudia, Moglia, Cristina, Ossola, Irene, Canosa, Antonio, Gallo, Sara, Tedeschi, Gioacchino, Bartolomei, Ilaria, Marinou, Kalliopi, Papetti, Laura, Conte, Amelia, Luigetti, Marco, La Bella, Vincenzo, Paladino, Piera, Caponnetto, Claudia, Volanti, Paolo, Marrosu, Maria Teresa, Murru, Maria Rita, Galassi, Giuliana, Scholz, Sonja W., Taylor, J. Paul, Restagno, Gabriella, Chiò, Adriano, and Traynor, Bryan J.
Subjects: Adenosine Triphosphatase, Male, Cell Cycle Proteins, UBQLN2, Cohort Studies, 0302 clinical medicine, Reference Values, Valosin Containing Protein, Cell Cycle Protein, Reference Value, Amyotrophic lateral sclerosis, Exome sequencing, Adenosine Triphosphatases, Genetics, 0303 health sciences, General Neuroscience, Exons, Middle Aged, Pedigree, 3. Good health, Multisystem proteinopathy, Female, Settore MED/26 - Neurologia, Case-Control Studie, Chromosomes, Human, Pair 9, Human, Frontotemporal dementia, Neuroscience(all), Valosin-containing protein, Exon, Biology, Protein degradation, TARDBP, Article, 03 medical and health sciences, medicine, Humans, Aged, 030304 developmental biology, Amyotrophic lateral sclerosis, familial ALS, exome sequencing, Neuroscience (all), business.industry, Amyotrophic Lateral Sclerosis, medicine.disease, Amino Acid Substitution, Case-Control Studies, Mutation, biology.protein, Cohort Studie, business, 030217 neurology & neurosurgery, Amyotrophic Lateral Sclerosi
Abstract: Summary Using exome sequencing, we identified a p.R191Q amino acid change in the valosin-containing protein ( VCP ) gene in an Italian family with autosomal dominantly inherited amyotrophic lateral sclerosis (ALS). Mutations in VCP have previously been identified in families with Inclusion Body Myopathy, Paget disease, and Frontotemporal Dementia (IBMPFD). Screening of VCP in a cohort of 210 familial ALS cases and 78 autopsy-proven ALS cases identified four additional mutations including a p.R155H mutation in a pathologically proven case of ALS. VCP protein is essential for maturation of ubiquitin-containing autophagosomes, and mutant VCP toxicity is partially mediated through its effect on TDP-43 protein, a major constituent of ubiquitin inclusions that neuropathologically characterize ALS. Our data broaden the phenotype of IBMPFD to include motor neuron degeneration, suggest that VCP mutations may account for ∼1%–2% of familial ALS, and provide evidence directly implicating defects in the ubiquitination/protein degradation pathway in motor neuron degeneration.
Published: 2010

8. Fingolimod versus interferon beta/glatiramer acetate after natalizumab suspension in multiple sclerosis

Author: Iaffaldano, Pietro, Lucisano, Giuseppe, Pozzilli, Carlo, Brescia Morra, Vincenzo, Ghezzi, Angelo, Millefiorini, Enrico, Patti, Francesco, Zimatore, Giovanni Bosco, Marrosu, Maria Giovanna, Amato, Maria Pia, Bertolotto, Antonio, Bergamaschi, Roberto, Granella, Franco, Coniglio, Gabriella, Tedeschi, Gioacchino, Sola, Patrizia, Lus, Giacomo, Ferrò, Maria Teresa, Iuliano, Gerardo, Corea, Francesco, Protti, Alessandra, Cavalla, Paola, Guareschi, Angelica, Rodegher, Mariaemma, Paolicelli, Damiano, Tortorella, Carla, Lepore, Vito, Prosperini, Luca, Saccà, Francesco, Baroncini, Damiano, Comi, Giancarlo, Trojano, Maria, Italian iMed Web database, LUGARESI, ALESSANDRA, Iaffaldano, Pietro, Lucisano, Giuseppe, Pozzilli, Carlo, Brescia Morra, Vincenzo, Ghezzi, Angelo, Millefiorini, Enrico, Patti, Francesco, Lugaresi, Alessandra, Zimatore, Giovanni Bosco, Marrosu, Maria Giovanna, Amato, Maria Pia, Bertolotto, Antonio, Bergamaschi, Roberto, Granella, Franco, Coniglio, Gabriella, Tedeschi, Gioacchino, Sola, Patrizia, Lus, Giacomo, Ferrò, Maria Teresa, Iuliano, Gerardo, Corea, Francesco, Protti, Alessandra, Cavalla, Paola, Guareschi, Angelica, Rodegher, Mariaemma, Paolicelli, Damiano, Tortorella, Carla, Lepore, Vito, Prosperini, Luca, Saccà, Francesco, Baroncini, Damiano, Comi, Giancarlo, Trojano, Maria, Italian iMed-Web database, Iaffaldano, P, Lucisano, G, Pozzilli, C, Brescia Morra, V, Ghezzi, A, Millefiorini, E, Patti, F, Lugaresi, A, Zimatore, Gb, Marrosu, Mg, Amato, Mp, Bertolotto, A, Bergamaschi, R, Granella, F, Coniglio, G, Tedeschi, G, Sola, P, Lus, G, Ferrò, Mt, Iuliano, G, Corea, F, Protti, A, Cavalla, P, Guareschi, A, Rodegher, M, Paolicelli, D, Tortorella, C, Lepore, V, Prosperini, L, Saccà, F, Baroncini, D, Trojano, M, Italian iMed Web, Database, BRESCIA MORRA, Vincenzo, Sacca', Francesco, and DIPARTIMENTO DI SCIENZE BIOMEDICHE E NEUROMOTORIE
Subjects: Registrie, Male, fingolimod, glatiramer acetate, interferon beta, multiple sclerosis, natalizumab discontinuation, Adult, Cohort Studies, Drug Substitution, Drug Therapy, Combination, Female, Fingolimod Hydrochloride, Glatiramer Acetate, Humans, Immunologic Factors, Immunosuppressive Agents, Interferon-beta, Italy, Middle Aged, Multiple Sclerosis, Relapsing-Remitting, Natalizumab, Poisson Distribution, Prospective Studies, Regression Analysis, Treatment Outcome, Registries, Medicine (all), Arts and Humanities (miscellaneous), Neurology (clinical), Relapsing-Remitting, Rate ratio, Gastroenterology, Immunosuppressive Agent, Immunologic Factor, Medicine, Prospective cohort study, Hazard ratio, Fingolimod, multiple sclerosi, Combination, medicine.drug, Human, medicine.medical_specialty, Multiple Sclerosis, Regression Analysi, Drug Therapy, Internal medicine, Glatiramer acetate, business.industry, Multiple sclerosis, medicine.disease, fingolimod, multiple sclerosis, Surgery, Prospective Studie, Cohort Studie, business
Abstract: none 34 no studio multicentrico The comparative effectiveness of fingolimod versus interferon beta/glatiramer acetate was assessed in a multicentre, observational, prospectively acquired cohort study including 613 patients with relapsing multiple sclerosis discontinuing natalizumab in the Italian iMedWeb registry. First, after natalizumab suspension, the relapse risk during the untreated wash-out period and during the course of switch therapies was estimated through Poisson regression analyses in separated models. During the wash-out period an increased risk of relapses was found in patients with a higher number of relapses before natalizumab treatment (incidence rate ratio = 1.31, P = 0.0014) and in patients discontinuing natalizumab due to lack of efficacy (incidence rate ratio = 2.33, P = 0.0288), patient's choice (incidence rate ratio = 2.18, P = 0.0064) and adverse events (incidence rate ratio = 2.09, P = 0.0084). The strongest independent factors influencing the relapse risk after the start of switch therapies were a wash-out duration longer than 3 months (incidence rate ratio = 1.78, P < 0.0001), the number of relapses experienced during and before natalizumab treatment (incidence rate ratio = 1.61, P < 0.0001; incidence rate ratio = 1.13, P = 0.0118, respectively) and the presence of comorbidities (incidence rate ratio = 1.4, P = 0.0097). Switching to fingolimod was associated with a 64% reduction of the adjusted-risk for relapse in comparison with switching to interferon beta/glatiramer acetate (incidence rate ratio = 0.36, P < 0.0001). Secondly, patients who switched to fingolimod or to interferon beta/glatiramer acetate were propensity score-matched on a 1-to-1 basis at the switching date. In the propensity score-matched sample a Poisson model showed a significant lower incidence of relapses in patients treated with fingolimod in comparison with those treated with interferon beta/glatiramer acetate (incidence rate ratio = 0.52, P = 0.0003) during a 12-month follow-up. The cumulative probability of a first relapse after the treatment switch was significantly lower in patients receiving fingolimod than in those receiving interferon beta/glatiramer acetate (P = 0.028). The robustness of this result was also confirmed by sensitivity analyses in subgroups with different wash-out durations (less or more than 3 months). Time to 3-month confirmed disability progression was not significantly different between the two groups (Hazard ratio = 0.58; P = 0.1931). Our results indicate a superiority of fingolimod in comparison to interferon beta/glatiramer acetate in controlling disease reactivation after natalizumab discontinuation in the real life setting. none Iaffaldano, Pietro; Lucisano, Giuseppe; Pozzilli, Carlo; Brescia Morra, Vincenzo; Ghezzi, Angelo; Millefiorini, Enrico; Patti, Francesco; Lugaresi, Alessandra; Zimatore, Giovanni Bosco; Marrosu, Maria Giovanna; Amato, Maria Pia; Bertolotto, Antonio; Bergamaschi, Roberto; Granella, Franco; Coniglio, Gabriella; Tedeschi, Gioacchino; Sola, Patrizia; Lus, Giacomo; Ferrò, Maria Teresa; Iuliano, Gerardo; Corea, Francesco; Protti, Alessandra; Cavalla, Paola; Guareschi, Angelica; Rodegher, Mariaemma; Paolicelli, Damiano; Tortorella, Carla; Lepore, Vito; Prosperini, Luca; Saccà, Francesco; Baroncini, Damiano; Comi, Giancarlo; Trojano, Maria; Italian iMed-Web database Iaffaldano, Pietro; Lucisano, Giuseppe; Pozzilli, Carlo; Brescia Morra, Vincenzo; Ghezzi, Angelo; Millefiorini, Enrico; Patti, Francesco; Lugaresi, Alessandra; Zimatore, Giovanni Bosco; Marrosu, Maria Giovanna; Amato, Maria Pia; Bertolotto, Antonio; Bergamaschi, Roberto; Granella, Franco; Coniglio, Gabriella; Tedeschi, Gioacchino; Sola, Patrizia; Lus, Giacomo; Ferrò, Maria Teresa; Iuliano, Gerardo; Corea, Francesco; Protti, Alessandra; Cavalla, Paola; Guareschi, Angelica; Rodegher, Mariaemma; Paolicelli, Damiano; Tortorella, Carla; Lepore, Vito; Prosperini, Luca; Saccà, Francesco; Baroncini, Damiano; Comi, Giancarlo; Trojano, Maria; Italian iMed-Web database
Published: 2015

9. Predictors of long-term disability accrual in relapse-onset multiple sclerosis

Author: Jokubaitis, Vilija G, Spelman, Tim, Kalincik, Tomas, Lorscheider, Johannes, Havrdova, Eva, Horakova, Dana, Duquette, Pierre, Girard, Marc, Prat, Alexandre, Izquierdo, Guillermo, Grammond, Pierre, Van Pesch, Vincent, Pucci, Eugenio, Grand'Maison, François, Hupperts, Raymond, Granella, Franco, Sola, Patrizia, Bergamaschi, Roberto, Iuliano, Gerardo, Spitaleri, Daniele, Boz, Cavit, Hodgkinson, Suzanne, Olascoaga, Javier, Verheul, Freek, McCombe, Pamela, Petersen, Thor, Rozsa, Csilla, Lechner-Scott, Jeannette, Saladino, Maria Laura, Farina, Deborah, Iaffaldano, Pietro, Paolicelli, Damiano, Butzkueven, Helmut, Lugaresi, Alessandra, Trojano, Maria, and MSBase Study Group
Subjects: Adult, Male, Multiple Sclerosis, Glatiramer Acetate, Interferon-beta, Protective Factors, Prognosis, Disability Evaluation, Young Adult, Pregnancy, Recurrence, Risk Factors, Humans, Female, Registries, Follow-Up Studies
Abstract: To identify predictors of 10-year Expanded Disability Status Scale (EDSS) change after treatment initiation in patients with relapse-onset multiple sclerosis. Using data obtained from MSBase, we defined baseline as the date of first injectable therapy initiation. Patients need only have remained on injectable therapy for 1 day and were monitored on any approved disease-modifying therapy, or no therapy thereafter. Median EDSS score changes over a 10-year period were determined. Predictors of EDSS change were then assessed using median quantile regression analysis. Sensitivity analyses were further performed. We identified 2,466 patients followed up for at least 10 years reporting post-baseline disability scores. Patients were treated an average 83% of their follow-up time. EDSS scores increased by a median 1 point (interquartile range = 0-2) at 10 years post-baseline. Annualized relapse rate was highly predictive of increases in median EDSS over 10 years (coeff = 1.14, p = 1.9 × 10(-22) ). On-therapy relapses carried greater burden than off-therapy relapses. Cumulative treatment exposure was independently associated with lower EDSS at 10 years (coeff = -0.86, p = 1.3 × 10(-9) ). Furthermore, pregnancies were also independently associated with lower EDSS scores over the 10-year observation period (coeff = -0.36, p = 0.009). We provide evidence of long-term treatment benefit in a large registry cohort, and provide evidence of long-term protective effects of pregnancy against disability accrual. We demonstrate that high annualized relapse rate, particularly on-treatment relapse, is an indicator of poor prognosis. Ann Neurol 2016;80:89-100.
Published: 2016

10. Predictors of long-term disability accrual in relapse-onset multiple sclerosis

Author: Jokubaitis, Vilija G., Spelman, Tim, Kalincik, Tomas, Lorscheider, Johannes, Havrdova, Eva, Horakova, Dana, Duquette, Pierre, Girard, Marc, Prat, Alexandre, Izquierdo, Guillermo, Grammond, Pierre, Van Pesch, Vincent, Pucci, Eugenio, Grand'Maison, Francois, Hupperts, Raymond, Granella, Franco, Sola, Patrizia, Bergamaschi, Roberto, Iuliano, Gerardo, Spitaleri, Daniele, Boz, Cavit, Hodgkinson, Suzanne, Olascoaga, Javier, Verheul, Freek, McCombe, Pamela, Petersen, Thor, Rozsa, Csilla, Lechner-Scott, Jeannette, Laura Saladino, Maria, Farina, Deborah, Iaffaldano, Pietro, Paolicelli, Damiano, Butzkueven, Helmut, Lugaresi, Alessandra, Trojano, Maria, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, MUMC+: MA Med Staf Spec Neurologie (9), and Klinische Neurowetenschappen
Subjects: Adult, Male, Multiple Sclerosis, Glatiramer Acetate, Interferon-beta, Protective Factors, Prognosis, Disability Evaluation, Young Adult, Pregnancy, Recurrence, Risk Factors, Journal Article, Humans, Female, Registries, Follow-Up Studies
Abstract: OBJECTIVE: To identify predictors of 10-year Expanded Disability Status Scale (EDSS) change after treatment initiation in patients with relapse-onset multiple sclerosis.METHODS: Using data obtained from MSBase, we defined baseline as the date of first injectable therapy initiation. Patients need only have remained on injectable therapy for 1 day and were monitored on any approved disease-modifying therapy, or no therapy thereafter. Median EDSS score changes over a 10-year period were determined. Predictors of EDSS change were then assessed using median quantile regression analysis. Sensitivity analyses were further performed.RESULTS: We identified 2,466 patients followed up for at least 10 years reporting post-baseline disability scores. Patients were treated an average 83% of their follow-up time. EDSS scores increased by a median 1 point (interquartile range = 0-2) at 10 years post-baseline. Annualized relapse rate was highly predictive of increases in median EDSS over 10 years (coeff = 1.14, p = 1.9 × 10(-22) ). On-therapy relapses carried greater burden than off-therapy relapses. Cumulative treatment exposure was independently associated with lower EDSS at 10 years (coeff = -0.86, p = 1.3 × 10(-9) ). Furthermore, pregnancies were also independently associated with lower EDSS scores over the 10-year observation period (coeff = -0.36, p = 0.009).INTERPRETATION: We provide evidence of long-term treatment benefit in a large registry cohort, and provide evidence of long-term protective effects of pregnancy against disability accrual. We demonstrate that high annualized relapse rate, particularly on-treatment relapse, is an indicator of poor prognosis. Ann Neurol 2016;80:89-100.
Published: 2015

11. Treatment of relapsing-remitting multiple sclerosis after 24 doses of natalizumab: evidence from an Italian spontaneous, prospective, and observational study (the TY-STOP Study)

Author: Clerico, Marinella, Schiavetti, Irene, De Mercanti, Stefania F, Piazza, Federico, Gned, Dario, Brescia Morra, Vincenzo, Lanzillo, Roberta, Ghezzi, Angelo, Bianchi, Anna, Salemi, Giuseppe, Realmuto, Sabrina, Sola, Patrizia, Vitetta, Francesca, Cavalla, Paola, Paolicelli, Damiano, Trojano, Maria, Sormani, Maria Pia, Durelli, Luca, Ferraro, Diana, Clerico, M, Schiavetti, I, De Mercanti, SF, Piazza, F, Gned, D, Brescia Morra, V, Lanzillo, R, Ghezzi, A, Bianchi, A, Salemi, G, Realmuto, S, Sola, P, Vitetta, F, Cavalla, P, Paolicelli, D, Trojano, M, Sormani, MP, and Durelli L
Subjects: Adult, Male, medicine.medical_specialty, Antibodies, Monoclonal, Humanized, Humans, Italy, Magnetic Resonance Imaging, Middle Aged, Multiple Sclerosis, Relapsing-Remitting, Natalizumab, Prospective Studies, Recurrence, Treatment Outcome, Internal medicine, Clinical endpoint, medicine, Outpatient clinic, Glatiramer acetate, Multiple Sclerosis, Ty-STOP, Natalizumab, business.industry, Progressive multifocal leukoencephalopathy, medicine.disease, Fingolimod, Surgery, Discontinuation, Clinical trial, Settore MED/26 - Neurologia, Neurology (clinical), business, medicine.drug
Abstract: Importance The evaluation of therapeutic choices is needed after 24 doses of natalizumab in patients with multiple sclerosis (MS). Objective To evaluate the effect of therapeutic choices on the mean annualized relapse rate and on magnetic resonance imaging MS activity after 24 doses of natalizumab in patients with relapsing-remitting MS. Design, Setting, and Participants The TY-STOP study, which recruited participants between October 22, 2010, and October 22, 2012, at 8 Italian MS centers (secondary care outpatient clinics) among 124 adult patients who demonstrated no clinical or magnetic resonance imaging MS activity after 24 doses of natalizumab. Interventions Natalizumab, no treatment, interferon beta, glatiramer acetate, or fingolimod. Main Outcomes and Measures The primary end point was the mean annualized relapse rate. Statistical analyses were performed in 124 patients with complete follow-up data among 130 patients who were recruited and stratified into study groups. In the intent-to-treat group, the decision was made to continue or interrupt natalizumab after 24 doses. In the as-treated group, natalizumab continuers received natalizumab, natalizumab switchers changed to different therapies, and natalizumab quitters discontinued natalizumab during the study year. Results No significant differences in demographic or baseline clinical characteristics were found among the study participants. In the intent-to-treat group (n = 124), clinical (P = .004) and radiologic (P = .02) MS activity was significantly lower in patients continuing natalizumab (n = 43) than in patients interrupting natalizumab (n = 81), with a protective effect of natalizumab continuation on both outcomes (odds ratio [OR], 0.33; 95% CI, 0.15-0.70 for clinical activity and OR, 0.35; 95% CI, 0.15-0.79 for radiologic activity). In the as-treated group (n = 124), clinical (P = .003) and radiologic (P = .03) MS activity was significantly lower in natalizumab continuers than in natalizumab switchers or quitters, confirming a protective effect of natalizumab on the risk of relapse in natalizumab continuers compared with natalizumab quitters (OR, 4.40; 95% CI, 1.72-11.23) and natalizumab switchers (OR, 3.28; 95% CI, 0.99-10.79). No disease rebound was observed in natalizumab quitters. After natalizumab discontinuation, 1 patient developed progressive multifocal leukoencephalopathy during the observation period, with complete recovery. Conclusions and Relevance This study provides class III evidence of an increased risk of MS activity resumption after natalizumab discontinuation. Therapy discontinuation after 24 doses in natalizumab-responding patients should be considered only if the risk of progressive multifocal leukoencephalopathy is high and outweighs the benefits of continuing the drug. Trial Registration Osservatorio Nazionale Sulla Sperimentazione Clinica dei Medicinali No. 131/2010.
Published: 2014

