Search

Your search keyword '"Gray, O"' showing total 21 results
Start Over Author "Gray, O" Database OpenAIRE
21 results on '"Gray, O"'

1. Early non-disabling relapses are associated with a higher risk of disability accumulation in people with relapsing-remitting multiple sclerosis

Author

Coles, A., Daruwalla, C., Shaygannejad, V., Ozakbas, S., Havrdova, E. K., Alroughani, R., Patti, F., Onofrj, M., Eichau, S., Girard, M., Grand'Maison, F., Yamout, B., Sajedi, S. A., Amato, M. P., Altintas, A., Skibina, O., Grammond, P., Butzkueven, H., Maimone, D., Lechner-Scott, J., Soysal, A., John, N., Gerlach, O., Iuliano, G., Foschi, M., Van Pesch, V., Cartechini, E., Kuhle, J., Sa, M. J., Kermode, A., Gouider, R., Hodgkinson, S., McCombe, P., Sanchez-Menoyo, J. L., Singhal, B., Blanco, Y., Hughes, S., McGuigan, C., Taylor, B., Habek, M., Al-Asmi, A., Mihaela, S., Castillo Trivino, T., Al-Harbi, T., Rojas, J. I., Gray, O., Khurana, D., Van Wijmeersch, B., Kalincik, T., and Brown, J. W. L.

Published
2022

2. A non-inferiority study of rituximab versus ocrelizumab in relapsing-remitting multiple sclerosis

Author

Skibina, O., Msbase and Danish Sclerosis Registry Study Grp, Msbase and Danish Sclerosis Registry Study Grp, Kalincik, T., Magyari, M., Gray, O., Sellebjerg, F., Soysal, A., Grand'Maison, F., Grammond, P., John, N., Van Hijfte, L., Laureys, G., Terzi, M., Kuhle, J., Lechner-Scott, J., Butzkueven, H., Van der Walt, A., Buzzard, K., Ozakbas, S., Alroughani, R., Boz, C., MacDonnell, G., Hughes, S., and Roos, I.

Published
2022

4. Evaluation of common criteria of progression of disability in a large observational cohort

Author

Kalincik, T., Jokubaitis, V., Spelman, T., Horakova, D., Havrdova, E., Trojano, M., Izquierdo, G., Girard, M., Duquette, P., Lugaresi, A., Grand Maison, F., Grammond, P., Hupperts, R., Eva Kubala Havrdova, Pucci, E., Boz, C., Bergamaschi, R., Lechner-Scott, J., Alroughani, R., Pesch, V., Iuliano, G., Rio, M., Fernandez-Bolanos, R., Ramo, C., Terzi, M., Petersen, T., Slee, M., Spitaleri, D., Amato, M. P., Verheul, F., Cristiano, E., Sanchez-Menoyo, J., Fiol, M., Gray, O., Cabrera-Gomez, J., Hodgkinson, S., Barnett, M., Saladino, M., Vucic, S., Shaw, C., Moore, F., Munster, E., Rozsa, C., Mccombe, P., Butzkueven, H., T. Kalincik, V. Jokubaiti, T. Spelman, D. Horakova, E. Havrdova, M. Trojano, G. Izquierdo, M. Girard, P. Duquette, A. Lugaresi, F. Grand’Maison, P. Grammond, R. Huppert, C. Oreja-Guevara, E. Pucci, C. Boz, R. Bergamaschi, J. Lechner-Scott, L. Alroughani, V.Van Pesch, G. Iuliano, M. Rio, R. Fernande-Bolano, C. Ramo, M. Terzi, T. Petersen, M. Slee, D. Spitalieri, MP Amato, F Verheul, E. Cristiano, J. Sanchez-Menoyo, M. Fiol, O. Gray, JA. Cabrera-Gomez, S. Hodgkinson, M. Barnett, M. Saladino, S. Vucic, C. Shaw, F. Moore, E Van Muster, C. Rozsa, P. McCombe, and H. Butzkueven

Subjects
multiple sclerosis, clinical course, progression, clinical evaluation, prognostic factors
Published
2014

5. A primary care-based needs assessment of people with multiple sclerosis

Author

MacLurg, K, Reilly, P, Hawkins, S, Gray, O, Evason, E, and Whittington, D

Subjects
Adult, Aged, 80 and over, Male, Multiple Sclerosis, Health Status, Northern Ireland, Middle Aged, Patient Acceptance of Health Care, Community Health Nursing, Original Papers, Health Services Accessibility, Cross-Sectional Studies, Quality of Life, Humans, Female, Family Practice, Respite Care, Attitude to Health, Needs Assessment, Physical Therapy Modalities, Aged
Abstract

Multiple sclerosis (MS) is a common cause of chronic progressive neurological disability where reduction in quality of life is an important feature. Many GPs have MS patients with a range of disabilities. Little is known about the supply of medical and community services and how this compares with demand.We aim to describe a community based sample of MS patients and investigate how disease characteristics, benefits, services accessed and perceived needs relate to sense of wellbeing.Cross-sectional survey.Participants were recruited from a representative network of 30 GP practices across Northern Ireland.MS patients answered a professionally administered questionnaire and agreed to their medical records being examined. Information was collected about their medical condition, sociodemographic characteristics, receipt of benefits and services, perceived needs and sense of wellbeing.Of the 149 participants, 23% were mildly affected (Kurtzke's Expanded Disability Status Scale [EDSS] 0-4.5), 41% were moderately disabled (EDSS 5.0-6.5) and 36% were severely disabled (EDSS 7.0-9.5). Disability was related to employment, receipt of benefits and services. Physiotherapy was a commonly perceived need. Other perceived needs differed between the moderately and severely disabled groups. Scores relating to wellbeing were related to disability and perceived needs.The relationship between use of medical and community services and disability is important for planning service provision. We have shown that perceived needs are related to wellbeing. In a progressive illness these developing needs could be anticipated.

Published
2005

7. Paediatrics

Author

Gray, O P

Subjects
Book Review
Published
1982

9. Defining secondary progressive multiple sclerosis

Author

Lorscheider, J., Buzzard, K., Jokubaitis, V., Spelman, T., Havrdova, E., Horakova, D., Trojano, M., Izquierdo, G., Girard, M., Duquette, P., Prat, A., Lugaresi, A., Grand Maison, F., Grammond, P., Hupperts, R., Alroughani, R., Sola, P., Boz, C., Terzi, M., Pucci, E., Lechner-Scott, J., Bergamaschi, R., Eva Kubala Havrdova, Iuliano, G., Pesch, V., Bolanos, R. F., Granella, F., Rio, M. E., Ramo, C., Spitaleri, D. L., Petersen, T., Slee, M., Verheul, F., Ampapa, R., Amato, M. P., Mccombe, P., Vucic, S., Menoyo, J. L. S., Cristiano, E., Barnett, M., Hodgkinson, S., Cabrera-Gomez, J. A., Olascoaga, J., Saladino, M. L., Flechter, S., Gray, O., Deri, N., Butzkueven, H., Kalincik, T., and Sbase Study Grp, M.

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

Author

Diouf, I, Malpas, C, Horakova, D, Havrdova, EK, Patti, F, Shaygannejad, V, Ozakbas, S, Izquierdo, G, Eichau, S, Zakaria, M, Onofrj, M, Lugaresi, A, Alroughani, R, Prat, A, Girard, M, Duquette, P, Terzi, M, Boz, C, Grand'Maison, F, Hamdy, S, Sola, P, Ferraro, D, Grammond, P, Turkoglu, R, Butzkueven, H, Yamout, B, Altintas, A, Van Pesch, V, Maimone, D, Lechner-Scott, J, Bergamaschi, R, Karabudak, R, Giuliano, F, Mcguigan, C, Cartechini, E, Barnett, M, Hughes, S, Sa, M, Kappos, L, Ramo-Tello, C, Cristiano, E, Hodgkinson, S, Spitaleri, D, Soysal, A, Petersen, T, Slee, M, Butler, E, Granella, F, Verheul, F, Mccombe, P, Ampapa, R, Skibina, O, Prevost, J, Sinnige, LGF, Sanchez-Menoyo, JL, Vucic, S, Laureys, G, Van Hijfte, L, Khurana, D, Macdonell, R, Castillo-Trivino, T, Gray, O, Aguera, E, Kister, I, Shaw, C, Deri, N, Al-Harbi, T, Fragoso, Y, Csepany, T, Sempere, A, and Kalincik, T

11. Evaluation of common criteria of progression of disability in a large observational cohort

Author

Kalincik, T., Jokubaitis, V., Spelman, T., Horakova, D., Havrdova, E., Trojano, M., Izquierdo, G., Girard, M., Duquette, P., Lugaresi, A., Grand Maison, F., Grammond, P., Hupperts, R., Eva Kubala Havrdova, Pucci, E., Boz, C., Bergamaschi, R., Lechner-Scott, J., Alroughani, R., Pesch, V., Iuliano, G., Rio, M., Fernandez-Bolanos, R., Ramo, C., Terzi, M., Petersen, T., Slee, M., Spitaleri, D., Amato, M. P., Verheul, F., Cristiano, E., Sanchez-Menoyo, J., Fiol, M., Gray, O., Cabrera-Gomez, J., Hodgkinson, S., Barnett, M., Saladino, M., Vucic, S., Shaw, C., Moore, F., Munster, E., Rozsa, C., Mccombe, P., Butzkueven, H., and Sbase Study Grp, M.