12. Delay from treatment start to full effect of immunotherapies for multiple sclerosis

Author: Roos, Izanne, Leray, Emmanuelle, Frascoli, Federico, Casey, Romain, Brown, J William L, Horakova, Dana, Havrdova, Eva, Trojano, Maria, Patti, Francesco, Izquierdo, Guillermo, Eichau, Sara, Onofrj, Marco, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Ozakbas, Serkan, Bergamaschi, Roberto, Sá, Maria José, Cartechini, Elisabetta, Boz, Cavit, Granella, Franco, Hupperts, Raymond, Terzi, Murat, Lechner-Scott, Jeannette, Spitaleri, Daniele, Van Pesch, Vincent, Soysal, Aysun, Olascoaga, Javier, Prevost, Julie, Aguera-Morales, Eduardo, Slee, Mark, Csepany, Tunde, Turkoglu, Recai, Sidhom, Youssef, Gouider, Riadh, Van Wijmeersch, Bart, McCombe, Pamela, Macdonell, Richard, Coles, Alasdair, Malpas, Charles, Butzkueven, Helmut, Vukusic, Sandra, Kalincik, Tomas, Duquette, Pierre, Grand'Maison, Francois, Iuliano, Gerardo, Ramo-Tello, Cristina, Solaro, Claudio, Cabrera-Gomez, Jose Antonio, Rio, Maria Edite, Bolaños, Ricardo Fernandez, Shaygannejad, Vahid, Oreja-Guevara, Celia, Sanchez-Menoyo, Jose Luis, Petersen, Thor, Altintas, Ayse, Barnett, Michael, Flechter, Shlomo, Fragoso, Yara, Amato, Maria Pia, Moore, Fraser, Ampapa, Radek, Verheul, Freek, Hodgkinson, Suzanne, Cristiano, Edgardo, Yamout, Bassem, Laureys, Guy, Dominguez, Jose Andres, Zwanikken, Cees, Deri, Norma, Dobos, Eniko, Vrech, Carlos, Butler, Ernest, Rozsa, Csilla, Petkovska-Boskova, Tatjana, Karabudak, Rana, Rajda, Cecilia, Alkhaboori, Jabir, Saladino, Maria Laura, Shaw, Cameron, Shuey, Neil, Vucic, Steve, Sempere, Angel Perez, Campbell, Jamie, Piroska, Imre, Taylor, Bruce, van der Walt, Anneke, Kappos, Ludwig, Roullet, Etienne, Gray, Orla, Simo, Magdolna, Sirbu, Carmen-Adella, Brochet, Bruno, Cotton, François, De Sèze, Jérôme, Dion, Armelle, Douek, Pascal, Guillemin, Francis, Laplaud, David, Lebrun-Frenay, Christine, Moreau, Thibault, Olaiz, Javier, Pelletier, Jean, Rigaud-Bully, Claire, Stankoff, Bruno, Marignier, Romain, Debouverie, Marc, Edan, Gilles, Ciron, Jonathan, Ruet, Aurélie, Collongues, Nicolas, Lubetzki, Catherine, Vermersch, Patrick, Labauge, Pierre, Defer, Gilles, Cohen, Mikaël, Fromont, Agnès, Wiertlewsky, Sandrine, Berger, Eric, Clavelou, Pierre, Audoin, Bertrand, Giannesini, Claire, Gout, Olivier, Thouvenot, Eric, Heinzlef, Olivier, Al-Khedr, Abdullatif, Bourre, Bertrand, Casez, Olivier, Cabre, Philippe, Montcuquet, Alexis, Créange, Alain, Camdessanché, Jean-Philippe, Faure, Justine, Maurousset, Aude, Patry, Ivania, Hankiewicz, Karolina, Pottier, Corinne, Maubeuge, Nicolas, Labeyrie, Céline, Nifle, Chantal, University of Melbourne, The Royal Melbourne Hospital, Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), Swinburne University of Technology [Melbourne], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, University of Cambridge [UK] (CAM), Medicine Charles University and General Faculty Hospital in Prague, University of Bari Aldo Moro (UNIBA), University of Catania [Italy], Hospital Universitario Virgen Macarena [Seville, Spain], University 'G. d'Annunzio' of Chieti-Pescara [Chieti], Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Université de Montréal (UdeM), University of Modena and Reggio Emilia, Partenaires INRAE, Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ), IRCCS Mondino Foundation, Universidade Fernando Pessoa, KTU Medical Faculty Farabi Hospital, University of Parma = Università degli studi di Parma [Parme, Italie], Zuyderland Ziekenhuis, Medical Faculty [Samsun, Turkey], University of Newcastle [Australia] (UoN), Université Catholique de Louvain = Catholic University of Louvain (UCL), Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Hospital Universitario Donostia, Hospital Universitario Reina Sofía de Córdoba, Instituto Maimonides de Investigación Biomédica de Córdoba (IMIBIC), Haydarpasa Numune Training and Research Hospital, Hasselt University (UHasselt), University of Queensland [Brisbane], Hitachi Cambridge Laboratory [University of Cambridge], Hitachi, Ltd-University of Cambridge [UK] (CAM), Monash University [Melbourne], Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Ospedali Riuniti di Salerno, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), 1157717, National Health and Medical Research Council, Biogen, MSIF-ARSEP McDonald, Melbourne Research Scholarship, French State, ‘Agence Nationale de la Recherche,’, ANR-10-COHO-002, ‘Investments for the Future’, Eugène Devic EDMUS Foundation, ARSEP Foundation, Novartis, Merck, Roche, Teva Pharmaceutical Industries, Sanofi Genzyme, EDMUS Foundation, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Roos I., Leray E., Frascoli F., Casey R., Brown W.J.L., Horakova D., Havrdova E.K., Trojano M., Patti F., Izquierdo G., Eichau S., Onofrj M., Lugaresi A., Prat A., Girard M., Grammond P., Sola P., Ferraro D., Ozakbas S., Bergamaschi R., Sa M.J., Cartechini E., Boz C., Granella F., Hupperts R., Terzi M., Lechner-Scott J., Spitaleri D., van Pesch V., Soysal A., Olascoaga J., Prevost J., Aguera-Morales E., Slee M., Csepany T., Turkoglu R., Sidhom Y., Gouider R., van Wijmeersch B., McCombe P., Macdonell R., Coles A., Malpas C.B., Butzkueven H., Vukusic S., Kalincik T., Duquette P., Grand'Maison F., Iuliano G., Ramo-Tello C., Solaro C., Cabrera-Gomez J.A., Rio M.E., Bolanos R.F., Shaygannejad V., Oreja-Guevara C., Sanchez-Menoyo J.L., Petersen T., Altintas A., Barnett M., Flechter S., Fragoso Y., Amato M.P., Moore F., Ampapa R., Verheul F., Hodgkinson S., Cristiano E., Yamout B., Laureys G., Dominguez J.A., Zwanikken C., Deri N., Dobos E., Vrech C., Butler E., Rozsa C., Petkovska-Boskova T., Karabudak R., Rajda C., Alkhaboori J., Saladino M.L., Shaw C., Shuey N., Vucic S., Sempere A.P., Campbell J., Piroska I., Taylor B., van der Walt A., Kappos L., Roullet E., Gray O., Simo M., Sirbu C.-A., Brochet B., Cotton F., de Seze J., Dion A., Douek P., Guillemin F., Laplaud D., Lebrun-Frenay C., Moreau T., Olaiz J., Pelletier J., Rigaud-Bully C., Stankoff B., Marignier R., Debouverie M., Edan G., Ciron J., Ruet A., Collongues N., Lubetzki C., Vermersch P., Labauge P., Defer G., Cohen M., Fromont A., Wiertlewsky S., Berger E., Clavelou P., Audoin B., Giannesini C., Gout O., Thouvenot E., Heinzlef O., Al-Khedr A., Bourre B., Casez O., Cabre P., Montcuquet A., Creange A., Camdessanche J.-P., Faure J., Maurousset A., Patry I., Hankiewicz K., Pottier C., Maubeuge N., Labeyrie C., Nifle C., Brown, Will [0000-0002-7737-5834], Coles, Alasdair [0000-0003-4738-0760], Apollo - University of Cambridge Repository, McCombe, Pamela/0000-0003-2704-8517, Slee, Mark/0000-0003-4323-2453, Brown, William/0000-0002-7737-5834, Laplaud, David/0000-0001-6113-6938, Ciron, Jonathan/0000-0002-3386-6308, Roos, Izanne/0000-0003-0371-3666, Lugaresi, Alessandra/0000-0003-2902-5589, Aguera-Morales, Eduardo/0000-0002-8604-2054, Kalincik, Tomas, Girard, Marc, Patti, Francesco, Horakova, Dana, Malpas, Charles B., Olascoaga, Javier, Prevost, Julie, Roos, Izanne, Hupperts, Raymond, Csepany, Tunde, VAN WIJMEERSCH, Bart, Ferraro, Diana, Aguera-Morales, Eduardo, Cartechini, Elisabetta, Vukusic, Sandra, Frascoli, Federico, Lugaresi, Alessandra, Sa, Maria Jose, Butzkueven, Helmut, Spitaleri, Daniele, Macdonell, Richard, Coles, Alasdair, Havrdova, Eva K., Granella, Franco, Turkoglu, Recai, Trojano, Maria, Sola, Patrizia, Van Pesch, Vincent, Onofrj, Marco, Grammond, Pierre, Bergamaschi, Roberto, Izquierdo, Guillermo, McCombe, Pamela, Slee, Mark, Eichau, Sara, Prat, Alexandre, Leray, Emmanuelle, Soysal, Aysun, Terzi, Murat, Brown, J. William L., Boz, Cavit, Sidhom, Youssef, Gouider, Riadh, Ozakbas, Serkan, Casey, Romain, Lechner-Scott, Jeannette, Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Hospital Universitario Virgen Macarena [Séville], Università degli studi di Parma = University of Parma (UNIPR), University of Newcastle [Callaghan, Australia] (UoN), University of Cambridge [UK] (CAM)-Hitachi, Ltd, and ANR-10-COHO-0002,OFSEP,Observatoire Français de la Sclérose en Plaques(2010)
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Time Factors, multiple sclerosis, law.invention, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Randomized controlled trial, law, Internal medicine, medicine, Humans, Immunologic Factors, Multiple sclerosi, 030212 general & internal medicine, Prospective Studies, Registries, Prospective cohort study, therapeutic lag, business.industry, Multiple sclerosis, Interferon beta-1a, Middle Aged, medicine.disease, Fingolimod, 3. Good health, Treatment Outcome, Cohort, Disease Progression, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, Neurology (clinical), business, Immunotherapies, 030217 neurology & neurosurgery, Immunosuppressive Agents, Therapeutic lag, prognosis, treatment, medicine.drug, Cohort study, Follow-Up Studies
Abstract: In multiple sclerosis, treatment start or switch is prompted by evidence of disease activity. Whilst immunomodulatory therapies reduce disease activity, the time required to attain maximal effect is unclear. In this study we aimed to develop a method that allows identification of the time to manifest fully and clinically the effect of multiple sclerosis treatments ('therapeutic lag') on clinical disease activity represented by relapses and progression-of-disability events. Data from two multiple sclerosis registries, MSBase (multinational) and OFSEP (French), were used. Patients diagnosed with multiple sclerosis, minimum 1-year exposure to treatment, minimum 3-year pretreatment follow-up and yearly review were included in the analysis. For analysis of disability progression, all events in the subsequent 5-year period were included. Density curves, representing incidence of relapses and 6-month confirmed progression events, were separately constructed for each sufficiently represented therapy. Monte Carlo simulations were performed to identify the first local minimum of the first derivative after treatment start; this point represented the point of stabilization of treatment effect, after the maximum treatment effect was observed. The method was developed in a discovery cohort (MSBase), and externally validated in a separate, non-overlapping cohort (OFSEP). A merged MSBase-OFSEP cohort was used for all subsequent analyses. Annualized relapse rates were compared in the time before treatment start and after the stabilization of treatment effect following commencement of each therapy. We identified 11 180 eligible treatment epochs for analysis of relapses and 4088 treatment epochs for disability progression. External validation was performed in four therapies, with no significant difference in the bootstrapped mean differences in therapeutic lag duration between registries. The duration of therapeutic lag for relapses was calculated for 10 therapies and ranged between 12 and 30 weeks. The duration of therapeutic lag for disability progression was calculated for seven therapies and ranged between 30 and 70 weeks. Significant differences in the pre- versus post-treatment annualized relapse rate were present for all therapies apart from intramuscular interferon beta-1a. In conclusion we have developed, and externally validated, a method to objectively quantify the duration of therapeutic lag on relapses and disability progression in different therapies in patients more than 3 years from multiple sclerosis onset. Objectively defined periods of expected therapeutic lag allows insights into the evaluation of treatment response in randomized clinical trials and may guide clinical decision-making in patients who experience early on-treatment disease activity. This method will subsequently be applied in studies that evaluate the effect of patient and disease characteristics on therapeutic lag. This study was supported by the EDMUS Foundation, Biogen and NHMRC (1140766, 1129189, 1157717). I.R. is supported by a MSIF-ARSEP McDonald fellowship grant and a Melbourne Research Scholarship. The MSBase Foundation is a not-for-profit organization that receives support from Biogen, Novartis, Merck, Roche, Teva and Sanofi Genzyme. The Observatoire Francais de la Sclerose en Plaques (OFSEP) is supported by a grant provided by the French State and handled by the 'Agence Nationale de la Recherche,' within the framework of the 'Investments for the Future' program, under the reference ANR-10-COHO-002, by the Eugene Devic EDMUS Foundation against multiple sclerosis and by the ARSEP Foundation. The study was conducted separately and apart from the guidance of the sponsors. Kalincik, T (corresponding author), Univ Melbourne, Dept Med, CORe, 300 Grattan St, Melbourne, Vic 3050, Australia. tomas.kalincik@unimelb.edu.au

13. Delay from treatment start to full effect of immunotherapies for multiple sclerosis

Author: Roos, Izanne, Leray, Emmanuelle, Frascoli, Federico, Casey, Romain, Brown, J William L, Horakova, Dana, Havrdova, Eva K, Trojano, Maria, Patti, Francesco, Izquierdo, Guillermo, Eichau, Sara, Onofrj, Marco, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Ozakbas, Serkan, Bergamaschi, Roberto, Sá, Maria José, Cartechini, Elisabetta, Boz, Cavit, Granella, Franco, Hupperts, Raymond, Terzi, Murat, Lechner-Scott, Jeannette, Spitaleri, Daniele, Van Pesch, Vincent, Soysal, Aysun, Olascoaga, Javier, Prevost, Julie, Aguera-Morales, Eduardo, Slee, Mark, Csepany, Tunde, Turkoglu, Recai, Sidhom, Youssef, Gouider, Riadh, Van Wijmeersch, Bart, McCombe, Pamela, Macdonell, Richard, Coles, Alasdair, Malpas, Charles B, Butzkueven, Helmut, Vukusic, Sandra, Kalincik, Tomas, MSBase, and OFSEP Investigators
Subjects: Adult, Male, Multiple Sclerosis, Time Factors, Natalizumab, Middle Aged, 3. Good health, therapeutic lag, Cohort Studies, Treatment Outcome, Disease Progression, Humans, Immunologic Factors, Female, Prospective Studies, Registries, Immunosuppressive Agents, Follow-Up Studies
Abstract: In multiple sclerosis, treatment start or switch is prompted by evidence of disease activity. Whilst immunomodulatory therapies reduce disease activity, the time required to attain maximal effect is unclear. In this study we aimed to develop a method that allows identification of the time to manifest fully and clinically the effect of multiple sclerosis treatments ('therapeutic lag') on clinical disease activity represented by relapses and progression-of-disability events. Data from two multiple sclerosis registries, MSBase (multinational) and OFSEP (French), were used. Patients diagnosed with multiple sclerosis, minimum 1-year exposure to treatment, minimum 3-year pretreatment follow-up and yearly review were included in the analysis. For analysis of disability progression, all events in the subsequent 5-year period were included. Density curves, representing incidence of relapses and 6-month confirmed progression events, were separately constructed for each sufficiently represented therapy. Monte Carlo simulations were performed to identify the first local minimum of the first derivative after treatment start; this point represented the point of stabilization of treatment effect, after the maximum treatment effect was observed. The method was developed in a discovery cohort (MSBase), and externally validated in a separate, non-overlapping cohort (OFSEP). A merged MSBase-OFSEP cohort was used for all subsequent analyses. Annualized relapse rates were compared in the time before treatment start and after the stabilization of treatment effect following commencement of each therapy. We identified 11 180 eligible treatment epochs for analysis of relapses and 4088 treatment epochs for disability progression. External validation was performed in four therapies, with no significant difference in the bootstrapped mean differences in therapeutic lag duration between registries. The duration of therapeutic lag for relapses was calculated for 10 therapies and ranged between 12 and 30 weeks. The duration of therapeutic lag for disability progression was calculated for seven therapies and ranged between 30 and 70 weeks. Significant differences in the pre- versus post-treatment annualized relapse rate were present for all therapies apart from intramuscular interferon beta-1a. In conclusion we have developed, and externally validated, a method to objectively quantify the duration of therapeutic lag on relapses and disability progression in different therapies in patients more than 3 years from multiple sclerosis onset. Objectively defined periods of expected therapeutic lag allows insights into the evaluation of treatment response in randomized clinical trials and may guide clinical decision-making in patients who experience early on-treatment disease activity. This method will subsequently be applied in studies that evaluate the effect of patient and disease characteristics on therapeutic lag.

14. Towards personalized therapy for multiple sclerosis: prediction of individual treatment response

Author: Suzanne Hodgkinson, Patrizia Sola, Jose Luis Sanchez-Menoyo, Mark Slee, Vahid Shaygannejad, Alexandre Prat, Jeannette Lechner-Scott, Lukas Sobisek, Raymond Hupperts, Vincent Van Pesch, Cristina Ramo-Tello, Csilla Rozsa, Guillermo Izquierdo, Helmut Butzkueven, Fraser Moore, Pamela A. McCombe, Maria Laura Saladino, Murat Terzi, Vilija Jokubaitis, Cavit Boz, Eugenio Pucci, Raed Alroughani, Shlomo Flechter, Pierre Grammond, Roberto Bergamaschi, G. Iuliano, Daniele Spitaleri, Francois Grand'Maison, Ali Manouchehrinia, Pierre Duquette, Tomas Kalincik, Marc Girard, Radek Ampapa, Michael Barnett, Jan Hillert, Freek Verheul, Maria Trojano, Franco Granella, Edgardo Cristiano, Maria Pia Amato, Dana Horakova, Alessandra Lugaresi, Celia Oreja-Guevara, Steve Vucic, Eva Havrdova, Tim Spelman, Javier Olascoaga, Kalincik, Toma, Manouchehrinia, Ali, Sobisek, Luka, Jokubaitis, Vilija, Spelman, Tim, Horakova, Dana, Havrdova, Eva, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Girard, Marc, Prat, Alexandre, Duquette, Pierre, Grammond, Pierre, Sola, Patrizia, Hupperts, Raymond, Grand'Maison, Francoi, Pucci, Eugenio, Boz, Cavit, Alroughani, Raed, Van Pesch, Vincent, Lechner-scott, Jeannette, Terzi, Murat, Bergamaschi, Roberto, Iuliano, Gerardo, Granella, Franco, Spitaleri, Daniele, Shaygannejad, Vahid, Oreja-guevara, Celia, Slee, Mark, Ampapa, Radek, Verheul, Freek, Mccombe, Pamela, Olascoaga, Javier, Amato, Maria Pia, Vucic, Steve, Hodgkinson, Suzanne, Ramo-tello, Cristina, Flechter, Shlomo, Cristiano, Edgardo, Rozsa, Csilla, Moore, Fraser, Sanchez-menoyo, Jose Lui, Saladino, Maria Laura, Barnett, Michael, Hillert, Jan, Butzkueven, Helmut, DIPARTIMENTO DI SCIENZE BIOMEDICHE E NEUROMOTORIE, OMÜ, [Kalincik, Tomas] Univ Melbourne, CORE, Dept Med, 300 Grattan St, Melbourne, Vic 3050, Australia, [Kalincik, Tomas] Royal Melbourne Hosp, Dept Neurol, 300 Grattan St, Melbourne, Vic 3050, Australia, [Jokubaitis, Vilija] Royal Melbourne Hosp, Dept Neurol, 300 Grattan St, Melbourne, Vic 3050, Australia, [Spelman, Tim] Royal Melbourne Hosp, Dept Neurol, 300 Grattan St, Melbourne, Vic 3050, Australia, [Manouchehrinia, Ali] Karolinska Inst, Dept Clin Neurosci, SE-17177 Stockholm, Sweden, [Sobisek, Lukas] Gen Univ Hosp, Dept Neurol, Katerinska 30, Prague 12808, Czech Republic, [Horakova, Dana] Gen Univ Hosp, Dept Neurol, Katerinska 30, Prague 12808, Czech Republic, [Havrdova, Eva] Gen Univ Hosp, Dept Neurol, Katerinska 30, Prague 12808, Czech Republic, [Sobisek, Lukas] Gen Univ Hosp, Ctr Clin Neurosci, Katerinska 30, Prague 12808, Czech Republic, [Horakova, Dana] Gen Univ Hosp, Ctr Clin Neurosci, Katerinska 30, Prague 12808, Czech Republic, [Havrdova, Eva] Gen Univ Hosp, Ctr Clin Neurosci, Katerinska 30, Prague 12808, Czech Republic, [Sobisek, Lukas] Charles Univ Prague, Katerinska 30, Prague 12808, Czech Republic, [Horakova, Dana] Charles Univ Prague, Katerinska 30, Prague 12808, Czech Republic, [Havrdova, Eva] Charles Univ Prague, Katerinska 30, Prague 12808, Czech Republic, [Sobisek, Lukas] Univ Econ Prague, Dept Stat & Probabil, Winston Churchill Sq 1938-4, Prague 13067, Czech Republic, [Jokubaitis, Vilija] Univ Melbourne, Dept Med, 300 Grattan St, Melbourne, Vic 3050, Australia, [Spelman, Tim] Univ Melbourne, Dept Med, 300 Grattan St, Melbourne, Vic 3050, Australia, [Trojano, Maria] Univ Bari, Via Calefati 53, I-70122 Bari, Italy, [Izquierdo, Guillermo] Hosp Univ Virgen Macarena, Amador De Los Rios 48-50 4a, Seville 41003, Spain, [Lugaresi, Alessandra] Univ G DAnnunzio, Dept Neurosci Imaging & Clin Sci, Via Vestini, I-66100 Chieti, Italy, [Lugaresi, Alessandra] Univ Bologna, Dept Biomed & Neuromotor Sci, Via Vestini, I-66100 Bologna, Italy, [Girard, Marc] Hop Notre Dame De Bon Secours, 1560 Sherbrooke East, Montreal, PQ H2L 4M1, Canada, [Prat, Alexandre] Hop Notre Dame De Bon Secours, 1560 Sherbrooke East, Montreal, PQ H2L 4M1, Canada, [Duquette, Pierre] Hop Notre Dame De Bon Secours, 1560 Sherbrooke East, Montreal, PQ H2L 4M1, Canada, [Girard, Marc] CHUM, Montreal, PQ, Canada, [Prat, Alexandre] CHUM, Montreal, PQ, Canada, [Duquette, Pierre] CHUM, Montreal, PQ, Canada, [Girard, Marc] Univ Montreal, Montreal, PQ, Canada, [Prat, Alexandre] Univ Montreal, Montreal, PQ, Canada, [Duquette, Pierre] Univ Montreal, Montreal, PQ, Canada, [Grammond, Pierre] Univ Montreal, Montreal, PQ, Canada, [Grammond, Pierre] Ctr Readaptat Deficience Phys Chaudiere Appalache, 9500 Blvd Ctr Hosp, Levis, AB G6X 0A1, Canada, [Sola, Patrizia] Nuovo Osped Civile St Agostino Estense, Via Giardini 1355, I-41100 Modena, Italy, [Hupperts, Raymond] Zuyderland Ziekenhuis, Walramstr 23, NL-6131 BK Sittard, Netherlands, [Grand'Maison, Francois] Neuro Rive Sud, 4896 Boul Taschereau,Suite 250, Greenfield Pk, PQ J4V 2J2, Canada, [Pucci, Eugenio] Azienda Sanitaria Unica Reg Marche AV3, Via Santa Lucia 2, I-62100 Macerata, Italy, [Boz, Cavit] Karadeniz Tech Univ, Farabi Hosp, Med Fac, TR-61080 Trabzon, Turkey, [Alroughani, Raed] Amiri Hosp, POB 1661, Kuwait 73767, Kuwait, [Van Pesch, Vincent] Clin Univ St Luc, Ave Hippocrate,10 UCL10-80, BXL-1200 Brussels, Belgium, [Lechner-Scott, Jeannette] Univ Newcastle, Lookout Rd, Newcastle, NSW 2305, Australia, [Terzi, Murat] Ondokuz Mayis Univ, Fac Med, TR-55160 Kurupelit, Turkey, [Bergamaschi, Roberto] C Mondino Natl Neurol Inst, Via Mondino 2, I-27100 Pavia, Italy, [Iuliano, Gerardo] Osped Riuniti Salerno, Via S Leonardo, I-84100 Salerno, Italy, [Granella, Franco] Univ Parma, Via Gramsci 14, I-43100 Parma, Italy, [Spitaleri, Daniele] Azienda Osped Rilievo Nazl San Giuseppe Moscati A, I-83100 Avellino, Italy, [Shaygannejad, Vahid] Isfahan Univ Med Sci, Soffeh St, Esfahan 81744, Iran, [Oreja-Guevara, Celia] Hosp Univ La Paz, Paseo Castellana 261, Madrid 28050, Spain, [Slee, Mark] Flinders Med Ctr, Flinders Dr, Adelaide, SA 5042, Australia, [Ampapa, Radek] Nemocnice Jihlava, Vrchlickeho 59, Jihlava 58633, Czech Republic, [Verheul, Freek] Groene Hart Ziekenhuis, Bleulandweg 10, NL-2800 BB Gouda, Netherlands, [McCombe, Pamela] Royal Brisbane & Womens Hosp, 33 North St, Spring Hill, Qld 4000, Australia, [Olascoaga, Javier] Hosp Donostia, Paseo Begiristain, San Sebastian 20014, Spain, [Amato, Maria Pia] Univ Florence, Viale Morgagni 85, I-50134 Florence, Italy, [Vucic, Steve] Westmead Hosp, Hawkesbury Rd, Sydney, NSW 2145, Australia, [Hodgkinson, Suzanne] Liverpool Hosp, Elizabeth St,21, Liverpool, SA, Australia, [Ramo-Tello, Cristina] Hosp Germans Trias i Pujol, Crtra Canyet S-N, Badalona 8916, Spain, [Flechter, Shlomo] Assaf Harofeh Med Ctr, IL-70100 Zerifin, Israel, [Cristiano, Edgardo] Hosp Italiano Buenos Aires, Guise 1870, RA-1425 Buenos Aires, DF, Argentina, [Rozsa, Csilla] Jahn Ferenc Teaching Hosp, Koves 1, H-1101 Budapest, Hungary, [Moore, Fraser] Jewish Gen Hosp, 3755 Cote St Catherine, Montreal, PQ J7A 4T8, Canada, [Luis Sanchez-Menoyo, Jose] Hosp Galdakao Usansolo, Barrio Labeaga S-N, Galdakao 48660, Spain, [Laura Saladino, Maria] INEBA Inst Neurosci Buenos Aires, Guardia Vieja 4435,C1192AAW, Buenos Aires, DF, Argentina, [Hillert, Jan] Univ Sydney, Brain & Mind Ctr, 100 Mallett, Camperdown, NSW 2050, Australia, [Butzkueven, Helmut] Monash Univ, Box Hill Hosp, Dept Neurol, Melbourne, Vic, Australia, National Health and Medical Research Council, National Health and Medical Research Council (centre for research excellence), University of Melbourne (Faculty of Medicine, Dentistry and Health Sciences research fellowship), Biogen, Novartis, Merck, Roche, Teva, Sanofi Genzyme, Klinische Neurowetenschappen, MUMC+: MA Med Staf Spec Neurologie (9), and RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience
Subjects: Male, 0301 basic medicine, relapses, Databases, Factual, Failure, disability, multiple sclerosis, precision medicine, prediction, Disability Evaluation, Glatiramer acetate, 0302 clinical medicine, Natalizumab, Recurrence, Risk Factors, Medicine, Relapse, Progression, Precision medicine, Switch, Prognosis, Clinical Trial, Fingolimod, Multicenter Study, Treatment Outcome, Cohort, Disease Progression, Female, Algorithms, Immunosuppressive Agents, medicine.drug, Cohort study, Adult, Registry, medicine.medical_specialty, Multiple Sclerosis, Interferon-beta therapy, External validity, Disability, Multiple sclerosis, Prediction, Relapses, Neurology (clinical), Databases, Young Adult, 03 medical and health sciences, Internal medicine, Journal Article, Humans, Multiple sclerosi, Internal validity, Factual, Disease burden, Demography, business.industry, Prognostic-factors, Reproducibility of Results, Discontinuation, 030104 developmental biology, Physical therapy, business, 030217 neurology & neurosurgery, Forecasting
Abstract: none 47 si Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of disability regression was predominantly associated with pre-baseline disability, therapy and relapse activity. Relapse incidence was associated with pretreatment relapse activity, age and relapsing disease course, with the strength of these associations varying among therapies. Accuracy and internal validity (n = 1196) of the resulting predictive models was high (480%) for relapse incidence during the first year and for disability outcomes, moderate for relapse incidence in Years 2-4 and for the change in the cumulative disease burden, and low for conversion to secondary progressive disease and treatment discontinuation. External validation showed similar results, demonstrating high external validity for disability and relapse outcomes, moderate external validity for cumulative disease burden and low external validity for conversion to secondary progressive disease and treatment discontinuation. We conclude that demographic, clinical and paraclinical information helps predict individual response to disease-modifying therapies at the time of their commencement. none Kalincik, Tomas; Manouchehrinia, Ali; Sobisek, Lukas; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Girard, Marc; Prat, Alexandre; Duquette, Pierre; Grammond, Pierre; Sola, Patrizia; Hupperts, Raymond; Grand'Maison, Francois; Pucci, Eugenio; Boz, Cavit; Alroughani, Raed; Van Pesch, Vincent; Lechner-scott, Jeannette; Terzi, Murat; Bergamaschi, Roberto; Iuliano, Gerardo; Granella, Franco; Spitaleri, Daniele; Shaygannejad, Vahid; Oreja-guevara, Celia; Slee, Mark; Ampapa, Radek; Verheul, Freek; Mccombe, Pamela; Olascoaga, Javier; Amato, Maria Pia; Vucic, Steve; Hodgkinson, Suzanne; Ramo-tello, Cristina; Flechter, Shlomo; Cristiano, Edgardo; Rozsa, Csilla; Moore, Fraser; Sanchez-menoyo, Jose Luis; Saladino, Maria Laura; Barnett, Michael; Hillert, Jan; Butzkueven, Helmut Kalincik, Tomas; Manouchehrinia, Ali; Sobisek, Lukas; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Girard, Marc; Prat, Alexandre; Duquette, Pierre; Grammond, Pierre; Sola, Patrizia; Hupperts, Raymond; Grand'Maison, Francois; Pucci, Eugenio; Boz, Cavit; Alroughani, Raed; Van Pesch, Vincent; Lechner-scott, Jeannette; Terzi, Murat; Bergamaschi, Roberto; Iuliano, Gerardo; Granella, Franco; Spitaleri, Daniele; Shaygannejad, Vahid; Oreja-guevara, Celia; Slee, Mark; Ampapa, Radek; Verheul, Freek; Mccombe, Pamela; Olascoaga, Javier; Amato, Maria Pia; Vucic, Steve; Hodgkinson, Suzanne; Ramo-tello, Cristina; Flechter, Shlomo; Cristiano, Edgardo; Rozsa, Csilla; Moore, Fraser; Sanchez-menoyo, Jose Luis; Saladino, Maria Laura; Barnett, Michael; Hillert, Jan; Butzkueven, Helmut
Published: 2017

15. Is It Time for Ocrelizumab Extended Interval Dosing in Relapsing Remitting MS? Evidence from An Italian Multicenter Experience During the COVID-19 Pandemic

Author: Aurora Zanghì, Carlo Avolio, Elisabetta Signoriello, Gianmarco Abbadessa, Maria Cellerino, Diana Ferraro, Christian Messina, Stefania Barone, Graziella Callari, Elena Tsantes, Patrizia Sola, Paola Valentino, Franco Granella, Francesco Patti, Giacomo Lus, Simona Bonavita, Matilde Inglese, Emanuele D’Amico, Zanghì, Aurora, Avolio, Carlo, Signoriello, Elisabetta, Abbadessa, Gianmarco, Cellerino, Maria, Ferraro, Diana, Messina, Christian, Barone, Stefania, Callari, Graziella, Tsantes, Elena, Sola, Patrizia, Valentino, Paola, Granella, Franco, Patti, Francesco, Lus, Giacomo, Bonavita, Simona, Inglese, Matilde, and D'Amico, Emanuele
Subjects: Pharmacology, Multiple Sclerosis, Pandemic, COVID-19, Gadolinium, Extended interval dosing, Standard interval dosing, Cytidine Diphosphate, Immunologic Factor, Multiple Sclerosis, Relapsing-Remitting, Recurrence, Humans, Immunologic Factors, Pharmacology (medical), Disease activity, Ocrelizumab, Neurology (clinical), Pandemics, Sudden Infant Death, MRI, Human
Abstract: In the COVID-19 pandemic era, safety concerns have been raised regarding the risk of severe infection following administration of ocrelizumab (OCR), a B-cell-depleting therapy. We enrolled all relapsing remitting multiple sclerosis (RRMS) patients who received maintenance doses of OCR from January 2020 to June 2021. Data were extracted in December 2021. Standard interval dosing (SID) was defined as a regular maintenance interval of OCR infusion every 6 months, whereas extended interval dosing (EID) was defined as an OCR infusion delay of at least 4 weeks. Three infusions were considered in defining SID vs. EID (infusions A, B, and C). Infusion A was the last infusion before January 2020. The primary study outcome was a comparison of disease activity during the A-C interval, which was defined as either clinical (new relapses) or radiological (new lesions on T1-gadolinium or T2-weighted magnetic resonance imaging (MRI) sequences). Second, we aimed to assess confirmed disability progression (CDP). A total cohort of 278 patients (174 on SID and 104 on EID) was enrolled. Patients who received OCR on EID had a longer disease duration and a higher rate of vaccination against severe acute respiratory syndrome-coronavirus 2 (p
Published: 2022

16. Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis

Author: Ibrahima Diouf, Charles B. Malpas, Sifat Sharmin, Izanne Roos, Dana Horakova, Eva Kubala Havrdova, Francesco Patti, Vahid Shaygannejad, Serkan Ozakbas, Guillermo Izquierdo, Sara Eichau, Marco Onofrj, Alessandra Lugaresi, Raed Alroughani, Alexandre Prat, Marc Girard, Pierre Duquette, Murat Terzi, Cavit Boz, Francois Grand'Maison, Sherif Hamdy, Patrizia Sola, Diana Ferraro, Pierre Grammond, Recai Turkoglu, Katherine Buzzard, Olga Skibina, Bassem Yamout, Ayse Altintas, Oliver Gerlach, Vincent van Pesch, Yolanda Blanco, Davide Maimone, Jeannette Lechner‐Scott, Roberto Bergamaschi, Rana Karabudak, Gerardo Iuliano, Chris McGuigan, Elisabetta Cartechini, Michael Barnett, Stella Hughes, Maria José Sa, Claudio Solaro, Ludwig Kappos, Cristina Ramo‐Tello, Edgardo Cristiano, Suzanne Hodgkinson, Daniele Spitaleri, Aysun Soysal, Thor Petersen, Mark Slee, Ernest Butler, Franco Granella, Koen de Gans, Pamela McCombe, Radek Ampapa, Bart Van Wijmeersch, Anneke van der Walt, Helmut Butzkueven, Julie Prevost, L. G. F. Sinnige, Jose Luis Sanchez‐Menoyo, Steve Vucic, Guy Laureys, Liesbeth Van Hijfte, Dheeraj Khurana, Richard Macdonell, Riadh Gouider, Tamara Castillo‐Triviño, Orla Gray, Eduardo Aguera‐Morales, Abdullah Al‐Asmi, Cameron Shaw, Norma Deri, Talal Al‐Harbi, Yara Fragoso, Tunde Csepany, Angel Perez Sempere, Irene Trevino‐Frenk, Jan Schepel, Fraser Moore, Tomas Kalincik, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Laureys, Guy/0000-0002-1708-4373, Lugaresi, Alessandra/0000-0003-2902-5589, Aguera-Morales, Eduardo/0000-0002-8604-2054, Petersen, Thor/0000-0001-5633-2600, Roos, Izanne/0000-0003-0371-3666, Slee, Mark/0000-0003-4323-2453, patti, francesco/0000-0002-6923-0846, Diouf, Ibrahima, Malpas, Charles B., Sharmin , Sifat, Roos, Izanne, Horakova, Dana, Havrdova, Eva Kubala, Patti, Francesco, Shaygannejad, Vahid, Ozakbas, Serkan, Izquierdo, Guillermo, Eichau, Sara, Onofrj, Marco, Lugaresi, Alessandra, Alroughani, Raed, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Terzi, Murat, Boz, Cavit, Grand'Maison, Francois, Hamdy, Sherif, Sola, Patrizia, Ferraro, Diana, Grammond, Pierre, Turkoglu, Recai, Buzzard, Katherine, Skibina, Olga, Yamout, Bassem, Altintas, Ayse, Gerlach, Oliver, van Pesch, Vincent, Blanco, Yolanda, Maimone, Davide, Lechner-Scott, Jeannette, Bergamaschi, Roberto, Karabudak, Rana, Iuliano, Gerardo, McGuigan, Chris, Cartechini, Elisabetta, Barnett, Michael, Hughes, Stella, Sa, Maria Jose, Solaro, Claudio, Kappos, Ludwig, Ramo-Tello, Cristina, Cristiano, Edgardo, Hodgkinson, Suzanne, Spitaleri, Daniele, Soysal, Aysun, Petersen, Thor, Slee, Mark, Butler, Ernest, Granella, Franco, de Gans, Koen, McCombe, Pamela, Ampapa, Radek, VAN WIJMEERSCH, Bart, van der Walt, Anneke, Butzkueven, Helmut, Prevost, Julie, Sinnige, L. G. F., Sanchez-Menoyo, Jose Luis, Vucic, Steve, Laureys, Guy, Van Hijfte, Liesbeth, Khurana, Dheeraj, Macdonell, Richard, Gouider, Riadh, Castillo-Trivino, Tamara, Gray, Orla, Aguera-Morales, Eduardo, Al-Asmi, Abdullah, Shaw, Cameron, Deri, Norma, Al-Harbi, Talal, Fragoso, Yara, Csepany, Tunde, Sempere, Angel Perez, Trevino-Frenk, Irene, Schepel, Jan, Moore, Fraser, and Kalincik, Tomas
Subjects: marginal structural model, relapse, Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive, multiple sclerosis, Multiple Sclerosis, Relapsing-Remitting, Neurology, Recurrence, Medicine and Health Sciences, Humans, Neurology (clinical), EDSS, immunotherapy, Proportional Hazards Models
Abstract: Background and purpose: This study assessed the effect of patient characteristics on the response to disease-modifying therapy (DMT) in multiple sclerosis (MS).Methods: We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow -up >= 1 year, and Expanded Disability Status Scale (EDSS) score >= 3, with >= 1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12 -month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics.Results: Among 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.45- 0.60), 46% lower risk of disability worsening (HR = 0.54, 95% CI = 0.41- 0.71), and 32% greater chance of disability improvement (HR = 1.32, 95% CI = 1.09- 1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity.Conclusions: DMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age. This study was financially supported by the National Health and Medical Research Council of Australia (1129189, 1140766, 1080518) We thank the patients and their carers who have agreed to participate in the global MSBase cohort study. The MSBase Foundation is a not-for-profit organization that receives support from Roche, Merck, Biogen, Novartis, Bayer-Schering, Sanofi-Genzyme, and Teva. The study was conducted separately and apart from the guidance of the sponsors. Open access publishing facilitated by The University of Melbourne, as part of the Wiley - The University of Melbourne agreement via the Council of Australian University Librarians.
Published: 2023

17. Progression is independent of relapse activity in early multiple sclerosis: a real-life cohort study

Author: Emilio Portaccio, Angelo Bellinvia, Mattia Fonderico, Luisa Pastò, Lorenzo Razzolini, Rocco Totaro, Daniele Spitaleri, Alessandra Lugaresi, Eleonora Cocco, Marco Onofrj, Franco Di Palma, Francesco Patti, Davide Maimone, Paola Valentino, Paolo Confalonieri, Alessandra Protti, Patrizia Sola, Giacomo Lus, Giorgia Teresa Maniscalco, Vincenzo Brescia Morra, Giuseppe Salemi, Franco Granella, Ilaria Pesci, Roberto Bergamaschi, Umberto Aguglia, Marika Vianello, Marta Simone, Vito Lepore, Pietro Iaffaldano, Massimo Filippi, Maria Trojano, Maria Pia Amato, Portaccio, Emilio, Bellinvia, Angelo, Fonderico, Mattia, Pastò, Luisa, Razzolini, Lorenzo, Totaro, Rocco, Spitaleri, Daniele, Lugaresi, Alessandra, Cocco, Eleonora, Onofrj, Marco, Di Palma, Franco, Patti, Francesco, Maimone, Davide, Valentino, Paola, Confalonieri, Paolo, Protti, Alessandra, Sola, Patrizia, Lus, Giacomo, Maniscalco, Giorgia Teresa, Brescia Morra, Vincenzo, Salemi, Giuseppe, Granella, Franco, Pesci, Ilaria, Bergamaschi, Roberto, Aguglia, Umberto, Vianello, Marika, Simone, Marta, Lepore, Vito, Iaffaldano, Pietro, Filippi, Massimo, Trojano, Maria, and Amato, Maria Pia
Subjects: Multiple Sclerosis, relapse-associated worsening, progression independent of relapse activity, relapsing multiple sclerosis, Cohort Studies, Multiple Sclerosis, Relapsing-Remitting, relapse associated worsening, Recurrence, Chronic Disease, Disease Progression, Humans, Settore MED/26 - Neurologia, Neurology (clinical), Retrospective Studies
Abstract: Portaccio et al. report that in early relapsing-onset multiple sclerosis, progression independent of relapse activity is an important contributor to disability accumulation. Insidious progression occurs even in the earliest disease phases, suggesting that inflammation and degeneration may represent a single disease continuum.Disability accrual in multiple sclerosis may occur as relapse-associated worsening or progression independent of relapse activity. The role of progression independent of relapse activity in early multiple sclerosis is yet to be established. The objective of this multicentre, observational, retrospective cohort study was to investigate the contribution of relapse-associated worsening and progression independent of relapse activity to confirmed disability accumulation in patients with clinically isolated syndrome and early relapsing-remitting multiple sclerosis, assessed within one year from onset and with follow-up >= 5 years (n = 5169). Data were extracted from the Italian Multiple Sclerosis Register. Confirmed disability accumulation was defined by an increase in Expanded Disability Status Scale score confirmed at 6 months, and classified per temporal association with relapses. Factors associated with progression independent of relapse activity and relapse-associated worsening were assessed using multivariable Cox regression models. Over a follow-up period of 11.5 +/- 5.5 years, progression independent of relapse activity occurred in 1427 (27.6%) and relapse-associated worsening in 922 (17.8%) patients. Progression independent of relapse activity was associated with older age at baseline [hazard ratio (HR) = 1.19; 95% confidence interval (CI) 1.13-1.25, P < 0.001], having a relapsing-remitting course at baseline (HR = 1.44; 95% CI 1.28-1.61, P < 0.001), longer disease duration at baseline (HR = 1.56; 95% CI 1.28-1.90, P < 0.001), lower Expanded Disability Status Scale at baseline (HR = 0.92; 95% CI 0.88-0.96, P < 0.001) and lower number of relapses before the event (HR = 0.76; 95% CI 0.73-0.80, P < 0.001). Relapse-associated worsening was associated with younger age at baseline (HR = 0.87; 95% CI 0.81-0.93, P < 0.001), having a relapsing-remitting course at baseline (HR = 1.55; 95% CI 1.35-1.79, P < 0.001), lower Expanded Disability Status Scale at baseline (HR = 0.94; 95% CI 0.89-0.99, P = 0.017) and a higher number of relapses before the event (HR = 1.04; 95% CI 1.01-1.07, P < 0.001). Longer exposure to disease-modifying drugs was associated with a lower risk of both progression independent of relapse activity and relapse-associated worsening (P < 0.001). This study provides evidence that in an early relapsing-onset multiple sclerosis cohort, progression independent of relapse activity was an important contributor to confirmed disability accumulation. Our findings indicate that insidious progression appears even in the earliest phases of the disease, suggesting that inflammation and neurodegeneration can represent a single disease continuum, in which age is one of the main determinants of disease phenomenology.
Published: 2022

18. Towards a validated definition of the clinical transition to secondary progressive multiple sclerosis: A study from the Italian MS Register

Author: Pietro Iaffaldano, Giuseppe Lucisano, Tommaso Guerra, Francesco Patti, Marco Onofrj, Vincenzo Brescia Morra, Mauro Zaffaroni, Carlo Pozzilli, Eleonora Cocco, Patrizia Sola, Giuseppe Salemi, Matilde Inglese, Roberto Bergamaschi, Claudio Gasperini, Antonella Conte, Marco Salvetti, Giacomo Lus, Giorgia Teresa Maniscalco, Rocco Totaro, Marika Vianello, Franco Granella, Elisabetta Ferraro, Umberto Aguglia, Maurizia Gatto, Francesca Sangalli, Clara Grazia Chisari, Giovanna De Luca, Antonio Carotenuto, Damiano Baroncini, Delia Colombo, Mihaela Nica, Damiano Paolicelli, Giancarlo Comi, Massimo Filippi, Maria Pia Amato, Maria Trojano, Iaffaldano, Pietro, Lucisano, Giuseppe, Guerra, Tommaso, Patti, Francesco, Onofrj, Marco, Brescia Morra, Vincenzo, Zaffaroni, Mauro, Pozzilli, Carlo, Cocco, Eleonora, Sola, Patrizia, Salemi, Giuseppe, Inglese, Matilde, Bergamaschi, Roberto, Gasperini, Claudio, Conte, Antonella, Salvetti, Marco, Lus, Giacomo, Maniscalco, Giorgia Teresa, Totaro, Rocco, Vianello, Marika, Granella, Franco, Ferraro, Elisabetta, Aguglia, Umberto, Gatto, Maurizia, Sangalli, Francesca, Chisari, Clara Grazia, De Luca, Giovanna, Carotenuto, Antonio, Baroncini, Damiano, Colombo, Delia, Nica, Mihaela, Paolicelli, Damiano, Comi, Giancarlo, Filippi, Massimo, Amato, Maria Pia, and Trojano, Maria
Subjects: Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive, Multiple sclerosis, Multiple Sclerosis, Relapsing-Remitting, Neurology, big data, Area Under Curve, data-driven algorithm, disease registry, secondary progressive, Humans, Settore MED/26 - Neurologia, Neurology (clinical), prognosis
Abstract: Background: Definitions for reliable identification of transition from relapsing-remitting multiple sclerosis (MS) to secondary progressive (SP)MS in clinical cohorts are not available. Objectives: To compare diagnostic performances of two different data-driven SPMS definitions. Methods: Data-driven SPMS definitions based on a version of Lorscheider’s algorithm (DDA) and on the EXPAND trial inclusion criteria were compared, using the neurologist’s definition (ND) as gold standard, in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Akaike information criterion (AIC) and area under the curve (AUC). Results: A cohort of 10,240 MS patients with ⩾5 years of follow-up was extracted from the Italian MS Registry; 880 (8.5%) patients were classified as SPMS according to the neurologist definition, 1806 (17.6%) applying the DDA and 1134 (11.0%) with the EXPAND definition. The DDA showed greater discrimination power (AUC: 0.8 vs 0.6) and a higher sensitivity (77.1% vs 38.0%) than the EXPAND definition, with similar specificity (88.0% vs 91.5%). PPV and NPV were higher using the DDA than considering EXPAND definition (37.5% vs 29.5%; 97.6% vs 94.0%). Conclusion: Data-driven definitions demonstrated greater ability to capture SP transition than neurologist’s definition and the global accuracy of DDA seems to be higher than the EXPAND definition.
Published: 2022

19. Confirmed disability progression as a marker of permanent disability in multiple sclerosis

Author: Sifat Sharmin, Francesca Bovis, Charles Malpas, Dana Horakova, Eva Kubala Havrdova, Guillermo Izquierdo, Sara Eichau, Maria Trojano, Alexandre Prat, Marc Girard, Pierre Duquette, Marco Onofrj, Alessandra Lugaresi, Francois Grand'Maison, Pierre Grammond, Patrizia Sola, Diana Ferraro, Murat Terzi, Oliver Gerlach, Raed Alroughani, Cavit Boz, Vahid Shaygannejad, Vincent van Pesch, Elisabetta Cartechini, Ludwig Kappos, Jeannette Lechner‐Scott, Roberto Bergamaschi, Recai Turkoglu, Claudio Solaro, Gerardo Iuliano, Franco Granella, Bart Van Wijmeersch, Daniele Spitaleri, Mark Slee, Pamela McCombe, Julie Prevost, Radek Ampapa, Serkan Ozakbas, Jose Luis Sanchez‐Menoyo, Aysun Soysal, Steve Vucic, Thor Petersen, Koen de Gans, Ernest Butler, Suzanne Hodgkinson, Youssef Sidhom, Riadh Gouider, Edgardo Cristiano, Tamara Castillo‐Triviño, Maria Laura Saladino, Michael Barnett, Fraser Moore, Csilla Rozsa, Bassem Yamout, Olga Skibina, Anneke van der Walt, Katherine Buzzard, Orla Gray, Stella Hughes, Angel Perez Sempere, Bhim Singhal, Yara Fragoso, Cameron Shaw, Allan Kermode, Bruce Taylor, Magdolna Simo, Neil Shuey, Talal Al‐Harbi, Richard Macdonell, Jose Andres Dominguez, Tunde Csepany, Carmen Adella Sirbu, Maria Pia Sormani, Helmut Butzkueven, Tomas Kalincik, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de biochimie médicale, UCL - (SLuc) Service de neurologie, Sirbu, Carmen Adella/0000-0002-1982-1066, Malpas, Charles/0000-0003-0534-3718, Sharmin, Sifat, Bovis, Francesca, Malpas, Charle, Horakova, Dana, Havrdova, Eva Kubala, Izquierdo, Guillermo, Eichau, Sara, Trojano, Maria, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Onofrj, Marco, Lugaresi, Alessandra, Grand'Maison, Francoi, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Terzi, Murat, Gerlach, Oliver, Alroughani, Raed, Boz, Cavit, Shaygannejad, Vahid, van Pesch, Vincent, Cartechini, Elisabetta, Kappos, Ludwig, Lechner-Scott, Jeannette, Bergamaschi, Roberto, Turkoglu, Recai, Solaro, Claudio, Iuliano, Gerardo, Granella, Franco, Van Wijmeersch, Bart, Spitaleri, Daniele, Slee, Mark, McCombe, Pamela, Prevost, Julie, Ampapa, Radek, Ozakbas, Serkan, Sanchez-Menoyo, Jose Lui, Soysal, Aysun, Vucic, Steve, Petersen, Thor, de Gans, Koen, Butler, Ernest, Hodgkinson, Suzanne, Sidhom, Youssef, Gouider, Riadh, Cristiano, Edgardo, Castillo-Triviño, Tamara, Saladino, Maria Laura, Barnett, Michael, Moore, Fraser, Rozsa, Csilla, Yamout, Bassem, Skibina, Olga, van der Walt, Anneke, Buzzard, Katherine, Gray, Orla, Hughes, Stella, Sempere, Angel Perez, Singhal, Bhim, Fragoso, Yara, Shaw, Cameron, Kermode, Allan, Taylor, Bruce, Simo, Magdolna, Shuey, Neil, Al-Harbi, Talal, Macdonell, Richard, Dominguez, Jose Andre, Csepany, Tunde, Sirbu, Carmen Adella, Sormani, Maria Pia, Butzkueven, Helmut, and Kalincik, Tomas
Subjects: Male, risk scoring, sustained disability progression, Multiple Sclerosis, CLARITY, clinical trial, functional system impairment, Cohort Studies, Disability Evaluation, Multiple Sclerosis, Relapsing-Remitting, Neurology, Disease Progression, Cladribine, Humans, Female, Neurology (clinical), Randomized Controlled Trials as Topic
Abstract: Background and purpose The prevention of disability over the long term is the main treatment goal in multiple sclerosis (MS); however, randomized clinical trials evaluate only short-term treatment effects on disability. This study aimed to define criteria for 6-month confirmed disability progression events of MS with a high probability of resulting in sustained long-term disability worsening. Methods In total, 14,802 6-month confirmed disability progression events were identified in 8741 patients from the global MSBase registry. For each 6-month confirmed progression event (13,321 in the development and 1481 in the validation cohort), a sustained progression score was calculated based on the demographic and clinical characteristics at the time of progression that were predictive of long-term disability worsening. The score was externally validated in the Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) trial. Results The score was based on age, sex, MS phenotype, relapse activity, disability score and its change from baseline, number of affected functional system domains and worsening in six of the domains. In the internal validation cohort, a 61% lower chance of improvement was estimated with each unit increase in the score (hazard ratio 0.39, 95% confidence interval 0.29-0.52; discriminatory index 0.89). The proportions of progression events sustained at 5 years stratified by the score were 1: 72%; 2: 88%; 3: 94%; 4: 100%. The results of the CLARITY trial were confirmed for reduction of disability progression that was >88% likely to be sustained (events with score >1.5). Conclusions Clinicodemographic characteristics of 6-month confirmed disability progression events identify those at high risk of sustained long-term disability. This knowledge will allow future trials to better assess the effect of therapy on long-term disability accrual. NHMRC [1129189, 1157717, 1140766]; Merck; Biogen; Novartis; Roche; Bayer; Schering; Sanofi Genzyme; Teva Pharmaceutical Industries
Published: 2022

20. Risk of Getting COVID-19 in People With Multiple Sclerosis: A Case-Control Study

Author: Pietro Iaffaldano, Giuseppe Lucisano, Alessia Manni, Damiano Paolicelli, Francesco Patti, Marco Capobianco, Vincenzo Brescia Morra, Patrizia Sola, Ilaria Pesci, Giacomo Lus, Giovanna De Luca, Alessandra Lugaresi, Paola Cavalla, Sara Montepietra, Giorgia Teresa Maniscalco, Franco Granella, Paolo Ragonese, Marika Vianello, Laura Brambilla, Rocco Totaro, Simona Toscano, Simona Malucchi, Maria Petracca, Lucia Moiola, Diana Ferraro, Vito Lepore, Paola Mosconi, Michela Ponzio, Gioacchino Tedeschi, Giancarlo Comi, Mario Alberto Battaglia, Massimo Filippi, Maria Pia Amato, Maria Trojano, Iaffaldano, Pietro, Lucisano, Giuseppe, Manni, Alessia, Paolicelli, Damiano, Patti, Francesco, Capobianco, Marco, Brescia Morra, Vincenzo, Sola, Patrizia, Pesci, Ilaria, Lus, Giacomo, De Luca, Giovanna, Lugaresi, Alessandra, Cavalla, Paola, Montepietra, Sara, Maniscalco, Giorgia Teresa, Granella, Franco, Ragonese, Paolo, Vianello, Marika, Brambilla, Laura, Totaro, Rocco, Toscano, Simona, Malucchi, Simona, Petracca, Maria, Moiola, Lucia, Ferraro, Diana, Lepore, Vito, Mosconi, Paola, Ponzio, Michela, Tedeschi, Gioacchino, Comi, Giancarlo, Battaglia, Mario Alberto, Filippi, Massimo, Amato, Maria Pia, and Trojano, Maria
Subjects: Adult, Male, Multiple Sclerosis, Time Factors, Dimethyl Fumarate, Sex Factor, Relapsing-Remitting, Severity of Illness Index, Article, Immunosuppressive Agent, Sex Factors, Multiple Sclerosis, Relapsing-Remitting, Risk Factors, Multiple Sclerosi, Odds Ratio, Humans, Age Factor, g COVID-19, Fingolimod Hydrochloride, SARS-CoV-2, Natalizumab, Risk Factor, Age Factors, COVID-19, Glatiramer Acetate, Interferon-beta, Middle Aged, Multiple Sclerosis, Chronic Progressive, Chronic Progressive, Neurology, Italy, Case-Control Studies, Female, Immunosuppressive Agents, Neurology (clinical), Case-Control Studie, Human
Abstract: Background and ObjectivesSeveral studies have assessed risk factors associated with the severity of COVID-19 outcomes in people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies (DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection has not been evaluated so far. The objective of this study was to assess risk factors of contracting SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR).MethodsA case-control (1:2) study was set up. Cases included PwMS with a confirmed diagnosis of COVID-19, and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity score–matched by the date of COVID-19 diagnosis, the date of last visit, and the region of residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The impact of DMTs was assessed in 3 independent logistic regression models including one of the following covariates: last administered DMT, previous DMT sequences, or the place where the last treatment was administered.ResultsA total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly associated (p < 0.02) with a higher risk of contracting COVID-19. Patients receiving natalizumab as last DMT (OR [95% CI]: 2.38 [1.66–3.42], p < 0.0001) and those who underwent an escalation treatment strategy (1.57 [1.16–2.13], p = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring hospital access (1.65 [1.34–2.04], p < 0.0001) showed a significant higher risk than those taking self-administered DMTs at home.DiscussionThis case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS.Classification of EvidenceThis study provides Class III evidence that among patients with MS, younger age, being female individuals, having more comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an interferon beta agent was protective.
Published: 2022

21. Comparing Natural History of Early and Late Onset Pediatric Multiple Sclerosis

Author: Ermelinda De Meo, Massimo Filippi, Maria Trojano, Giancarlo Comi, Francasco Patti, Vincenzo Brescia Morra, Giuseppe Salemi, Marco Onofrj, Giacomo Lus, Eleonora Cocco, Mattia Fonderico, Valentina Torri Clerici, Giorgia Teresa Maniscalco, Paola Valentino, Antonio Bertolotto, Alessandra Lugaresi, Roberto Bergamaschi, Marco Rovaris, Patrizia Sola, Gioacchino Tedeschi, Ilaria Pesci, Umberto Aguglia, Paola Cavalla, Davide Maimone, Franco Granella, Marika Vianello, Marta Simone, Emilio Portaccio, Maria Pia Amato, De Meo, E., Filippi, M., Trojano, M., Comi, G., Patti, F., Brescia Morra, V., Salemi, G., Onofrj, M., Lus, G., Cocco, E., Fonderico, M., Torri Clerici, V., Maniscalco, G. T., Valentino, P., Bertolotto, A., Lugaresi, A., Bergamaschi, R., Rovaris, M., Sola, P., Tedeschi, G., Pesci, I., Aguglia, U., Cavalla, P., Maimone, D., Granella, F., Vianello, M., Simone, M., Portaccio, E., Amato, M. P., De Meo, Ermelinda, Filippi, Massimo, Trojano, Maria, Comi, Giancarlo, Patti, Francasco, Brescia Morra, Vincenzo, Salemi, Giuseppe, Onofrj, Marco, Lus, Giacomo, Cocco, Eleonora, Fonderico, Mattia, Torri Clerici, Valentina, Maniscalco, Giorgia Teresa, Valentino, Paola, Bertolotto, Antonio, Lugaresi, Alessandra, Bergamaschi, Roberto, Rovaris, Marco, Sola, Patrizia, Tedeschi, Gioacchino, Pesci, Ilaria, Aguglia, Umberto, Cavalla, Paola, Maimone, Davide, Granella, Franco, Vianello, Marika, Simone, Marta, Portaccio, Emilio, Amato, Maria Pia, De Meo, E, Filippi, M, Trojano, M, Comi, G, Patti, F, Brescia Morra, V, Salemi, G, Onofrj, M, Lus, G, Cocco, E, Fonderico, M, Torri Clerici, V, Maniscalco, Gt, Valentino, P, Bertolotto, A, Lugaresi, A, Bergamaschi, R, Rovaris, M, Sola, P, Tedeschi, G, Pesci, I, Aguglia, U, Cavalla, P, Maimone, D, Granella, F, Vianello, M, Simone, M, Portaccio, E, and Amato, Mp
Subjects: Male, Natural History of Multiple Sclerosis, Multiple Sclerosis, Neurology, Recurrence, Pediatric Multiple Sclerosis, Disease Progression, Humans, Disabled Persons, Settore MED/26 - Neurologia, Neurology (clinical), Child, Prognosis
Abstract: Objective: This study was undertaken to describe and compare disease course and prognosis of early (ie, disease onset before age 11 years) and late (ie, disease onset after age 11 years) onset pediatric multiple sclerosis. Methods: Prospectively collected clinical information from Italian Multiple Sclerosis Register of 1993 pediatric multiple sclerosis patients, of whom 172 had early onset, was analyzed. Cox models adjusted for sex, baseline Expanded Disability Status Scale score, and disease-modifying treatments and stratified for diagnostic criteria adopted (Poser vs McDonald) were used to assess the risk of reaching irreversible Expanded Disability Status Scale scores of 3, 4, and 6, and conversion to secondary progressive phenotype in early versus late onset pediatric patients. Prognostic factors were also evaluated. Results: A greater proportion of males, isolated brainstem involvement, and longer time interval between first and second clinical episode were observed in early versus late onset pediatric patients. Compared to late onset, early onset pediatric patients took longer from disease onset to convert to secondary progressive phenotype and to reach all disability milestones. Recovery from first demyelinating event, time to first relapse, annualized relapse rate during the first 3 years of disease, and disease-modifying treatment exposure were independent predictors for long-term disability in early onset pediatric patients. In late onset pediatric patients, isolated optic neuritis, multifocal symptoms, and progressive course at disease onset were additional predictors for long-term disability. Interpretation: These findings point toward the existence of a different natural history in early versus late onset pediatric multiple sclerosis patients. ANN NEUROL 2022.
Published: 2022

22. Disease-Modifying Treatments and Time to Loss of Ambulatory Function in Patients with Primary Progressive Multiple Sclerosis

Author: Emilio, Portaccio, Mattia, Fonderico, Pietro, Iaffaldano, Luisa, Pastò, Lorenzo, Razzolini, Angelo, Bellinvia, Giovanna, De Luca, Paolo, Ragonese, Francesco, Patti, Vincenzo, Brescia Morra, Eleonora, Cocco, Patrizia, Sola, Matilde, Inglese, Giacomo, Lus, Carlo, Pozzilli, Davide, Maimone, Alessandra, Lugaresi, Paola, Gazzola, Giancarlo, Comi, Ilaria, Pesci, Daniele, Spitaleri, Marta, Rezzonico, Marika, Vianello, Carlo, Avolio, Francesco O, Logullo, Franco, Granella, Marco, Salvetti, Mauro, Zaffaroni, Giuseppe, Lucisano, Massimo, Filippi, Maria, Trojano, Maria Pia, Amato, Alessandra, Protti, Portaccio, E, Fonderico, M, Iaffaldano, P, Pasto, L, Razzolini, L, Bellinvia, A, De Luca, G, Ragonese, P, Patti, F, Brescia Morra, V, Cocco, E, Sola, P, Inglese, M, Lus, G, Pozzilli, C, Maimone, D, Lugaresi, A, Gazzola, P, Comi, G, Pesci, I, Spitaleri, D, Rezzonico, M, Vianello, M, Avolio, C, Logullo, F, Granella, F, Salvetti, M, Zaffaroni, M, Lucisano, G, Filippi, M, Trojano, M, Amato, M, Cavaletti, G, Portaccio, Emilio, Fonderico, Mattia, Iaffaldano, Pietro, Pastò, Luisa, Razzolini, Lorenzo, Bellinvia, Angelo, De Luca, Giovanna, Ragonese, Paolo, Patti, Francesco, Brescia Morra, Vincenzo, Cocco, Eleonora, Sola, Patrizia, Inglese, Matilde, Lus, Giacomo, Pozzilli, Carlo, Maimone, Davide, Lugaresi, Alessandra, Gazzola, Paola, Comi, Giancarlo, Pesci, Ilaria, Spitaleri, Daniele, Rezzonico, Marta, Vianello, Marika, Avolio, Carlo, Logullo, Francesco O, Granella, Franco, Salvetti, Marco, Zaffaroni, Mauro, Lucisano, Giuseppe, Filippi, Massimo, Trojano, Maria, and Amato, Maria Pia
Subjects: Adult, Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Recurrence, Retrospective Studie, Multiple Sclerosi, Disease Progression, Humans, Female, Neurology (clinical), Multiple Sclerosis, Chronic Progressive, Retrospective Studies, Human
Abstract: Importance: Except for ocrelizumab, treatment options in primary progressive multiple sclerosis (PPMS) are lacking. Objective: To investigate the effectiveness of DMTs on the risk of becoming wheelchair dependent in a real-world population of patients with PPMS. Design, Setting, and Participants: This was a multicenter, observational, retrospective, comparative effectiveness research study. Data were extracted on November 28, 2018, from the Italian multiple sclerosis register and analyzed from June to December 2021. Mean study follow-up was 11 years. Included in the study cohort were patients with a diagnosis of PPMS and at least 3 years of Expanded Disability Status Scale (EDSS) evaluations and 3 years of follow-up. Main Outcomes and Measures: The risk of reaching an EDSS score of 7.0 was assessed through multivariable Cox regression models. Exposures: Patients who received DMT before the outcome were considered treated. DMT was assessed as a time-dependent variable and by class of DMT (moderately and highly effective). Results: From a total of 3298 patients with PPMS, 2633 were excluded because they did not meet the entry criteria for the phase 3, multicenter, randomized, parallel-group, double-blind, placebo-controlled study to evaluate the efficacy and safety of ocrelizumab in adults with PPMS (ORATORIO) trial. Among the remaining 665 patients (mean [SD] age, 43.0 [10.7] years; 366 female patients [55.0%]), 409 were further selected for propensity score matching (288 treated and 121 untreated patients). In the matched cohort, during the study follow-up, 37% of patients (152 of 409) reached an EDSS score of 7.0 after a mean (SD) follow-up of 10.6 (5.6) years. A higher EDSS score at baseline (adjusted hazard ratio [aHR], 1.32; 95% CI, 1.13-1.55; P
Published: 2022

23. PML risk is the main factor driving the choice of discontinuing natalizumab in a large multiple sclerosis population: results from an Italian multicenter retrospective study

Author: Clara G, Chisari, Giancarlo, Comi, Massimo, Filippi, Damiano, Paolicelli, Pietro, Iaffaldano, Mauro, Zaffaroni, Vincenzo, Brescia Morra, Eleonora, Cocco, Girolama Alessandra, Marfia, Luigi Maria, Grimaldi, Matilde, Inglese, Simona, Bonavita, Alessandra, Lugaresi, Giuseppe, Salemi, Giovanna, De Luca, Salvatore, Cottone, Antonella, Conte, Patrizia, Sola, Umberto, Aguglia, Giorgia Teresa, Maniscalco, Claudio, Gasperini, Maria Teresa, Ferrò, Ilaria, Pesci, Maria Pia, Amato, Marco, Rovaris, Claudio, Solaro, Giacomo, Lus, Davide, Maimone, Roberto, Bergamaschi, Franco, Granella, Alessia, Di Sapio, Antonio, Bertolotto, Rocco, Totaro, Marika, Vianello, Paola, Cavalla, Paolo, Bellantonio, Vito, Lepore, Francesco, Patti, Simonetta, Venturi, Chisari, Clara G, Comi, Giancarlo, Filippi, Massimo, Paolicelli, Damiano, Iaffaldano, Pietro, Zaffaroni, Mauro, Brescia Morra, Vincenzo, Cocco, Eleonora, Marfia, Girolama Alessandra, Grimaldi, Luigi Maria, Inglese, Matilde, Bonavita, Simona, Lugaresi, Alessandra, Salemi, Giuseppe, De Luca, Giovanna, Cottone, Salvatore, Conte, Antonella, Sola, Patrizia, Aguglia, Umberto, Maniscalco, Giorgia Teresa, Gasperini, Claudio, Ferrò, Maria Teresa, Pesci, Ilaria, Amato, Maria Pia, Rovaris, Marco, Solaro, Claudio, Lus, Giacomo, Maimone, Davide, Bergamaschi, Roberto, Granella, Franco, Di Sapio, Alessia, Bertolotto, Antonio, Totaro, Rocco, Vianello, Marika, Cavalla, Paola, Bellantonio, Paolo, Lepore, Vito, Patti, Francesco, and DIPARTIMENTO DI SCIENZE BIOMEDICHE E NEUROMOTORIE
Subjects: Adult, medicine.medical_specialty, Discontinuation rate, Neurology, Reasons for discontinuation, Population, Progressive Multifocal, Relapsing-Remitting, Settore MED/26, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, Leukoencephalopathy, Internal medicine, parasitic diseases, medicine, Effective treatment, Humans, Immunologic Factors, Multiple sclerosi, 030212 general & internal medicine, education, Retrospective Studies, education.field_of_study, Female, Middle Aged, Leukoencephalopathy, Progressive Multifocal, Multiple Sclerosis, business.industry, Progressive multifocal leukoencephalopathy, Retrospective cohort study, medicine.disease, Discontinuation, Settore MED/26 - Neurologia, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: none 38 no BACKGROUND: Natalizumab (NTZ) is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). However, patients and physicians may consider discontinuing NTZ therapy due to safety or efficacy issues. The aim of our study was to evaluate the NTZ discontinuation rate and reasons of discontinuation in a large Italian population of RRMS patients. MATERIALS AND METHODS: The data were extracted from the Italian MS registry in May 2018 and were collected from 51,845 patients in 69 Italian multiple sclerosis centers. MS patients with at least one NTZ infusion in the period between June 1st 2012 to May 15th 2018 were included. Discontinuation rates at each time point were calculated. Reasons for NTZ discontinuation were classified as "lack of efficacy", "progressive multifocal leukoencephalopathy (PML) risk" or "other". RESULTS: Out of 51,845, 5151 patients, 3019 (58.6%) females, with a mean age of 43.6 ± 10.1years (median 40), were analyzed. Out of 2037 (39.5%) who discontinued NTZ, a significantly higher percentage suspended NTZ because of PML risk compared to lack of efficacy [1682 (32.7% of 5151) vs 221 (4.3%), p
Published: 2021

24. SARS-CoV-2 serology after COVID-19 in multiple sclerosis: An international cohort study

Author: Maria Pia Sormani, Irene Schiavetti, Doriana Landi, Luca Carmisciano, Nicola De Rossi, Cinzia Cordioli, Lucia Moiola, Marta Radaelli, Paolo Immovilli, Marco Capobianco, Vincenzo Brescia Morra, Maria Trojano, Gioacchino Tedeschi, Giancarlo Comi, Mario Alberto Battaglia, Francesco Patti, Yara Dadalti Fragoso, Sedat Sen, Aksel Siva, Roberto Furlan, Marco Salvetti, Gianmarco Abbadessa, Umberto Aguglia, Lia Allegorico, Rossi Beatrice Maria Allegri, Maria Pia Amato, Pietro Annovazzi, Carlo Antozzi, Lucia Appendino, Sebastiano Arena, Viola Baione, Roberto Balgera, Valeria Barcella, Damiano Baroncini, Caterina Barrilà, Mario A. Battaglia, Alessandra Bellacosa, Gianmarco Bellucci, Roberto Bergamaschi, Valeria Bergamaschi, Daiana Bezzini, Beatrice Biolzi, Alvino Bisecco, Simona Bonavita, Giovanna Borriello, Chiara Bosa, Antonio Bosco, Francesca Bovis, Marco Bozzali, Laura Brambilla, Morra Vincenzo Brescia, Giampaolo Brichetto, Maria Buccafusca, Elisabetta Bucciantini, Sebastiano Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano Calabrese, Francesca Calabria, Francesca Caleri, Federico Camilli, Luisa Maria Caniatti, Roberto Cantello, Ruggero Capra, Rocco Capuano, Patrizia Carta, Paola Cavalla, Maria Grazia Celani, Maria Cellerino, Raffaella Cerqua, Clara Chisari, Raffaella Clerici, Marinella Clerico, Eleonora Cocco, Gaia Cola, Paolo Confalonieri, Antonella Conte, Marta Zaffira Conti, Christian Cordano, Susanna Cordera, Francesco Corea, Claudio Correale, Salvatore Cottone, Francesco Crescenzo, Erica Curti, Alessandro d’Ambrosio, Emanuele D’Amico, Maura Chiara Danni, Alessia d’Arma, Vincenzo Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Stefano, Marco Della Cava, Mario di Napoli, Alessia Di Sapio, Renato Docimo, Anna Dutto, Luana Evangelista, Salvatore Fanara, Diana Ferraro, Maria Teresa Ferrò, Massimo Filippi, Cristina Fioretti, Mario Fratta, Jessica Frau, Marzia Fronza, Alberto Gajofatto, Antonio Gallo, Paolo Gallo, Claudio Gasperini, Anna Ghazaryan, Bruno Giometto, Francesca Gobbin, Flora Govone, Franco Granella, Erica Grange, Maria Grazia Grasso, Angelica Guareschi, Clara Guaschino, Simone Guerrieri, Donata Guidetti, Pietro Iaffaldano, Antonio Ianniello, Luigi Iasevoli, Daniele Imperiale, Maria Teresa Infante, Matilde Inglese, Rosa Iodice, Aniello Iovino, Giovanna Konrad, Roberta Lanzillo, Caterina Lapucci, Luigi Lavorgna, Rita L’Episcopo Maria, Serena Leva, Giuseppe Liberatore, Marianna Lo Re, Marco Longoni, Leonardo Lopiano, Lorena Lorefice, Matteo Lucchini, Giacomo Lus, Davide Maimone, Maria Malentacchi, Giulia Mallucci, Simona Malucchi, Chiara Rosa Mancinelli, Luca Mancinelli, Paolo Manganotti, Teresa Giorgia Maniscalco, Vittorio Mantero, Sabrina Marangoni, Damiano Marastoni, Alessandra Girolama Marfia, Fabiana Marinelli, Alessandro Marti, Filippo Martinelli Boneschi, Federco Masserano Zoli, Francesca Matta, Laura Mendozzi, Giuseppe Meucci, Silvia Miante, Giuseppina Miele, Eva Milano, Massimiliano Mirabella, Rosanna Missione, Marcello Moccia, Sara Montepietra, Margherita Monti Bragadin, Federico Montini, Roberta Motta, Raffaele Nardone, Carolina Gabri Nicoletti, Eduardo Nobile-Orazio, Agostino Nozzolillo, Marco Onofrj, Riccardo Orlandi, Anna Palmieri, Damiano Paolicelli, Livia Pasquali, Luisa Pastò, Elisabetta Pedrazzoli, Paola Perini, Ilaria Pesci, Maria Petracca, Alfredo Petrone, Carlo Piantadosi, Anna M. Pietroboni, Federica Pinardi, Marta Ponzano, Emilio Portaccio, Mattia Pozzato, Carlo Pozzilli, Luca Prosperini, Alessandra Protti, Paolo Ragonese, Sarah Rasia, Sabrina Realmuto, Anna Repice, Eleonora Rigoni, Maria Teresa Rilla, Francesca Rinaldi, Calogero Marcello Romano, Marco Ronzoni, Marco Rovaris, Francesca Ruscica, Loredana Sabattini, Giuseppe Salemi, Lorenzo Saraceno, Alessia Sartori, Arianna Sartori, Elvira Sbragia, Cinzia Scandellari, Ilaria Scarano Giuditta, Valentina Scarano, Valentina Schillaci, Maria Sessa, Caterina Sgarito, Grazia Sibilia, Gabriele Siciliano, Alessio Signori, Elisabetta Signoriello, Leonardo Sinisi, Francesca Sireci, Patrizia Sola, Claudio Solaro, Stefano Sotgiu, Maddalena Sparaco, Maria Laura Stromillo, Silvia Strumia, Laura Emanuela Susani, Giulietta Tabiadon, Francesco Teatini, Valentina Tomassini, Simone Tonietti, Clerici Valentina Torri, Carla Tortorella, Simona Toscano, Rocco Totaro, Maria Trotta, Gabriella Turano, Monica Ulivelli, Manzo Valentino, Giovanna Vaula, Domizia Vecchio, Marco Vercellino, Elena Pinuccia Verrengia, Marika Vianello, Eleonora Virgilio, Francesca Vitetta, Stefano Vollaro, Mauro Zaffaroni, Mauro Zampolini, Ignazio Roberto Zarbo, Antonio Zito, Luigi Zuliani, Sormani, M. P., Schiavetti, I., Landi, D., Carmisciano, L., De Rossi, N., Cordioli, C., Moiola, L., Radaelli, M., Immovilli, P., Capobianco, M., Brescia Morra, V., Trojano, M., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Fragoso, Y. D., Sen, S., Siva, A., Furlan, R., Salvetti, M., Bisecco, Alvino, Pia Sormani, Maria, Schiavetti, Irene, Landi, Doriana, Carmisciano, Luca, De Rossi, Nicola, Cordioli, Cinzia, Moiola, Lucia, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, Brescia Morra, Vincenzo, Trojano, Maria, Tedeschi, Gioacchino, Comi, Giancarlo, Alberto Battaglia, Mario, Patti, Francesco, Dadalti Fragoso, Yara, Sen, Sedat, Siva, Aksel, Furlan, Roberto, Salvetti, Marco, Study Group Gianmarco Abbadessa, MuSC-19, Aguglia, Umberto, Allegorico, Lia, Beatrice Maria Allegri, Rossi, Pia Amato, Maria, Annovazzi, Pietro, Antozzi, Carlo, Appendino, Lucia, Arena, Sebastiano, Baione, Viola, Balgera, Roberto, Barcella, Valeria, Baroncini, Damiano, Barrilà, Caterina, A Battaglia, Mario, Bellacosa, Alessandra, Bellucci, Gianmarco, Bergamaschi, Roberto, Bergamaschi, Valeria, Bezzini, Daiana, Biolzi, Beatrice, Bonavita, Simona, Borriello, Giovanna, Bosa, Chiara, Bosco, Antonio, Bovis, Francesca, Bozzali, Marco, Brambilla, Laura, Vincenzo Brescia, Morra, Brichetto, Giampaolo, Buccafusca, Maria, Bucciantini, Elisabetta, Bucello, Sebastiano, Chiara Buscarinu, Maria, Paola Cabboi, Maria, Calabrese, Massimiliano, Calabria, Francesca, Caleri, Francesca, Camilli, Federico, Maria Caniatti, Luisa, Cantello, Roberto, Capra, Ruggero, Capuano, Rocco, Carta, Patrizia, Cavalla, Paola, Grazia Celani, Maria, Cellerino, Maria, Cerqua, Raffaella, Chisari, Clara, Clerici, Raffaella, Clerico, Marinella, Cocco, Eleonora, Cola, Gaia, Confalonieri, Paolo, Conte, Antonella, Zaffira Conti, Marta, Cordano, Christian, Cordera, Susanna, Corea, Francesco, Correale, Claudio, Cottone, Salvatore, Crescenzo, Francesco, Curti, Erica, D'Ambrosio, Alessandro, D'Amico, Emanuele, Chiara Danni, Maura, D'Arma, Alessia, Dattola, Vincenzo, de Biase, Stefano, De Luca, Giovanna, Federica De Mercanti, Stefania, De Mitri, Paolo, De Stefano, Nicola, Della Cava, Marco, di Napoli, Mario, Di Sapio, Alessia, Docimo, Renato, Dutto, Anna, Evangelista, Luana, Fanara, Salvatore, Ferraro, Diana, Teresa Ferrò, Maria, Filippi, Massimo, Fioretti, Cristina, Fratta, Mario, Frau, Jessica, Fronza, Marzia, Gajofatto, Alberto, Gallo, Antonio, Gallo, Paolo, Gasperini, Claudio, Ghazaryan, Anna, Giometto, Bruno, Gobbin, Francesca, Govone, Flora, Granella, Franco, Grange, Erica, Grazia Grasso, Maria, Guareschi, Angelica, Guaschino, Clara, Guerrieri, Simone, Guidetti, Donata, Iaffaldano, Pietro, Ianniello, Antonio, Iasevoli, Luigi, Imperiale, Daniele, Teresa Infante, Maria, Inglese, Matilde, Iodice, Rosa, Iovino, Aniello, Konrad, Giovanna, Lanzillo, Roberta, Lapucci, Caterina, Lavorgna, Luigi, L'Episcopo Maria, Rita, Leva, Serena, Liberatore, Giuseppe, Lo Re, Marianna, Longoni, Marco, Lopiano, Leonardo, Lorefice, Lorena, Lucchini, Matteo, Lus, Giacomo, Maimone, Davide, Malentacchi, Maria, Mallucci, Giulia, Malucchi, Simona, Rosa Mancinelli, Chiara, Mancinelli, Luca, Manganotti, Paolo, Giorgia Maniscalco, Teresa, Mantero, Vittorio, Marangoni, Sabrina, Marastoni, Damiano, Girolama Marfia, Alessandra, Marinelli, Fabiana, Marti, Alessandro, Martinelli Boneschi, Filippo, Masserano Zoli, Federco, Matta, Francesca, Mendozzi, Laura, Meucci, Giuseppe, Miante, Silvia, Miele, Giuseppina, Milano, Eva, Mirabella, Massimiliano, Missione, Rosanna, Moccia, Marcello, Montepietra, Sara, Monti Bragadin, Margherita, Montini, Federico, Motta, Roberta, Nardone, Raffaele, Gabri Nicoletti, Carolina, Nobile-Orazio, Eduardo, Nozzolillo, Agostino, Onofrj, Marco, Orlandi, Riccardo, Palmieri, Anna, Paolicelli, Damiano, Pasquali, Livia, Pastò, Luisa, Pedrazzoli, Elisabetta, Perini, Paola, Pesci, Ilaria, Petracca, Maria, Petrone, Alfredo, Piantadosi, Carlo, M Pietroboni, Anna, Pinardi, Federica, Ponzano, Marta, Portaccio, Emilio, Pozzato, Mattia, Pozzilli, Carlo, Prosperini, Luca, Protti, Alessandra, Ragonese, Paolo, Rasia, Sarah, Realmuto, Sabrina, Repice, Anna, Rigoni, Eleonora, Teresa Rilla, Maria, Rinaldi, Francesca, Marcello Romano, Calogero, Ronzoni, Marco, Rovaris, Marco, Ruscica, Francesca, Sabattini, Loredana, Salemi, Giuseppe, Saraceno, Lorenzo, Sartori, Alessia, Sartori, Arianna, Sbragia, Elvira, Scandellari, Cinzia, Scarano Giuditta, Ilaria, Scarano, Valentina, Schillaci, Valentina, Sessa, Maria, Sgarito, Caterina, Sibilia, Grazia, Siciliano, Gabriele, Signori, Alessio, Signoriello, Elisabetta, Sinisi, Leonardo, Sireci, Francesca, Sola, Patrizia, Solaro, Claudio, Sotgiu, Stefano, Sparaco, Maddalena, Laura Stromillo, Maria, Strumia, Silvia, Emanuela Susani, Laura, Tabiadon, Giulietta, Teatini, Francesco, Tomassini, Valentina, Tonietti, Simone, Valentina Torri, Clerici, Tortorella, Carla, Toscano, Simona, Totaro, Rocco, Trotta, Maria, Turano, Gabriella, Ulivelli, Monica, Valentino, Manzo, Vaula, Giovanna, Vecchio, Domizia, Vercellino, Marco, Pinuccia Verrengia, Elena, Vianello, Marika, Virgilio, Eleonora, Vitetta, Francesca, Vollaro, Stefano, Zaffaroni, Mauro, Zampolini, Mauro, Roberto Zarbo, Ignazio, Zito, Antonio, Zuliani, Luigi, Abbadessa, Gianmarco, Trotta, Maria Consiglia, and Zito, Guido Antonio
Subjects: 0301 basic medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), immunosuppressive therapie, coronavirus, Settore MED/26, medicine.disease_cause, Antibodies, Viral, immunosuppressive therapies, Antibodies, Serology, Cohort Studies, Multiple sclerosis, 03 medical and health sciences, 0302 clinical medicine, Seroepidemiologic Studies, Pandemic, Medicine, Humans, Multiple sclerosi, Viral, Coronavirus, business.industry, immunomodulatory therapie, immunomodulatory therapies, COVID-19, medicine.disease, Virology, coronaviru, Settore MED/26 - NEUROLOGIA, Sars-COV-2, 030104 developmental biology, Neurology, Neurology (clinical), business, SARS-CoV-2, Multiple Sclerosis, 030217 neurology & neurosurgery, Cohort study
Abstract: Background: The MuSC-19 project is an Italian cohort study open to international partners that collects data on multiple sclerosis (MS) patients with COVID-19. During the second wave of the pandemic, serological tests became routinely available. Objective: To evaluate the seroprevalence of anti-SARS-CoV-2 antibodies according to the use of disease-modifying therapy (DMT) in a subset of patients included in the MuSC-19 data set who had undergone a serological test. Methods: We evaluated the association between positive serological test results and time elapsed since infection onset, age, sex, Expanded Disability Status Scale score, comorbidities and DMT exposure using a multivariable logistic model. Results: Data were collected from 423 patients (345 from Italy, 61 from Turkey and 17 from Brazil) with a serological test performed during follow-up. Overall, 325 out of 423 tested patients (76.8%) had a positive serological test. At multivariate analysis, therapy with anti-CD20 was significantly associated with a reduced probability of developing antibodies after COVID-19 (odds ratio (OR) = 0.20, p = 0.002). Conclusion: Patients with MS maintain the capacity to develop humoral immune response against SARS-COV-2, although to a lesser extent when treated with anti-CD20 drugs. Overall, our results are reassuring with respect to the possibility to achieve sufficient immunization with vaccination.
Published: 2021

25. COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Author: Maria Pia Sormani, Irene Schiavetti, Luca Carmisciano, Cinzia Cordioli, Massimo Filippi, Marta Radaelli, Paolo Immovilli, Marco Capobianco, Nicola De Rossi, Giampaolo Brichetto, Eleonora Cocco, Cinzia Scandellari, Paola Cavalla, Ilaria Pesci, Antonio Zito, Paolo Confalonieri, Girolama Alessandra Marfia, Paola Perini, Matilde Inglese, Maria Trojano, Vincenzo Brescia Morra, Gioacchino Tedeschi, Giancarlo Comi, Mario Alberto Battaglia, Francesco Patti, Marco Salvetti, Gianmarco Abbadessa, Umberto Aguglia, Lia Allegorico, Beatrice Maria Allegri Rossi, Maria Pia Amato, Pietro Annovazzi, Carlo Antozzi, Lucia Appendino, Sebastiano Arena, Viola Baione, Roberto Balgera, Valeria Barcella, Damiano Baroncini, Caterina Barrilà, Alessandra Bellacosa, Gianmarco Bellucci, Roberto Bergamaschi, Valeria Bergamaschi, Daiana Bezzini, Beatrice Biolzi, Alvino Bisecco, Simona Bonavita, Giovanna Borriello, Chiara Bosa, Antonio Bosco, Francesca Bovis, Marco Bozzali, Laura Brambilla, Maria Buccafusca, Elisabetta Bucciantini, Sebastiano Bucello, Maria Chiara Buscarinu, Maria Paola Cabboi, Massimiliano Calabrese, Francesca Calabria, Francesca Caleri, Federico Camilli, Luisa Maria Caniatti, Roberto Cantello, Ruggero Capra, Rocco Capuano, Patrizia Carta, Maria Grazia Celani, Maria Cellerino, Raffaella Cerqua, Clara Chisari, Raffaella Clerici, Marinella Clerico, Gaia Cola, Antonella Conte, Marta Zaffira Conti, Christian Cordano, Susanna Cordera, Francesco Corea, Claudio Correale, Salvatore Cottone, Francesco Crescenzo, Erica Curti, Alessandro d'Ambrosio, Emanuele D'Amico, Maura Chiara Danni, Alessia d'Arma, Vincenzo Dattola, Stefano de Biase, Giovanna De Luca, Stefania Federica De Mercanti, Paolo De Mitri, Nicola De Stefano, Marco Della Cava, Mario di Napoli, Alessia Di Sapio, Renato Docimo, Anna Dutto, Luana Evangelista, Salvatore Fanara, Ferraro Diana, Maria Teresa Ferrò, Cristina Fioretti, Mario Fratta, Jessica Frau, Marzia Fronza, Roberto Furlan, Alberto Gajofatto, Antonio Gallo, Paolo Gallo, Claudio Gasperini, Anna Ghazaryan, Bruno Giometto, Francesca Gobbin, Flora Govone, Franco Granella, Erica Grange, Maria Grazia Grasso, Angelica Guareschi, Clara Guaschino, Simone Guerrieri, Donata Guidetti, Pietro Iaffaldano, Antonio Ianniello, Luigi Iasevoli, Daniele Imperiale, Maria Teresa Infante, Rosa Iodice, Aniello Iovino, Giovanna Konrad, Doriana Landi, Roberta Lanzillo, Caterina Lapucci, Luigi Lavorgna, Maria Rita L'Episcopo, Serena Leva, Giuseppe Liberatore, Marianna Lo Re, Marco Longoni, Leonardo Lopiano, Lorena Lorefice, Matteo Lucchini, Giacomo Lus, Davide Maimone, Maria Malentacchi, Giulia Mallucci, Simona Malucchi, Chiara Rosa Mancinelli, Luca Mancinelli, Paolo Manganotti, Giorgia Teresa Maniscalco, Vittorio Mantero, Sabrina Marangoni, Damiano Marastoni, Fabiana Marinelli, Alessandro Marti, Filippo Martinelli Boneschi, Federco Masserano Zoli, Francesca Matta, Laura Mendozzi, Giuseppe Meucci, Silvia Miante, Giuseppina Miele, Eva Milano, Massimiliano Mirabella, Rosanna Missione, Marcello Moccia, Lucia Moiola, Sara Montepietra, Margherita MontiBragadin, Federico Montini, Roberta Motta, Raffaele Nardone, Carolina Gabri Nicoletti, Eduardo Nobile-Orazio, Agostino Nozzolillo, Marco Onofrj, Riccardo Orlandi, Anna Palmieri, Damiano Paolicelli, Livia Pasquali, Luisa Pastò, Elisabetta Pedrazzoli, Maria Petracca, Alfredo Petrone, Carlo Piantadosi, Anna M Pietroboni, Federica Pinardi, Marta Ponzano, Emilio Portaccio, Mattia Pozzato, Carlo Pozzilli, Luca Prosperini, Alessandra Protti, Paolo Ragonese, Sarah Rasia, Sabrina Realmuto, Anna Repice, Eleonora Rigoni, Maria Teresa Rilla, Francesca Rinaldi, Calogero Marcello Romano, Marco Ronzoni, Marco Rovaris, Francesca Ruscica, Loredana Sabattini, Giuseppe Salemi, Lorenzo Saraceno, Alessia Sartori, Arianna Sartori, Elvira Sbragia, Giuditta Ilaria Scarano, Valentina Scarano, Valentina Schillaci, Maria Sessa, Caterina Sgarito, Grazia Sibilia, Gabriele Siciliano, Alessio Signori, Elisabetta Signoriello, Leonardo Sinisi, Francesca Sireci, Patrizia Sola, Claudio Solaro, Stefano Sotgiu, Maddalena Sparaco, Maria Laura Stromillo, Silvia Strumia, Emanuela Laura Susani, Giulietta Tabiadon, Francesco Teatini, Valentina Tomassini, Simone Tonietti, Clerici Valentina Torri, Carla Tortorella, Simona Toscano, Rocco Totaro, Maria Trotta, Gabriella Turano, Monica Ulivelli, Manzo Valentino, Giovanna Vaula, Domizia Vecchio, Marco Vercellino, Elena Pinuccia Verrengia, Marika Vianello, Eleonora Virgilio, Francesca Vitetta, Stefano Vollaro, Mauro Zaffaroni, Mauro Zampolini, Ignazio Roberto Zarbo, Luigi Zuliani, Pia Sormani, Maria, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Filippi, Massimo, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, De Rossi, Nicola, Brichetto, Giampaolo, Cocco, Eleonora, Scandellari, Cinzia, Cavalla, Paola, Pesci, Ilaria, Zito, Guido Antonio, Confalonieri, Paolo, Alessandra Marfia, Girolama, Perini, Paola, Inglese, Matilde, Trojano, Maria, Brescia Morra, Vincenzo, Tedeschi, Gioacchino, Comi, Giancarlo, Alberto Battaglia, Mario, Patti, Francesco, Salvetti, Marco, Abbadessa, Gianmarco, Aguglia, Umberto, Allegorico, Lia, Maria Allegri Rossi, Beatrice, Pia Amato, Maria, Annovazzi, Pietro, Antozzi, Carlo, Appendino, Lucia, Arena, Sebastiano, Baione, Viola, Balgera, Roberto, Barcella, Valeria, Baroncini, Damiano, Barrilà, Caterina, Bellacosa, Alessandra, Bellucci, Gianmarco, Bergamaschi, Roberto, Bergamaschi, Valeria, Bezzini, Daiana, Biolzi, Beatrice, Bisecco, Alvino, Bonavita, Simona, Borriello, Giovanna, Bosa, Chiara, Bosco, Antonio, Bovis, Francesca, Bozzali, Marco, Brambilla, Laura, Buccafusca, Maria, Bucciantini, Elisabetta, Bucello, Sebastiano, Chiara Buscarinu, Maria, Paola Cabboi, Maria, Calabrese, Massimiliano, Calabria, Francesca, Caleri, Francesca, Camilli, Federico, Maria Caniatti, Luisa, Cantello, Roberto, Capra, Ruggero, Capuano, Rocco, Carta, Patrizia, Grazia Celani, Maria, Cellerino, Maria, Cerqua, Raffaella, Chisari, Clara, Clerici, Raffaella, Clerico, Marinella, Cola, Gaia, Conte, Antonella, Zaffira Conti, Marta, Cordano, Christian, Cordera, Susanna, Corea, Francesco, Correale, Claudio, Cottone, Salvatore, Crescenzo, Francesco, Curti, Erica, D'Ambrosio, Alessandro, D'Amico, Emanuele, Chiara Danni, Maura, D'Arma, Alessia, Dattola, Vincenzo, de Biase, Stefano, De Luca, Giovanna, Federica De Mercanti, Stefania, De Mitri, Paolo, De Stefano, Nicola, Della Cava, Marco, di Napoli, Mario, Di Sapio, Alessia, Docimo, Renato, Dutto, Anna, Evangelista, Luana, Fanara, Salvatore, Diana, Ferraro, Teresa Ferrò, Maria, Fioretti, Cristina, Fratta, Mario, Frau, Jessica, Fronza, Marzia, Furlan, Roberto, Gajofatto, Alberto, Gallo, Antonio, Gallo, Paolo, Gasperini, Claudio, Ghazaryan, Anna, Giometto, Bruno, Gobbin, Francesca, Govone, Flora, Granella, Franco, Grange, Erica, Grazia Grasso, Maria, Guareschi, Angelica, Guaschino, Clara, Guerrieri, Simone, Guidetti, Donata, Iaffaldano, Pietro, Ianniello, Antonio, Iasevoli, Luigi, Imperiale, Daniele, Teresa Infante, Maria, Iodice, Rosa, Iovino, Aniello, Konrad, Giovanna, Landi, Doriana, Lanzillo, Roberta, Lapucci, Caterina, Lavorgna, Luigi, Rita L'Episcopo, Maria, Leva, Serena, Liberatore, Giuseppe, Lo Re, Marianna, Longoni, Marco, Lopiano, Leonardo, Lorefice, Lorena, Lucchini, Matteo, Lus, Giacomo, Maimone, Davide, Malentacchi, Maria, Mallucci, Giulia, Malucchi, Simona, Rosa Mancinelli, Chiara, Mancinelli, Luca, Manganotti, Paolo, Teresa Maniscalco, Giorgia, Mantero, Vittorio, Marangoni, Sabrina, Marastoni, Damiano, Marinelli, Fabiana, Marti, Alessandro, Martinelli Boneschi, Filippo, Masserano Zoli, Federco, Matta, Francesca, Mendozzi, Laura, Meucci, Giuseppe, Miante, Silvia, Miele, Giuseppina, Milano, Eva, Mirabella, Massimiliano, Missione, Rosanna, Moccia, Marcello, Moiola, Lucia, Montepietra, Sara, Montibragadin, Margherita, Montini, Federico, Motta, Roberta, Nardone, Raffaele, Gabri Nicoletti, Carolina, Nobile-Orazio, Eduardo, Nozzolillo, Agostino, Onofrj, Marco, Orlandi, Riccardo, Palmieri, Anna, Paolicelli, Damiano, Pasquali, Livia, Pastò, Luisa, Pedrazzoli, Elisabetta, Petracca, Maria, Petrone, Alfredo, Piantadosi, Carlo, M Pietroboni, Anna, Pinardi, Federica, Ponzano, Marta, Portaccio, Emilio, Pozzato, Mattia, Pozzilli, Carlo, Prosperini, Luca, Protti, Alessandra, Ragonese, Paolo, Rasia, Sarah, Realmuto, Sabrina, Repice, Anna, Rigoni, Eleonora, Teresa Rilla, Maria, Rinaldi, Francesca, Marcello Romano, Calogero, Ronzoni, Marco, Rovaris, Marco, Ruscica, Francesca, Sabattini, Loredana, Salemi, Giuseppe, Saraceno, Lorenzo, Sartori, Alessia, Sartori, Arianna, Sbragia, Elvira, Ilaria Scarano, Giuditta, Scarano, Valentina, Schillaci, Valentina, Sessa, Maria, Sgarito, Caterina, Sibilia, Grazia, Siciliano, Gabriele, Signori, Alessio, Signoriello, Elisabetta, Sinisi, Leonardo, Sireci, Francesca, Sola, Patrizia, Solaro, Claudio, Sotgiu, Stefano, Sparaco, Maddalena, Laura Stromillo, Maria, Strumia, Silvia, Laura Susani, Emanuela, Tabiadon, Giulietta, Teatini, Francesco, Tomassini, Valentina, Tonietti, Simone, Valentina Torri, Clerici, Tortorella, Carla, Toscano, Simona, Totaro, Rocco, Trotta, Maria Consiglia, Turano, Gabriella, Ulivelli, Monica, Valentino, Manzo, Vaula, Giovanna, Vecchio, Domizia, Vercellino, Marco, Pinuccia Verrengia, Elena, Vianello, Marika, Virgilio, Eleonora, Vitetta, Francesca, Vollaro, Stefano, Zaffaroni, Mauro, Zampolini, Mauro, Roberto Zarbo, Ignazio, Zuliani, Luigi, Sormani, M. P., Schiavetti, I., Carmisciano, L., Cordioli, C., Filippi, M., Radaelli, M., Immovilli, P., Capobianco, M., De Rossi, N., Brichetto, G., Cocco, E., Scandellari, C., Cavalla, P., Pesci, I., Zito, A., Confalonieri, P., Marfia, G. A., Perini, P., Inglese, M., Trojano, M., Brescia Morra, V., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., Zito, Antonio, BRESCIA MORRA, Vincenzo, Trotta, Maria, Sormani, Maria Pia, Marfia, Girolama Alessandra, and Battaglia, Mario Alberto
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Coronavirus disease 2019 (COVID-19), Population, Intensive Care Unit, COVID-19, Cohort Studies, Comorbidity, Female, Hospitalization, Humans, Intensive Care Units, Italy, Middle Aged, Retrospective Studies, Risk Factors, Severity of Illness Index, Context (language use), Settore MED/26, Lower risk, Retrospective Studie, Internal medicine, Multiple Sclerosi, Medicine, In patient, National level, education, education.field_of_study, Expanded Disability Status Scale, business.industry, Risk Factor, Ethics committee, medicine.disease, Icu admission, Settore MED/26 - NEUROLOGIA, Neurology, Relative risk, Family medicine, Cohort, Honorarium, Observational study, Neurology (clinical), Cohort Studie, business, Human
Abstract: Background: It is unclear how multiple sclerosis (MS) affects the severity of Covid-19. Methods: Hospitalization, Intensive Care Unit (ICU) admission and death after Covid-19 diagnosis of 1362 MS patients were compared to the age and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher-risk: EDSS>3 or at least one comorbidity, lower-risk: EDSS
Published: 2021

26. Exit Strategies in Natalizumab-Treated RRMS at High Risk of Progressive Multifocal Leukoencephalopathy: a Multicentre Comparison Study

Author: Gianmarco Abbadessa, Carlo Avolio, Patrizia Sola, Franco Granella, Graziella Callari, Stefania Barone, Elisabetta Signoriello, Simona Bonavita, Francesco Patti, Aurora Zanghì, Maria Buccafusca, Valeria Di Francescantonio, Antonio Gallo, Rocco Capuano, Diana Ferraro, Roberta Lanzillo, Paola Valentino, Matteo Lucchini, Erica Curti, Giuseppe Pontillo, Massimiliano Mirabella, Emanuele D'Amico, Maria Petracca, Giacomo Lus, Zanghì, Aurora, Gallo, Antonio, Avolio, Carlo, Capuano, Rocco, Lucchini, Matteo, Petracca, Maria, Bonavita, Simona, Lanzillo, Roberta, Ferraro, Diana, Curti, Erica, Buccafusca, Maria, Callari, Graziella, Barone, Stefania, Pontillo, Giuseppe, Abbadessa, Gianmarco, Di Francescantonio, Valeria, Signoriello, Elisabetta, Lus, Giacomo, Sola, Patrizia, Granella, Franco, Valentino, Paola, Mirabella, Massimiliano, Patti, Francesco, D'Amico, Emanuele, Zanghi, A., Gallo, A., Avolio, C., Capuano, R., Lucchini, M., Petracca, M., Bonavita, S., Lanzillo, R., Ferraro, D., Curti, E., Buccafusca, M., Callari, G., Barone, S., Pontillo, G., Abbadessa, G., Di Francescantonio, V., Signoriello, E., Lus, G., Sola, P., Granella, F., Valentino, P., Mirabella, M., Patti, F., and D'Amico, E.
Subjects: 0301 basic medicine, Male, Immunosuppressive Agent, 0302 clinical medicine, Natalizumab, Immunologic Factor, Risk Factors, Retrospective Studie, Pharmacology (medical), Prospective Studies, Disease activity, Ocrelizumab, Drug Substitution, Progressive multifocal leukoencephalopathy, Leukoencephalopathy, Progressive Multifocal, Settore MED/26 - NEUROLOGIA, Original Article, Rituximab, Female, Immunosuppressive Agents, medicine.drug, Human, Adult, medicine.medical_specialty, Adolescent, Lower risk, Antibodies, Monoclonal, Humanized, Cladribine, Exit strategy, Follow-Up Studie, 03 medical and health sciences, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Post-hoc analysis, medicine, Humans, Immunologic Factors, Retrospective Studies, Pharmacology, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Risk Factor, medicine.disease, Prospective Studie, 030104 developmental biology, Neurology (clinical), business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: The main aim of the study is to evaluate the efficacy and safety profile of ocrelizumab (OCR), rituximab (RTX), and cladribine (CLA), employed as natalizumab (NTZ) exit strategies in relapsing–remitting multiple sclerosis (RRMS) patients at high-risk for progressive multifocal leukoencephalopathy (PML). This is a multicentre, retrospective, real-world study on consecutive RRMS patients from eleven tertiary Italian MS centres, who switched from NTZ to OCR, RTX, and CLA from January 1st, 2019, to December 31st, 2019. The primary study outcomes were the annualized relapse rate (ARR) and magnetic resonance imaging (MRI) outcome. Treatment effects were estimated by the inverse probability treatment weighting (IPTW), based on propensity-score (PS) approach. Additional endpoint included confirmed disability progression (CDP) as measured by Expanded Disability Status Scale and adverse events (AEs). Patients satisfying predefined inclusion and exclusion criteria were 120; 64 switched to OCR, 36 to RTX, and 20 to CLA. Patients from the 3 groups did not show differences for baseline characteristics, also after post hoc analysis. The IPTW PS-adjusted models revealed that patients on OCR had a lower risk for ARR than patients on CLA (ExpBOCR0.485, CI 95% 0.264–0.893,p = 0.020). This result was confirmed also for 12-month MRI activity (ExpBOCR0.248 CI 95% 0.065–0.948,p = 0.042). No differences were found in other pairwise comparisons (OCR vs RTX and RTX vs CLA) for the investigated outcomes. AEs were similar among the 3 groups. Anti-CD20 drugs were revealed to be effective and safe options as NTZ exit strategies. All investigated DMTs showed a good safety profile.
Published: 2021

27. Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Author: Sormani, Maria P., Nicola De Rossi, Irene, Schiavetti, Luca, Carmisciano, Cinzia, Cordioli, Lucia, Moiola, Marta, Radaelli, Paolo, Immovilli, Marco, Capobianco, Maria, Trojano, Paola, Zaratin, Gioacchino, Tedeschi, Giancarlo, Comi, Battaglia, Mario A., Francesco, Patti, Marco, Salvetti, Agostino, Nozzolillo, Alessandra, Bellacosa, Alessandra, Protti, Alessia Di Sapio, Alessio, Signori, Alfredo, Petrone, Alvino, Bisecco, Aniello, Iovino, Anna, Dutto, Anna Maria Repice, Antonella, Conte, Antonio, Bertolotto, Antonio, Bosco, Antonio, Gallo, Antonio, Zito, Arianna, Sartori, Bruno, Giometto, Carla, Tortorella, Carlo, Antozzi, Carlo, Pozzilli, Chiara Rosa Mancinelli, Chiara, Zanetta, Christian, Cordano, Cinzia, Scandellari, Clara, Guaschino, Claudio, Gasperini, Claudio, Solaro, Cristina, Fioretti, Daiana, Bezzini, Damiano, Marastoni, Damiano, Paolicelli, Domizia, Vecchio, Doriana, Landi, Elisabetta, Bucciantini, Elisabetta, Pedrazzoli, Elisabetta, Signoriello, Elvira, Sbragia, Emanuela Laura Susani, Erica, Curti, Eva, Milano, Fabiana, Marinelli, Federico, Camilli, Filippo Martinelli Boneschi, Flora, Govone, Francesca, Bovis, Francesca, Calabria, Francesca, Caleri, Francesca, Rinaldi, Francesca, Vitetta, Francesco, Corea, Francesco, Crescenzo, Francesco, Teatini, Giulietta, Tabiadon, Franco, Granella, Giacomo, Boffa, Giacomo, Lus, Giampaolo, Brichetto, Giorgia Teresa Maniscalco, Giovanna, Borriello, Giovanna De Luca, Giovanna, Konrad, Giovanna, Vaula, Girolama Alessandra Marfia, Giulia, Mallucci, Giuseppe, Liberatore, Giuseppe, Salemi, Giuseppina, Miele, Grazia, Sibilia, Ilaria, Pesci, Laura, Brambilla, Leonardo, Lopiano, Leonardo, Sinisi, Pasquali, Livia, Lorenzo, Saraceno, Luca, Chiveri, Luca, Mancinelli, Grimaldi, Luigi M. E., Luisa Maria Caniatti, Marco Della Cava, Marco, Onofrj, Marco, Rovaris, Marco, Vercellino, Margherita Monti Bragadin, Maria, Buccafusca, Maria Chiara Buscarinu, Maria Grazia Celani, Maria Grazia Grasso, Maria Laura Stromillo, Maria, Petracca, Maria Pia Amato, Maria Pia Sormani, Maria Rita L'Episcopo, Maria, Sessa, Maria Teresa Ferrò, Maria Vittoria Ercolani, Mariangela, Bianco, Marianna Lo Re, Marika, Vianello, Marinella, Clerico, Mario Alberto Battaglia, Mario di Napoli, Marta, Ponzano, Marta Zaffira Conti, Massimiliano, Calabrese, Massimiliano, Mirabella, Massimo, Filippi, Matilde, Inglese, Matteo, Lucchini, Matteo, Pozzato, Maura Chiara Danni, Mauro, Zaffaroni, Mauro, Zampolini, Michela, Ponzio, Milena De Riz, Nicola De Stefano, Paola, Cavalla, Paola De Mitri, Paola, Grossi, Paolo, Confalonieri, Paolo, Gallo, Paolo, Ragonese, Patrizia, Sola, Pietro, Annovazzi, Pietro, Iaffaldano, Raffaele, Nardone, Raffaella, Cerqua, Raffaella, Clerici, Roberta, Lanzillo, Roberta, Motta, Roberto, Balgera, Roberto, Bergamaschi, Rocco, Totaro, Rosa, Iodice, Ruggero, Capra, Sabrina, Marangoni, Sabrina, Realmuto, Salvatore, Cottone, Sara, Montepietra, Sarah, Rasia, Sebastiano, Arena, Sebastiano, Bucello, Silvia, Banfi, Simona, Bonavita, Simona, Malucchi, Simone, Tonietti, Stefano, Vollaro, Susanna, Cordera, Umberto, Aguglia, Valentina Torri Clerici, Valeria, Barcella, Valeria, Bergamaschi, Vincenzo Brescia Morra, Vincenzo, Dattola, and Vittorio Mantero, Sormani, M. P., De Rossi, N., Schiavetti, I., Carmisciano, L., Cordioli, C., Moiola, L., Radaelli, M., Immovilli, P., Capobianco, M., Trojano, M., Zaratin, P., Tedeschi, G., Comi, G., Battaglia, M. A., Patti, F., Salvetti, M., P Sormani, Maria, De Rossi, Nicola, Schiavetti, Irene, Carmisciano, Luca, Cordioli, Cinzia, Moiola, Lucia, Radaelli, Marta, Immovilli, Paolo, Capobianco, Marco, Trojano, Maria, Zaratin, Paola, Tedeschi, Gioacchino, Comi, Giancarlo, A Battaglia, Mario, Patti, Francesco, Salvetti, Marco, Nozzolillo, Agostino, Bellacosa, Alessandra, Protti, Alessandra, Di Sapio, Alessia, Signori, Alessio, Petrone, Alfredo, Bisecco, Alvino, Iovino, Aniello, Dutto, Anna, Maria Repice, Anna, Conte, Antonella, Bertolotto, Antonio, Bosco, Antonio, Gallo, Antonio, Zito, Antonio, Sartori, Arianna, Giometto, Bruno, Tortorella, Carla, Antozzi, Carlo, Pozzilli, Carlo, Rosa Mancinelli, Chiara, Zanetta, Chiara, Cordano, Christian, Scandellari, Cinzia, Guaschino, Clara, Gasperini, Claudio, Solaro, Claudio, Fioretti, Cristina, Bezzini, Daiana, Marastoni, Damiano, Paolicelli, Damiano, Vecchio, Domizia, Landi, Doriana, Bucciantini, Elisabetta, Pedrazzoli, Elisabetta, Signoriello, Elisabetta, Sbragia, Elvira, Laura Susani, Emanuela, Curti, Erica, Milano, Eva, Marinelli, Fabiana, Camilli, Federico, Martinelli Boneschi, Filippo, Govone, Flora, Bovis, Francesca, Calabria, Francesca, Caleri, Francesca, Rinaldi, Francesca, Vitetta, Francesca, Corea, Francesco, Crescenzo, Francesco, Teatini, Francesco, Tabiadon, Giulietta, Granella, Franco, Boffa, Giacomo, Lus, Giacomo, Brichetto, Giampaolo, Teresa Maniscalco, Giorgia, Borriello, Giovanna, De Luca, Giovanna, Konrad, Giovanna, Vaula, Giovanna, Alessandra Marfia, Girolama, Mallucci, Giulia, Liberatore, Giuseppe, Salemi, Giuseppe, Miele, Giuseppina, Sibilia, Grazia, Pesci, Ilaria, Brambilla, Laura, Lopiano, Leonardo, Sinisi, Leonardo, Pasquali, Livia, Saraceno, Lorenzo, Chiveri, Luca, Mancinelli, Luca, E Grimaldi, Luigi M, Maria Caniatti, Luisa, Della Cava, Marco, Onofrj, Marco, Rovaris, Marco, Vercellino, Marco, Monti Bragadin, Margherita, Buccafusca, Maria, Chiara Buscarinu, Maria, Grazia Celani, Maria, Grazia Grasso, Maria, Laura Stromillo, Maria, Petracca, Maria, Pia Amato, Maria, Pia Sormani, Maria, Rita L'Episcopo, Maria, Sessa, Maria, Teresa Ferrò, Maria, Vittoria Ercolani, Maria, Bianco, Mariangela, Lo Re, Marianna, Vianello, Marika, Clerico, Marinella, Alberto Battaglia, Mario, di Napoli, Mario, Ponzano, Marta, Zaffira Conti, Marta, Calabrese, Massimiliano, Mirabella, Massimiliano, Filippi, Massimo, Inglese, Matilde, Lucchini, Matteo, Pozzato, Matteo, Chiara Danni, Maura, Zaffaroni, Mauro, Zampolini, Mauro, Ponzio, Michela, De Riz, Milena, De Stefano, Nicola, Cavalla, Paola, De Mitri, Paola, Grossi, Paola, Confalonieri, Paolo, Gallo, Paolo, Ragonese, Paolo, Sola, Patrizia, Annovazzi, Pietro, Iaffaldano, Pietro, Nardone, Raffaele, Cerqua, Raffaella, Clerici, Raffaella, Lanzillo, Roberta, Motta, Roberta, Balgera, Roberto, Bergamaschi, Roberto, Totaro, Rocco, Iodice, Rosa, Capra, Ruggero, Marangoni, Sabrina, Realmuto, Sabrina, Cottone, Salvatore, Montepietra, Sara, Rasia, Sarah, Arena, Sebastiano, Bucello, Sebastiano, Banfi, Silvia, Bonavita, Simona, Malucchi, Simona, Tonietti, Simone, Vollaro, Stefano, Cordera, Susanna, Aguglia, Umberto, Torri Clerici, Valentina, Barcella, Valeria, Bergamaschi, Valeria, Brescia Morra, Vincenzo, Dattola, Vincenzo, Mantero, Vittorio, Mp, Sormani, N, De Rossi, I, Schiavetti, L, Carmisciano, C, Cordioli, L, Moiola, M, Radaelli, P, Immovilli, M, Capobianco, M, Trojano, P, Zaratin, G, Tedeschi, G, Comi, Ma, Battaglia, F, Patti, M, Salvetti, Study Group Agostino Nozzolillo, Musc-19, Grimaldi, Luigi M. E., Vittorio Mantero, And, Nozzolillo, A., Bellacosa, A., Protti, A., Di Sapio, A., Signori, A., Petrone, A., Bisecco, A., Iovino, A., Dutto, A., Repice, A. M., Conte, A., Bertolotto, A., Bosco, A., Gallo, A., Zito, A., Sartori, A., Giometto, B., Tortorella, C., Antozzi, C., Pozzilli, C., Mancinelli, C. R., Zanetta, C., Cordano, C., Scandellari, C., Guaschino, C., Gasperini, C., Solaro, C., Fioretti, C., Bezzini, D., Marastoni, D., Paolicelli, D., Vecchio, D., Landi, D., Bucciantini, E., Pedrazzoli, E., Signoriello, E., Sbragia, E., Susani, E. L., Curti, E., Milano, E., Marinelli, F., Camilli, F., Boneschi, F. M., Govone, F., Bovis, F., Calabria, F., Caleri, F., Rinaldi, F., Vitetta, F., Corea, F., Crescenzo, F., Teatini, F., Tabiadon, G., Granella, F., Boffa, G., Lus, G., Brichetto, G., Maniscalco, G. T., Borriello, G., De Luca, G., Konrad, G., Vaula, G., Marfia, G. A., Mallucci, G., Liberatore, G., Salemi, G., Miele, G., Sibilia, G., Pesci, I., Brambilla, L., Lopiano, L., Sinisi, L., Pasquali, L., Saraceno, L., Chiveri, L., Mancinelli, L., Grimaldi, L. M. E., Caniatti, L. M., Cava, M. D., Onofrj, M., Rovaris, M., Vercellino, M., Bragadin, M. M., Buccafusca, M., Buscarinu, M. C., Celani, M. G., Grasso, M. G., Stromillo, M. L., Petracca, M., Amato, M. P., L'Episcopo, M. R., Sessa, M., Ferro, M. T., Ercolani, M. V., Bianco, M., Re, M. L., Vianello, M., Clerico, M., di Napoli, M., Ponzano, M., Conti, M. Z., Calabrese, M., Mirabella, M., Filippi, M., Inglese, M., Lucchini, M., Pozzato, M., Danni, M. C., Zaffaroni, M., Zampolini, M., Ponzio, M., De Riz, M., De Stefano, N., Cavalla, P., De Mitri, P., Grossi, P., Confalonieri, P., Gallo, P., Ragonese, P., Sola, P., Annovazzi, P., Iaffaldano, P., Nardone, R., Cerqua, R., Clerici, R., Lanzillo, R., Motta, R., Balgera, R., Bergamaschi, R., Totaro, R., Iodice, R., Capra, R., Marangoni, S., Realmuto, S., Cottone, S., Montepietra, S., Rasia, S., Arena, S., Bucello, S., Banfi, S., Bonavita, S., Malucchi, S., Tonietti, S., Vollaro, S., Cordera, S., Aguglia, U., Clerici, V. T., Barcella, V., Bergamaschi, V., Morra, V. B., Dattola, V., Mantero, V., Sormani M.P., De Rossi N., Schiavetti I., Carmisciano L., Cordioli C., Moiola L., Radaelli M., Immovilli P., Capobianco M., Trojano M., Zaratin P., Tedeschi G., Comi G., Battaglia M.A., Patti F., Salvetti M., Nozzolillo A., Bellacosa A., Protti A., Di Sapio A., Signori A., Petrone A., Bisecco A., Iovino A., Dutto A., Repice A.M., Conte A., Bertolotto A., Bosco A., Gallo A., Zito A., Sartori A., Giometto B., Tortorella C., Antozzi C., Pozzilli C., Mancinelli C.R., Zanetta C., Cordano C., Scandellari C., Guaschino C., Gasperini C., Solaro C., Fioretti C., Bezzini D., Marastoni D., Paolicelli D., Vecchio D., Landi D., Bucciantini E., Pedrazzoli E., Signoriello E., Sbragia E., Susani E.L., Curti E., Milano E., Marinelli F., Camilli F., Boneschi F.M., Govone F., Bovis F., Calabria F., Caleri F., Rinaldi F., Vitetta F., Corea F., Crescenzo F., Teatini F., Tabiadon G., Granella F., Boffa G., Lus G., Brichetto G., Maniscalco G.T., Borriello G., De Luca G., Konrad G., Vaula G., Marfia G.A., Mallucci G., Liberatore G., Salemi G., Miele G., Sibilia G., Pesci I., Brambilla L., Lopiano L., Sinisi L., Pasquali L., Saraceno L., Chiveri L., Mancinelli L., Grimaldi L.M.E., Caniatti L.M., Cava M.D., Onofrj M., Rovaris M., Vercellino M., Bragadin M.M., Buccafusca M., Buscarinu M.C., Celani M.G., Grasso M.G., Stromillo M.L., Petracca M., Amato M.P., L'Episcopo M.R., Sessa M., Ferro M.T., Ercolani M.V., Bianco M., Re M.L., Vianello M., Clerico M., di Napoli M., Ponzano M., Conti M.Z., Calabrese M., Mirabella M., Filippi M., Inglese M., Lucchini M., Pozzato M., Danni M.C., Zaffaroni M., Zampolini M., Ponzio M., De Riz M., De Stefano N., Cavalla P., De Mitri P., Grossi P., Confalonieri P., Gallo P., Ragonese P., Sola P., Annovazzi P., Iaffaldano P., Nardone R., Cerqua R., Clerici R., Lanzillo R., Motta R., Balgera R., Bergamaschi R., Totaro R., Iodice R., Capra R., Marangoni S., Realmuto S., Cottone S., Montepietra S., Rasia S., Arena S., Bucello S., Banfi S., Bonavita S., Malucchi S., Tonietti S., Vollaro S., Cordera S., Aguglia U., Clerici V.T., Barcella V., Bergamaschi V., Morra V.B., Dattola V., and Mantero V.
Subjects: Male, 0301 basic medicine, Dimethyl Fumarate, Neurodegenerative, multiple sclerosis, coronavirus, pneumonia, Severity of Illness Index, law.invention, Immunosuppressive Agent, Immunologic Factor, 0302 clinical medicine, Natalizumab, law, Monoclonal, Multiple Sclerosi, 80 and over, Lung, Humanized, Research Articles, Aged, 80 and over, Middle Aged, Intensive care unit, Hospitalization, Settore MED/26 - NEUROLOGIA, Intensive Care Units, Neurology, Methylprednisolone, Neurological, Pneumonia & Influenza, Interferon, Female, Immunosuppressive Agents, Research Article, Human, medicine.drug, Adult, medicine.medical_specialty, Musc-19 Study Group, Multiple Sclerosis, Adolescent, Clinical Sciences, Intensive Care Unit, Clinical Neurology, Settore MED/26, Antibodies, Monoclonal, Humanized, Autoimmune Disease, Antibodies, Young Adult, 03 medical and health sciences, Clinical Research, Internal medicine, Severity of illness, medicine, Humans, Immunologic Factors, Mortality, Aged, COVID-19, Fingolimod Hydrochloride, Interferons, SARS-CoV-2, Neurology & Neurosurgery, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Neurosciences, Pneumonia, Odds ratio, medicine.disease, Brain Disorders, Good Health and Well Being, 030104 developmental biology, Ocrelizumab, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18–4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (
Published: 2021

28. Disease-modifying drugs can reduce disability progression in relapsing multiple sclerosis

Author: Rocco Totaro, Umberto Aguglia, Pietro Iaffaldano, Ciro Florio, Giuseppe Salemi, Giacomo Lus, Giovanna De Luca, Maurizia Gatto, Emilio Portaccio, Francesco Ottavio Logullo, Marta Simone, Angelo Ghezzi, Eleonora Cocco, Carlo Pozzilli, Simonetta Galgani, Matilde Inglese, Francesco Patti, Enrico Millefiorini, Giuseppe Lucisano, Giancarlo Di Battista, Roberto Bergamaschi, Maria Trojano, Franco Granella, Maria Pia Amato, Patrizia Sola, M. Vianello, Laura Tudisco, Roberto Fratangelo, Lorenzo Razzolini, Giancarlo Comi, Mattia Fonderico, Elio Prestipino, Angelo Bellinvia, Luisa Pastò, Mauro Zaffaroni, Marco Salvetti, Vincenzo Brescia Morra, Amato, Maria Pia, Fonderico, Mattia, Portaccio, Emilio, Pastò, Luisa, Razzolini, Lorenzo, Prestipino, Elio, Bellinvia, Angelo, Tudisco, Laura, Fratangelo, Roberto, Comi, Giancarlo, Patti, Francesco, De Luca, Giovanna, Brescia Morra, Vincenzo, Cocco, Eleonora, Pozzilli, Carlo, Sola, Patrizia, Bergamaschi, Roberto, Salemi, Giuseppe, Inglese, Matilde, Millefiorini, Enrico, Galgani, Simonetta, Zaffaroni, Mauro, Ghezzi, Angelo, Salvetti, Marco, Lus, Giacomo, Florio, Ciro, Totaro, Rocco, Granella, Franco, Vianello, Marika, Gatto, Maurizia, Di Battista, Giancarlo, Aguglia, Umberto, Logullo, Francesco Ottavio, Simone, Marta, Lucisano, Giuseppe, Iaffaldano, Pietro, and Trojano, Maria
Subjects: Adult, Male, medicine.medical_specialty, neuroinflammation, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, medicine, Humans, Disabled Persons, 030212 general & internal medicine, Prospective Studies, Risk factor, clinical trials, clinically isolated syndrome, demyelination, multiple sclerosis epidemiology, Retrospective Studies, Clinically isolated syndrome, Expanded Disability Status Scale, Proportional hazards model, business.industry, Hazard ratio, Middle Aged, Italy, Antirheumatic Agents, Cohort, Disease Progression, Settore MED/26 - Neurologia, Female, Neurology (clinical), Age of onset, business, 030217 neurology & neurosurgery, Cohort study, Follow-Up Studies
Abstract: An ever-expanding number of disease-modifying drugs for multiple sclerosis have become available in recent years, after demonstrating efficacy in clinical trials. In the real-world setting, however, disease-modifying drugs are prescribed in patient populations that differ from those included in pivotal studies, where extreme age patients are usually excluded or under-represented. In this multicentre, observational, retrospective Italian cohort study, we evaluated treatment exposure in three cohorts of patients with relapsing-remitting multiple sclerosis defined by age at onset: paediatric-onset (≤18 years), adult-onset (18–49 years) and late-onset multiple sclerosis (≥50 years). We included patients with a relapsing-remitting phenotype, ≥5 years follow-up, ≥3 Expanded Disability Status Scale (EDSS) evaluations and a first neurological evaluation within 3 years from the first demyelinating event. Multivariate Cox regression models (adjusted hazard ratio with 95% conﬁdence intervals) were used to assess the risk of reaching a first 12-month confirmed disability worsening and the risk of reaching a sustained EDSS of 4.0. The effect of disease-modifying drugs was assessed as quartiles of time exposure. We found that disease-modifying drugs reduced the risk of 12-month confirmed disability worsening, with a progressive risk reduction in different quartiles of exposure in paediatric-onset and adult-onset patients [adjusted hazard ratios in non-exposed versus exposed >62% of the follow-up time: 8.0 (3.5–17.9) for paediatric-onset and 6.3 (4.9–8.0) for adult-onset, P
Published: 2020

29. Longitudinal machine learning modeling of MS patient trajectories improves predictions of disability progression

Author: Jeannette Lechner-Scott, Bart Van Wijmeersch, Serkan Ozakbas, Maria José Sá, Vahid Shaygannejad, Marco Onofrj, Tomas Kalincik, Ludwig Kappos, Gerardo Iuliano, Patrizia Sola, Eva Havrdova, Roberto Bergamaschi, Pierre Grammond, Raed Alroughani, Jose Luis Sanchez-Menoyo, Davide Maimone, Tamara Castillo Trivio, Celia Oreja-Guevara, Aysun Soysal, Murat Terzi, Thijs Becker, Francois Grand'Maison, Jens Kuhle, Edward De Brouwer, Maria Trojano, Franco Granella, Yves Moreau, Vincent Van Pesch, Tünde Csépány, Cristina Ramo-Tello, Fraser Moore, Riadh Gouider, Liesbet M. Peeters, Cavit Boz, Claudio Solaro, Daniele Spitaleri, Sara Eichau, Oliver Gerlach, Katherine Buzzard, Elisabetta Cartechini, Eduardo Aguera-Morales, DE BROUWER, Edward, BECKER, Thijs, Moreau, Yves, Havrdova, Eva, Trojano, Maria, Eichau, Sara, Ozakbas, Serkan, Onofrj, Marco, Grammond, Pierre, Kuhle, Jens, Kappos, Ludwig, Sola, Patrizia, Cartechini, Elisabetta, Lechner-Scott, Jeannette, Alroughani, Raed, Gerlach, Oliver, Kalincik, Tomas, Granella, Franco, Grand'maison, Francois, Bergamaschi, Roberto, José Sá, Maria, VAN WIJMEERSCH, Bart, Soysal, Aysun, Sanchez-Menoyo, Jose, Solaro, Claudio, Boz, Cavit, Iuliano, Gerardo, Buzzard, Katherine, Aguera-Morales, Eduardo, Terzi, Murat, Trivio, Tamara, Spitaleri, Daniele, Van Pesch, Vincent, Shaygannejad, Vahid, Moore, Fraser, Oreja-Guevara, Celia, Maimone, Davide, Gouider, Riadh, Csepany, Tunde, Ramo-Tello, Cristina, PEETERS, Liesbet, UCL - SSS/IONS/NEUR - Clinical Neuroscience, and UCL - (SLuc) Service de neurologie
Subjects: Technology, Computer science, Health Informatics, Machine learning, computer.software_genre, THERAPY, Health informatics, 030218 nuclear medicine & medical imaging, Multiple sclerosis, 03 medical and health sciences, Engineering, 0302 clinical medicine, Computer Science, Theory & Methods, Humans, Electronic health records, Medical history, Disability progression, Engineering, Biomedical, Science & Technology, Longitudinal data, business.industry, Disease progression, MULTIPLE-SCLEROSIS, Precision medicine, Real-world data, Computer Science Applications, Clinical trial, Recurrent neural network, Recurrent neural networks, Ranking, REGISTRY, Computer Science, Computer Science, Interdisciplinary Applications, Neural Networks, Computer, Artificial intelligence, business, Life Sciences & Biomedicine, computer, Medical Informatics, 030217 neurology & neurosurgery, Software
Abstract: BACKGROUND AND OBJECTIVES: Research in Multiple Sclerosis (MS) has recently focused on extracting knowledge from real-world clinical data sources. This type of data is more abundant than data produced during clinical trials and potentially more informative about real-world clinical practice. However, this comes at the cost of less curated and controlled data sets. In this work we aim to predict disability progression by optimally extracting information from longitudinal patient data in the real-world setting, with a special focus on the sporadic sampling problem. METHODS: We use machine learning methods suited for patient trajectories modeling, such as recurrent neural networks and tensor factorization. A subset of 6682 patients from the MSBase registry is used. RESULTS: We can predict disability progression of patients in a two-year horizon with an ROC-AUC of 0.85, which represents a 32% decrease in the ranking pair error (1-AUC) compared to reference methods using static clinical features. CONCLUSIONS: Compared to the models available in the literature, this work uses the most complete patient history for MS disease progression prediction and represents a step forward towards AI-assisted precision medicine in MS. ispartof: COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE vol:208 ispartof: location:Ireland status: published
Published: 2021

30. Incidence of pregnancy and disease-modifying therapy exposure trends in women with multiple sclerosis: A contemporary cohort study

Author: Cristina Ramo-Tello, Vilija Jokubaitis, Raed Alroughani, Pamela A. McCombe, Pierre Duquette, Mark Slee, Steve Vucic, Jeannette Lechner-Scott, Olga Skibina, Klaus Gregaard Madsen, Anneke van der Walt, Pierre Grammond, Eva Havrdova, Radek Ampapa, Freek Verheul, José Luis Sánchez Menoyo, Guillermo Izquierdo, Francois Grand'Maison, Vincent Van Pesch, Murat Terzi, Alexandre Prat, Recai Turkoglu, Aysun Soysal, Eugenio Pucci, Cameron Shaw, Tomas Kalincik, Claudio Solaro, Marc Girard, Kerisha Naidoo, Patrizia Sola, Alessandra Lugaresi, Cavit Boz, Julie Prevost, Daniele Spitaleri, Ai Lan Nguyen, Dana Horakova, Javier Olascoaga, Celia Oreja-Guevara, Diana Ferraro, Michael Barnett, Helmut Butzkueven, Maria Trojano, Franco Granella, Robert Hyde, Suzanne Hodgkinson, OMÜ, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Nguyen, Ai-Lan, Havrdova, Eva Kubala, Horakova, Dana, Izquierdo, Guillermo, Kalincik, Toma, van der Walt, Anneke, Terzi, Murat, Alroughani, Raed, Duquette, Pierre, Girard, Marc, Prat, Alexandre, Boz, Cavit, Sola, Patrizia, Ferraro, Diana, Lugaresi, Alessandra, Lechner-Scott, Jeannette, Barnett, Michael, Grand'Maison, Francoi, Grammond, Pierre, Ramo-Tello, Cristina, Turkoglu, Recai, McCombe, Pamela, Pucci, Eugenio, Trojano, Maria, Granella, Franco, Spitaleri, Daniele, Van Pesch, Vincent, Soysal, Aysun, Oreja-Guevara, Celia, Verheul, Freek, Vucic, Steve, Hodgkinson, Suzanne, Slee, Mark, Ampapa, Radek, Prevost, Julie, Menoyo, Jose Luis Sanchez, Skibina, Olga, Solaro, Claudio, Olascoaga, Javier, Shaw, Cameron, Madsen, Klaus Gregaard, Naidoo, Kerisha, Hyde, Robert, Butzkueven, Helmut, and Jokubaitis, Vilija
Subjects: Adult, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Population, Exposure therapy, Clinical Neurology, Outcomes, Multiple sclerosis, Cohort Studies, 03 medical and health sciences, symbols.namesake, Young Adult, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Pregnancy, medicine, Humans, Immunologic Factors, Multiple sclerosi, 030212 general & internal medicine, Poisson regression, Registries, Young adult, education, Outcome, Retrospective Studies, education.field_of_study, Obstetrics, business.industry, Incidence (epidemiology), Incidence, Pregnancy Outcome, Retrospective cohort study, General Medicine, medicine.disease, Pregnancy Complications, Neurology, symbols, Female, Neurology (clinical), Therapy, business, 030217 neurology & neurosurgery, Cohort study, Follow-Up Studies
Abstract: Turkoglu, Recai/0000-0001-9724-851X; McCombe, Pamela/0000-0003-2704-8517; Jokubaitis, Vilija G./0000-0002-3942-4340; Oreja-Guevara, Celia/0000-0002-9221-5716; Ramo-Tello, Cristina/0000-0001-8643-5053; Vucic, Steve/0000-0002-8323-873X; Nguyen, Ai-Lan/0000-0003-0378-6005; Kalincik, Tomas/0000-0003-3778-1376; van Pesch, Vincent/0000-0003-2885-9004; Skibina, Olga/0000-0002-6275-8138; Lugaresi, Alessandra/0000-0003-2902-5589; Slee, Mark/0000-0003-4323-2453 WOS: 000459833100045 PubMed: 30623864 Background: Exposure to disease-modifying therapy (DMT) during early pregnancy in women with relapsing-remitting MS (RAMS) may be increasing. Objective: To retrospectively determine incidence of pregnancy, DMT exposure and pregnancy outcomes in women with RAMS. Methods: We identified all women with RAMS aged 15-45 years in the MSBase Registry between 2005-2016. Annualised pregnancy incidence rates were calculated using Poisson regression models. DMT exposures and pregnancy outcomes were assessed. Results: Of 9,098 women meeting inclusion criteria, 1,178 (13%) women recorded 1,521 pregnancies. The annualised incidence rate of pregnancy was 0.042 (95% CI 0.040, 0.045). A total of 635 (42%) reported pregnancies were conceived on DMT, increasing from 27% in 2006 to 62% in 2016. The median duration of DMT exposure during pregnancy was 30 days (IQR: 9, 50). There were a higher number of induced abortions on FDA pregnancy class C/D drugs compared with pregnancy class B and no DMT (p = 0.010); but no differences in spontaneous abortions, term or preterm births. Conclusions: We report low pregnancy incidence rates, with increasing number of pregnancies conceived on DMT over the past 12-years. The median duration of DMT exposure in pregnancy was relatively short at one month. National Health and Medical Research Council of Australia centre for research excellence grant [1001216]; BiogenBiogen; MerckMerck & Company; NovartisNovartis; RocheRoche Holding; Sanofi-Genzyme This study was financially supported by a National Health and Medical Research Council of Australia centre for research excellence grant [1001216]. The MSBase Foundation is a not-for-profit organisation that receives support from Biogen, Merck, Novartis, Roche and Sanofi-Genzyme. The study was conducted separately and apart from the guidance of the sponsors.
Published: 2019

31. Contribution of different relapse phenotypes to disability in multiple sclerosis

Author: Tamasine Stewart, Erik van Munster, Mark Slee, Patrizia Sola, Eva Havrdova, Dana Horakova, Orla Gray, Helmut Butzkueven, Cameron Shaw, Eugenio Pucci, Michael Barnett, Csilla Rozsa, Pamelo McCombe, Vincent Van Pesch, Maria Trojano, Franco Granella, Bhim Singhal, Fraser Moore, Javier Olascoaga, Neil Shuey, Pierre Duquette, Christina Ramo, Tomas Kalincik, Marc Girard, Freek Verheul, José Luis Sánchez Menoyo, Edgardo Cristiano, Pierre Grammond, Julie Prevost, Guillermo Izquierdo, Tim Spelman, Tatjana Petkovska-Boskova, Francois Grand'Maison, Celia Oreja-Guevara, Vahid Shaygannejad, Maria Laura Saladino, Suzanne Hodgkinson, Allan G. Kermode, Norma Deri, Alexandre Prat, Raymond Hupperts, Bruce V. Taylor, Gerardo Iuliano, Daniele Spitaleri, Cavit Boz, Roberto Bergamaschi, Raed Alroughani, Radek Ampapa, Vilija Jokubaitis, Jeannette Lechner-Scott, Maria Pia Amato, Olga Skibina, Alessandra Lugaresi, Steve Vucic, Ilya Kister, Stewart, Tamasine, Spelman, Tim, Havrdova, Eva, Horakova, Dana, Trojano, Maria, Izquierdo, Guillermo, Duquette, Pierre, Girard, Marc, Prat, Alexandre, Lugaresi, Alessandra, Grand'Maison, Francoi, Grammond, Pierre, Sola, Patrizia, Shaygannejad, Vahid, Hupperts, Raymond, Alroughani, Raed, Oreja-Guevara, Celia, Pucci, Eugenio, Boz, Cavit, Lechner-Scott, Jeannette, Bergamaschi, Roberto, Van Pesch, Vincent, Iuliano, Gerardo, Ramo, Cristina, Taylor, Bruce, Slee, Mark, Spitaleri, Daniele, Granella, Franco, Verheul, Freek, Mccombe, Pamela, Hodgkinson, Suzanne, Amato, Maria Pia, Vucic, Steve, Gray, Orla, Cristiano, Edgardo, Barnett, Michael, Sanchez Menoyo, Jose Lui, van Munster, Erik, Saladino, Maria Laura, Olascoaga, Javier, Prevost, Julie, Deri, Norma, Shaw, Cameron, Singhal, Bhim, Moore, Fraser, Rozsa, Csilla, Shuey, Neil, Skibina, Olga, Kister, Ilya, Petkovska-Boskova, Tatjana, Ampapa, Radek, Kermode, Allan, Butzkueven, Helmut, Jokubaitis, Vilija, Kalincik, Toma, and MSBase Study Group
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Multiple Sclerosis, Prognosi, multiple sclerosis, Disability Evaluation, 03 medical and health sciences, 0302 clinical medicine, cohort studies, Recurrence, Internal medicine, medicine, Humans, Disabled Persons, Prospective Studies, Prospective cohort study, Expanded Disability Status Scale, business.industry, Incidence (epidemiology), Multiple sclerosis, Interferon-beta, Middle Aged, Prognosis, medicine.disease, Functional system, Phenotype, Confidence interval, relapse phenotype, 030104 developmental biology, Neurology, multiple sclerosi, Chronic Disease, Disease Progression, Physical therapy, Female, observational study, outcome research, Neurology (clinical), business, 030217 neurology & neurosurgery, cohort studie, Cohort study
Abstract: Objective: This study evaluated the effect of relapse phenotype on disability accumulation in multiple sclerosis. Methods: Analysis of prospectively collected data was conducted in 19,504 patients with relapse-onset multiple sclerosis and minimum 1-year prospective follow-up from the MSBase cohort study. Multivariable linear regression models assessed associations between relapse incidence, phenotype and changes in disability (quantified with Expanded Disability Status Scale and its Functional System scores). Sensitivity analyses were conducted. Results: In 34,858 relapses recorded during 136,462 patient-years (median follow-up 5.9 years), higher relapse incidence was associated with greater disability accumulation (β = 0.16, p Conclusion: Relapses are associated with accumulation of neurological disability. Relapses in pyramidal, cerebellar and bowel/bladder systems have the greatest association with disability change. Therefore, prevention of these relapses is an important objective of disease-modifying therapy. The differential impact of relapse phenotypes on disability outcomes could influence management of treatment failure in multiple sclerosis.
Published: 2016

32. Silent lesions on MRI imaging - Shifting goal posts for treatment decisions in multiple sclerosis

Author: Francois Grand'Maison, Raed Alroughani, Jeannette Lechner-Scott, Vincent Van Pesch, Michael Barnett, Maria Trojano, Franco Granella, Raymond Hupperts, Cavit Boz, Jose Luis Sanchez-Menoyo, Daniele Spitaleri, Eugenio Pucci, Patrizia Sola, Pierre Grammond, Pierre Duquette, Tomas Kalincik, Helmut Butzkueven, Marc Girard, Steve Vucic, Tim Spelman, Guillermo Izquierdo, Alessandra Lugaresi, Myintzu Min, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Min, Myintzu, Spelman, Tim, Lugaresi, Alessandra, Boz, Cavit, Spitaleri, Daniele LA, Pucci, Eugenio, Grand'Maison, Francoi, Granella, Franco, Izquierdo, Guillermo, Butzkueven, Helmut, Sanchez-Menoyo, Jose Lui, Barnett, Michael, Girard, Marc, Trojano, Maria, Grammond, Pierre, Duquette, Pierre, Sola, Patrizia, Alroughani, Raed, Hupperts, Raymond, Vucic, Steve, Kalincik, Toma, Van Pesch, Vincent, and Lechner-Scott, Jeannette
Subjects: Adult, Male, medicine.medical_specialty, Treatment response, Databases, Factual, Mri imaging, Clinical Decision-Making, Drug Substitution, subclinical lesions, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, 0302 clinical medicine, medicine, Humans, Disease-modifying therapy, magnetic resonance imaging, 030212 general & internal medicine, medicine.diagnostic_test, business.industry, Multiple sclerosis, Brain, Magnetic resonance imaging, Middle Aged, medicine.disease, Clinical neurology, Neurology, Current practice, Female, Neurology (clinical), Treatment decision making, Radiology, business, 030217 neurology & neurosurgery
Abstract: Background: The current best practice suggests yearly magnetic resonance imaging (MRI) to monitor treatment response in multiple sclerosis (MS) patients. Objective: To evaluate the current practice of clinicians changing MS treatment based on subclinical new MRI lesions alone. Methods: Using MSBase, an international MS patient registry with MRI data, we analysed the probability of treatment change among patients with clinically silent new MRI lesions. Results: A total of 8311 MRI brain scans of 4232 patients were identified. Around 26.9% (336/1247) MRIs with one new T2 lesion were followed by disease-modifying therapy (DMT) change, increasing to 50.2% (129/257) with six new T2 lesions. DMT change was twice as likely with new T1 contrast enhancing compared to new T2 lesions odds ratio (OR): 2.43, 95% confidence interval (CI): 2.00–2.96 vs OR: 1.26 (95% CI: 1.22–1.29). DMT change with new MRI lesions occurred most frequently with ‘injectable’ DMTs. The probability of switching therapy was greater only after high-efficacy therapies became available in 2007 (after, OR: 1.43, 95% CI: 1.28–1.59 vs before, OR: 0.98, 95% CI: 0.520–1.88). Conclusion: MS clinicians rely increasingly on MRI alone in their treatment decisions, utilizing low thresholds (1 new T2 lesion) for optimizing MS therapy. This signals a shift towards no evidence of disease activity (NEDA)-3 since high-efficacy therapies became available.
Published: 2018

33. Predictors of relapse and disability progression in MS patients who discontinue disease-modifying therapy

Author: Suzanne Hodgkinson, Ludwig Kappos, Francesco Patti, Patrizia Sola, Murat Terzi, Ilya Kister, Raed Alroughani, Eugenio Pucci, Raymond Hupperts, Diana Ferraro, Pierre Grammond, Francois Grand'Maison, Jeannette Lechner-Scott, Claudio Solaro, Alessandra Lugaresi, Guillermo Izquierdo, Tim Spelman, Helmut Butzkueven, Pierre Duquette, Maria Trojano, Cavit Boz, Kister, Ilya, Spelman, Tim, Patti, Francesco, Duquette, Pierre, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Grammond, Pierre, Sola, Patrizia, Ferraro, Diana, Grand'Maison, Francoi, Alroughani, Raed, Terzi, Murat, Boz, Cavit, Hupperts, Raymond, Lechner-Scott, Jeannette, Kappos, Ludwig, Pucci, Eugenio, Hodgkinson, Suzanne, Solaro, Claudio, Butzkueven, Helmut, and Ondokuz Mayıs Üniversitesi
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Multiple sclerosis, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Natalizumab, Recurrence, Risk Factors, Internal medicine, Disability, Disease modifying therapy, Observational cohort study, Relapse, Neurology, Neurology (clinical), Medicine, Humans, Immunologic Factors, Multiple sclerosi, 030212 general & internal medicine, Glatiramer acetate, business.industry, McDonald criteria, medicine.disease, Prognosis, Fingolimod, Discontinuation, Cohort, Disease Progression, Patient Compliance, Female, business, 030217 neurology & neurosurgery, medicine.drug, Cohort study, Follow-Up Studies
Abstract: Lugaresi, Alessandra/0000-0003-2902-5589; Ferraro, Diana/0000-0003-4818-3806; patti, francesco/0000-0002-6923-0846; Kister, Ilya/0000-0003-3549-949X; Spelman, Tim/0000-0001-9204-3216 WOS: 000439672500016 PubMed: 30103975 Background: Discontinuation of disease-modifying therapies (DMTs) for MS is common. MSBase, a large global observational registry, affords a unique opportunity to investigate predictors of 'post-DMT' relapses and confirmed disability progression (CDP) in a diverse group of patients exposed to different DMTs. Materials/methods: Main inclusion criteria: clinician-confirmed MS diagnosis (2010 McDonald criteria); age 18 at index DMT start; >= 12 months on index DMT prior to discontinuation; >= 24 months of follow-up post-discontinuation; did not restart DMT for >= 6 months. Predictors of time to first relapse and 3-month CDP were analyzed using Cox proportional hazards regression adjusted for age, gender, baseline EDSS, EDSS stability and relapse-free period for >= 1 year prior to discontinuation, calendar epoch, index DMT and reason for discontinuation. Results: 4842 patients (74.2% female) from 20 MSBase Centers met our inclusion criteria. 3556 (73%) discontinued one of IFN beta preparations, 849 (18%) - glatiramer acetate, 308 (6%) - natalizumab and 129 (3%) - fingolimod; other DMTs were excluded because too few records were available. Overall post-discontinuation annualized relapse rate (95% CI) was 0.224 (0.219, 0.229) and CDP rate was 8.23 (7.72, 8.76) per 100 person years. Risk of post-DMT relapse was higher in younger patients, female patients, those with moderate disability and a relapse within 1 year of discontinuation. Hazard of CDP increased with increasing disability at baseline and disease progression within 3 years prior to stopping DMT. Of all the DMTs, only natalizumab was associated with increased risk of both post-DMT relapse and CDP. Conclusions: Knowledge of post-DMT relapse and disability progression rates and predictors of post-DMT disease activity allows for a more informed discussion of DMT discontinuation in those patients who are considering this option. Bayer ScheringBayer AG; Biogen IdecBiogen; Merck SeronoMerck SeronoMerck & Company; Novartis Pharma; SanofiSanofi-Aventis No targeted funding was provided for this study. MSBase Foundation is a not-for-profit organization that receives support from Bayer Schering, Biogen Idec, Merck Serono, Novartis Pharma, and Sanofi.
Published: 2018

34. First-line disease-modifying drugs in relapsing-remitting multiple sclerosis: an Italian real-life multicenter study on persistence

Author: Sara Montepietra, Diana Ferraro, Anna Maria Simone, Valentina Camera, Paolo Immovilli, Mario Santangelo, Patrizia Sola, Matteo Foschi, Ilaria Pesci, Luisa Caniatti, Alessandra Lugaresi, Erica Curti, Luisa Motti, Enrico Montanari, S. Malagù, W. Neri, Francesca Vitetta, Silvia Strumia, Angelica Guareschi, Eleonora Baldi, Veria Vacchiano, Franco Granella, Ferraro, Diana, Camera, Valentina, Baldi, Eleonora, Vacchiano, Veria, Curti, Erica, Guareschi, Angelica, Malagù, Susanna, Montepietra, Sara, Strumia, Silvia, Santangelo, Mario, Caniatti, Luisa, Foschi, Matteo, Lugaresi, Alessandra, Granella, Franco, Pesci, Ilaria, Motti, Luisa, Neri, Walter, Immovilli, Paolo, Montanari, Enrico, Vitetta, Francesca, Simone, Anna Maria, Sola, Patrizia, and DIPARTIMENTO DI SCIENZE BIOMEDICHE E NEUROMOTORIE
Subjects: Persistence (psychology), Oral, Adult, Male, medicine.medical_specialty, Multiple Sclerosis, First line, Disease-Modifying Drugs, Administration, Oral, Disease-Modifying Drug, Disease, disease-modifying drugs, Injections, Medication Adherence, Persistence, Injectable, Multiple sclerosis, 03 medical and health sciences, oral, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Multiple Sclerosi, medicine, Humans, 030212 general & internal medicine, Prospective Studies, injectable, business.industry, General Medicine, persistence, Middle Aged, medicine.disease, Multicenter study, Relapsing remitting, Italy, Antirheumatic Agents, Female, business, 030217 neurology & neurosurgery
Abstract: none 22 no OBJECTIVE: The introduction of oral disease-modifying drugs (DMDs) in addition to the available, injectable, ones for Relapsing-Remitting Multiple Sclerosis (RRMS) could be expected to improve medication persistence due to a greater acceptability of the route of administration. Aim of the study was to compare the proportion of patients discontinuing injectable DMDs (interferon beta 1a/1b, pegylated interferon, glatiramer acetate) with those discontinuing oral DMDs (dimethylfumarate and teriflunomide) during an observation period of at least 12 months. Secondary aims were to compare the time to discontinuation and the reasons for discontinuation between the two groups and to explore the demographic and clinical factors associated with DMD discontinuation. METHODS: In this prospective, multi-center, real-life observational study, patients commencing any first-line DMD between January 1st 2015 and July 31st 2016 were enrolled and followed-up for at least twelve months or until the drug was discontinued. RESULTS: Of the 520 included patients, 262 (49.6%) started an injectable, and 258 (50.4%) an oral DMD. There was no difference in the proportion of patients on oral (nr = 62, 24%) or on injectable (nr = 60, 23%) DMDs discontinuing treatment, the most frequent reason being adverse events/side-effects. Higher baseline EDSS scores and younger age increased the odds of treatment withdrawal. Time to treatment discontinuation was not different between the two groups and was not influenced by the initiated DMD (oral versus injectable), even after adjustment for baseline differences. CONCLUSION: The sole route of administration (i.e. oral versus injectable) was not a significant predictor of persistence with first-line DMDs in RRMS. none Ferraro, Diana; Camera, Valentina; Baldi, Eleonora; Vacchiano, Veria; Curti, Erica; Guareschi, Angelica; Malagù, Susanna; Montepietra, Sara; Strumia, Silvia; Santangelo, Mario; Caniatti, Luisa; Foschi, Matteo; Lugaresi, Alessandra; Granella, Franco; Pesci, Ilaria; Motti, Luisa; Neri, Walter; Immovilli, Paolo; Montanari, Enrico; Vitetta, Francesca; Simone, Anna Maria; Sola, Patrizia Ferraro, Diana; Camera, Valentina; Baldi, Eleonora; Vacchiano, Veria; Curti, Erica; Guareschi, Angelica; Malagù, Susanna; Montepietra, Sara; Strumia, Silvia; Santangelo, Mario; Caniatti, Luisa; Foschi, Matteo; Lugaresi, Alessandra; Granella, Franco; Pesci, Ilaria; Motti, Luisa; Neri, Walter; Immovilli, Paolo; Montanari, Enrico; Vitetta, Francesca; Simone, Anna Maria; Sola, Patrizia
Published: 2018

35. Long-term disability trajectories in primary progressive MS patients: A latent class growth analysis

Author: Raed Alroughani, Maria Pia Amato, Patrizia Sola, Francois Grand'Maison, Eva Havrdova, Pierre Grammond, Ricardo Fernandez Bolanos, Murat Terzi, Bhim Singhal, Tomas Kalincik, Alessandra Lugaresi, Marc Girard, Jeannette Lechner-Scott, Dana Horakova, Freek Verheul, Alexandre Prat, Thor Petersen, Vahid Shaygannejad, Raymond Hupperts, Vilija Jokubaitis, Guillermo Izquierdo, Daniele Spitaleri, Jose Luis Sanchez-Menoyo, Maria Trojano, Franco Granella, Helmut Butzkueven, Mark Slee, Seyed Aidin Sajedi, Cavit Boz, Maria Pia Sormani, Pierre Duquette, Cristina Ramo, Eugenio Pucci, Alessio Signori, Celia Oreja-Guevara, Roberto Bergamaschi, Nastaran Majdinasab, Vincent Van Pesch, Bruce V. Taylor, Stella Hughes, Gerardo Iuliano, Maria Edite Rio, Ondokuz Mayıs Üniversitesi, Signori, Alessio, Izquierdo, Guillermo, Lugaresi, Alessandra, Hupperts, Raymond, Grand'Maison, Francoi, Sola, Patrizia, Horakova, Dana, Havrdova, Eva, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Boz, Cavit, Grammond, Pierre, Terzi, Murat, Singhal, Bhim, Alroughani, Raed, Petersen, Thor, Ramo, Cristina, Oreja-Guevara, Celia, Spitaleri, Daniele, Shaygannejad, Vahid, Butzkueven, Helmut, Kalincik, Toma, Jokubaitis, Vilija, Slee, Mark, Fernandez Bolaños, Ricardo, Sanchez-Menoyo, Jose Lui, Pucci, Eugenio, Granella, Franco, Lechner-Scott, Jeannette, Iuliano, Gerardo, Hughes, Stella, Bergamaschi, Roberto, Taylor, Bruce, Verheul, Freek, Edite Rio, Maria, Amato, Maria Pia, Sajedi, Seyed Aidin, Majdinasab, Nastaran, Van Pesch, Vincent, Sormani, Maria Pia, and Trojano, Maria
Subjects: 0301 basic medicine, Male, Pediatrics, Delayed Diagnosis, Placebo-controlled study, Disease, Disability Evaluation, Primary progressive multiple sclerosis, 0302 clinical medicine, Longitudinal Studies, Prospective Studies, Registries, Prospective cohort study, Age Factors, clinical trial, Middle Aged, Multiple Sclerosis, Chronic Progressive, Prognosis, Latent class model, Natural history, Neurology, Latent Class Analysis, Disease Progression, Female, Adult, medicine.medical_specialty, Primary Progressive Multiple Sclerosis, 03 medical and health sciences, Primary progressive multiple sclerosis, clinical trials, disability, heterogeneity, long-term, trajectories, Sex Factors, medicine, Humans, Disabled Persons, long-term, clinical trials, business.industry, Multiple sclerosis, Bayes Theorem, Long term disability, medicine.disease, Primary progressive multiple sclerosi, 030104 developmental biology, disability, Physical therapy, Neurology (clinical), heterogeneity, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Signori, Alessio/0000-0001-6289-9144; Sajedi, Seyed Aidin/0000-0002-6704-9787; Jokubaitis, Vilija G./0000-0002-3942-4340; Shaygannejad, Vahid/0000-0002-6226-0161; Oreja-Guevara, Celia/0000-0002-9221-5716; amato, Maria Pia/0000-0003-3325-3760; Lugaresi, Alessandra/0000-0003-2902-5589; Majdinasab, Nastaran/0000-0001-5163-7210; Kalincik, Tomas/0000-0003-3778-1376; Butzkueven, Helmut/0000-0003-3940-8727; van Pesch, Vincent/0000-0003-2885-9004; pucci, eugenio/0000-0001-7606-7330; Petersen, Thor/0000-0001-5633-2600; Prat, Alexandre/0000-0001-6188-0580; Sanchez Menoyo, Jose Luis/0000-0003-2634-8294; Slee, Mark/0000-0003-4323-2453; SORMANI, MARIA PIA/0000-0001-6892-104X; Trojano, Maria/0000-0002-6329-8946 WOS: 000432098100013 PubMed: 28382837 Background: Several natural history studies on primary progressive multiple sclerosis (PPMS) patients detected a consistent heterogeneity in the rate of disability accumulation. Objectives: To identify subgroups of PPMS patients with similar longitudinal trajectories of Expanded Disability Status Scale (EDSS) over time. Methods: All PPMS patients collected within the MSBase registry, who had their first EDSS assessment within 5 years from onset, were included in the analysis. Longitudinal EDSS scores were modeled by a latent class mixed model (LCMM), using a nonlinear function of time from onset. LCMM is an advanced statistical approach that models heterogeneity between patients by classifying them into unobserved groups showing similar characteristics. Results: A total of 853 PPMS (51.7% females) from 24 countries with a mean age at onset of 42.4 years (standard deviation (SD): 10.8 years), a median baseline EDSS of 4 (interquartile range (IQR): 2.5-5.5), and 2.4 years of disease duration (SD: 1.5 years) were included. LCMM detected three different subgroups of patients with a mild (n = 143; 16.8%), moderate (n = 378; 44.3%), or severe (n = 332; 38.9%) disability trajectory. The probability of reaching EDSS 6 at 10 years was 0%, 46.4%, and 81.9% respectively. Conclusion: Applying an LCMM modeling approach to long-term EDSS data, it is possible to identify groups of PPMS patients with different prognosis. MSBase Foundation; Merck SeronoMerck SeronoMerck & Company; BiogenBiogen; Novartis Pharma; Bayer ScheringBayer AG; Sanofi-AventisSanofi-Aventis; BioCSL The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was funded by the MSBase Foundation. The MSBase Foundation is a not-for-profit organization that receives support from Merck Serono, Biogen, Novartis Pharma, Bayer Schering, Sanofi-Aventis and BioCSL. The study was conducted separately and apart from the guidance of the sponsors.
Published: 2017

36. Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study

Author: Murat Terzi, Eugenio Pucci, Pamela A. McCombe, Alasdair Coles, Dana Horakova, Csilla Rozsa, Cavit Boz, Alessandra Lugaresi, Pierre Duquette, Michael Hutchinson, Michael Barnett, Raed Alroughani, Neil Robertson, Javier Olascoaga, Jeannette Lechner-Scott, Steve Vucic, Alexandre Prat, Patrizia Sola, Pierre Grammond, Guillermo Izquierdo, Maria Trojano, Franco Granella, Neil J Scolding, Raymond Hupperts, Vincent Van Pesch, Vilija Jokubaitis, J William L Brown, Mark Slee, Tünde Csépány, Daniele Spitaleri, Tim Spelman, Jose Luis Sanchez-Menoyo, Tjalf Ziemssen, Owen R Pearson, Tomas Kalincik, Marc Girard, Claire M Rice, Eva Havrdova, Suzanne Hodgkinson, Cristina Ramo, Alastair Wilkins, Helmut Butzkueven, Francois Grand'Maison, Edgardo Cristiano, Magdolna Simó, Radek Ampapa, Mark Willis, Freek Verheul, Roberto Bergamaschi, Christopher McGuigan, OMÜ, Brown, Will [0000-0002-7737-5834], Coles, Alasdair [0000-0003-4738-0760], Apollo - University of Cambridge Repository, MUMC+: MA Med Staf Spec Neurologie (9), RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Klinische Neurowetenschappen, Kalincik, Toma, Brown, J William L, Robertson, Neil, Willis, Mark, Scolding, Neil, Rice, Claire M, Wilkins, Alastair, Pearson, Owen, Ziemssen, Tjalf, Hutchinson, Michael, Mcguigan, Christopher, Jokubaitis, Vilija, Spelman, Tim, Horakova, Dana, Havrdova, Eva, Trojano, Maria, Izquierdo, Guillermo, Lugaresi, Alessandra, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Grammond, Pierre, Alroughani, Raed, Pucci, Eugenio, Sola, Patrizia, Hupperts, Raymond, Lechner-Scott, Jeannette, Terzi, Murat, Van Pesch, Vincent, Rozsa, Csilla, Grand'Maison, Françoi, Boz, Cavit, Granella, Franco, Slee, Mark, Spitaleri, Daniele, Olascoaga, Javier, Bergamaschi, Roberto, Verheul, Freek, Vucic, Steve, Mccombe, Pamela, Hodgkinson, Suzanne, Sanchez-Menoyo, Jose Lui, Ampapa, Radek, Simo, Magdolna, Csepany, Tunde, Ramo, Cristina, Cristiano, Edgardo, Barnett, Michael, Butzkueven, Helmut, and Coles, Alasdair
Subjects: Oncology, Adult, Male, medicine.medical_specialty, PLACEBO-CONTROLLED TRIAL, ORAL FINGOLIMOD, Antibodies, Monoclonal, Humanized, Klinikai orvostudományok, Cohort Studies, REGRESSION-MODEL, 03 medical and health sciences, Disability Evaluation, Young Adult, 0302 clinical medicine, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Fingolimod Hydrochloride, medicine, Clinical endpoint, SWITCH, Humans, Immunologic Factors, 030212 general & internal medicine, Alemtuzumab, Expanded Disability Status Scale, business.industry, Neurology (clinical), multiple sclerosis, prognosis, Multiple sclerosis, Hazard ratio, MS, Interferon-beta, Orvostudományok, medicine.disease, R1, Fingolimod, Databases, Bibliographic, Treatment Outcome, Immunology, Female, Neurology (clinical), business, CONTROLLED PHASE-3 TRIAL, 030217 neurology & neurosurgery, medicine.drug
Abstract: Lugaresi, Alessandra/0000-0003-2902-5589; McCombe, Pamela/0000-0003-2704-8517; Jokubaitis, Vilija G./0000-0002-3942-4340; Ziemssen, Tjalf/0000-0001-8799-8202; Slee, Mark/0000-0003-4323-2453; Havrdova, Eva Kubala/0000-0002-9543-4359; Horakova, Dana/0000-0003-1915-0036; van Pesch, Vincent/0000-0003-2885-9004; pucci, eugenio/0000-0001-7606-7330; Trojano, Maria/0000-0002-6329-8946; Sanchez Menoyo, Jose Luis/0000-0003-2634-8294; Brown, William/0000-0002-7737-5834; Rice, Claire/0000-0002-9851-4426; Scolding, Neil/0000-0001-9177-1043; Kalincik, Tomas/0000-0003-3778-1376; Butzkueven, Helmut/0000-0003-3940-8727; Vucic, Steve/0000-0002-8323-873X WOS: 000396336600016 PubMed: 28209331 Background Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years. Methods In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts. Longitudinal clinical data were obtained from 71 MSBase centres in 21 countries and from six non-MSBase centres in the UK and Germany between Nov 1, 2015, and June 30, 2016. Key inclusion criteria were a diagnosis of definite relapsing-remitting multiple sclerosis, exposure to one of the study therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Expanded Disability Status Scale (EDSS) score 6.5 or lower, and no more than 10 years since the first multiple sclerosis symptom. The primary endpoint was annualised relapse rate. The secondary endpoints were cumulative hazards of relapses, disability accumulation, and disability improvement events. We compared relapse rates with negative binomial models, and estimated cumulative hazards with conditional proportional hazards models. Findings Patients were treated between Aug 1, 1994, and June 30, 2016. The cohorts consisted of 189 patients given alemtuzumab, 2155 patients given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab. Alemtuzumab was associated with a lower annualised relapse rate than interferon beta (0.19 [95% CI 0.14-0.23] vs 0.53 [0.46-0.61], p
Published: 2017

37. Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis

Author: Helmut Butzkueven, Guillermo Izquierdo, Alexandre Prat, Jeannette Lechner-Scott, Raymond Hupperts, Pierre Duquette, Vilija Jokubaitis, Tim Spelman, Mark Slee, Alessandra Lugaresi, Csilla Rozsa, Francois Grand'Maison, Roberto Bergamaschi, Vincent Van Pesch, Pierre Grammond, Raed Alroughani, Nathaniel Lizak, Eugenio Pucci, Dana Horakova, Norma Deri, Eva Havrdova, Javier Olascoaga, Tomas Kalincik, Marc Girard, Suzanne Hodgkinson, Gerardo Iuliano, Maria Pia Amato, Patrizia Sola, Celia Oreja-Guevara, Cavit Boz, Daniele Spitaleri, Freek Verheul, Shlomo Flechter, Cristina Ramo, Edgardo Cristiano, Maria Trojano, Franco Granella, Lizak, Nathaniel, Lugaresi, Alessandra, Alroughani, Raed, Lechner-Scott, Jeannette, Slee, Mark, Havrdova, Eva, Horakova, Dana, Trojano, Maria, Izquierdo, Guillermo, Duquette, Pierre, Girard, Marc, Prat, Alexandre, Grammond, Pierre, Hupperts, Raymond, Grand'Maison, Francoi, Sola, Patrizia, Pucci, Eugenio, Bergamaschi, Roberto, Oreja-Guevara, Celia, Pesch, Vincent Van, Ramo, Cristina, Spitaleri, Daniele, Iuliano, Gerardo, Boz, Cavit, Granella, Franco, Olascoaga, Javier, Verheul, Freek, Rozsa, Csilla, Cristiano, Edgardo, Flechter, Shlomo, Hodgkinson, Suzanne, Amato, Maria Pia, Deri, Norma, Jokubaitis, Vilija, Spelman, Tim, Butzkueven, Helmut, Kalincik, Toma, and MSBase Study Group
Subjects: Oncology, Male, medicine.medical_specialty, Cohort Studies, Immunomodulation, 03 medical and health sciences, Disability Evaluation, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, Arts and Humanities (miscellaneous), Internal medicine, medicine, Humans, Disabled Persons, 030212 general & internal medicine, Survival analysis, Expanded Disability Status Scale, business.industry, Multiple sclerosis, Disease progression, medicine.disease, Clinical trial, Psychiatry and Mental health, Clinical research, Physical therapy, Disease Progression, Surgery, Observational study, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Cohort study
Abstract: Objective To evaluate variability and predictability of disability trajectories in moderately advanced and advanced multiple sclerosis (MS), and their modifiability with immunomodulatory therapy. Methods The epochs between Expanded Disability Status Scale (EDSS) steps 3-6, 4-6 and 6-6.5 were analysed. Patients with relapse-onset MS and having reached 6-month confirmed baseline EDSS step (3/4/6) were identified in MSBase, a global observational MS cohort study. We used multivariable survival models to examine the impact of disease-modifying therapy, clinical and demographic factors on progression to the outcome EDSS step (6/6.5). Sensitivity analyses with varying outcome definitions and inclusion criteria were conducted. Results For the EDSS 3-6, 4-6 and 6-6.5 epochs, 1560, 1504 and 1231 patients were identified, respectively. Disability trajectories showed large coefficients of variance prebaseline (0.92-1.11) and postbaseline (2.15-2.50), with no significant correlations. The probability of reaching the outcome step was not associated with prebaseline variables, but was increased by higher relapse rates during each epoch (HRs 1.58-3.07; p
Published: 2017

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