12. Effect of relapse phenotype on the accumulation of disability in relapsing-remitting multiple sclerosis

Author

Stewart, T., Jokubaitis, V., Spelman, T., Havrdova, E., Horakova, D., Trojano, M., Izquierdo, G., Girard, M., Duquette, P., Prat, A., Lugaresi, A., Grammond, P., Grand Maison, F., Sola, P., Hupperts, R., Petersen, T., Pucci, E., Bergamaschi, R., Boz, C., Eva Kubala Havrdova, Lechner-Scott, J., Alroughani, R., Ramo, C., Pesch, V., Fernandez-Bolanos, R., Iuliano, G., Rio, M. E., Granella, F., Slee, M., Verheul, F., Spitaleri, D. L. A., Amato, M. P., Hodgkinson, S., Mccombe, P., Cabrera-Gomez, J. A., Barnett, M., Flechter, S., Olascoaga, J., Vucic, S., Sanchez-Menoyo, J. L., Cristiano, E., Saladino, M. L., Moore, F., Gray, O., Shuey, N., Rozsa, C., Singhal, B., Shaw, C., Butzkueven, H., Kalincik, T., and Sbase Study Grp, M.

13. The MSBase pregnancy, neonatal outcomes, and women’s health registry

Author

Anneke van der Walt, Kerstin Hellwig, Ayse Altintas, Sara Eichau, Olga Skibina, Vilija Jokubaitis, Orla Gray, Helmut Butzkueven, Louise Rath, Raed Alroughani, Yara Dadalti Fragoso, Stella Hughes, Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Jokubaitis, V. G., Skibina, O., Alroughani, R., Butzkueven, H., Eichau, S., Fragoso, Y., Hellwig, K., Hughes, S. E., Rath, L., van der Walt, A., Gray, O., and School of Medicine

Subjects
Registry, medicine.medical_specialty, Multiple Sclerosis, Women’s Health, MSBase, lcsh:RC346-429, Study Protocol, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, medicine, Neurosciences, Neurology, lcsh:Neurology. Diseases of the nervous system, Pharmacology, 030219 obstetrics & reproductive medicine, business.industry, Multiple sclerosis, Neonatal outcomes, Women’s health, medicine.disease, Clinical neurology, Family planning, Family medicine, Neonatal Outcomes, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Background: family planning and pregnancy decisions are key considerations in the management of women with multiple sclerosis (MS), who are typically diagnosed between the ages of 20–40 years. Despite a strong evidence base that pregnancy is not harmful for women with MS, many knowledge gaps remain. These include: best management strategies through pregnancy in the era of highly effective disease-modifying therapies (DMT); foetal risks associated with DMT exposure in utero or in relation to breastfeeding; knowledge base around the use of assisted reproductive technologies; the long-term impact of pregnancy on disease outcomes, as well as the impact of long-term DMT use on women’s health and cancer risk. Methods: here, we describe the new MSBase pregnancy, neonatal outcomes and women’s health registry. We provide the rationale for, and detailed description of, the variables collected within the registry, together with data acquisition details. Conclusion: the present paper will act as a reference document for future studies., National Health and Medical Research Council of Australia; MSBase Foundation; Roche; Merck; Biogen; Novartis; Bayer-Schering; Sanofi Genzyme; Teva

Published
2021

14. Risk of secondary progressive multiple sclerosis: A longitudinal study

Author

Michael Barnett, Bhim Singhal, Maria Trojano, Franco Granella, Neil Shuey, Guillermo Izquierdo, Dana Horakova, Helmut Butzkueven, Talal Al-Harbi, Maria Laura Saladino, Cameron Shaw, Adam Fambiatos, Bart Van Wijmeersch, Serkan Ozakbas, Tünde Csépány, Freek Verheul, Cavit Boz, Tim Spelman, Pierre Duquette, Jeannette Lechner-Scott, Bassem Yamout, Roberto Bergamaschi, Vincent Van Pesch, Claudio Solaro, Edgardo Cristiano, Patrizia Sola, Vilija Jokubaitis, Jae Kwan Jun, Alessandra Lugaresi, Javier Olascoaga, Aysun Soysal, Thor Petersen, Mark Slee, Raed Alroughani, Francois Grand'Maison, Orla Gray, Tomas Kalincik, Marc Girard, Gerardo Iuliano, Anneke van der Walt, Eva Havrdova, Jose Luis Sanchez-Menoyo, Radek Ampapa, Julie Prevost, Steve Vucic, Pamela A. McCombe, Recai Turkoglu, Yara Dadalti Fragoso, Jordana Hughes, Olga Skibina, Murat Terzi, Eugenio Pucci, Diana Ferraro, Pierre Grammond, Fraser Moore, Ayse Altintas, Suzanne Hodgkinson, Youssef Sidhom, Norma Deri, Alexandre Prat, Raymond Hupperts, Daniele Spitaleri, Bruce V. Taylor, Fambiatos A., Jokubaitis V., Horakova D., Kubala Havrdova E., Trojano M., Prat A., Girard M., Duquette P., Lugaresi A., Izquierdo G., Grand'Maison F., Grammond P., Sola P., Ferraro D., Alroughani R., Terzi M., Hupperts R., Boz C., Lechner-Scott J., Pucci E., Bergamaschi R., Van Pesch V., Ozakbas S., Granella F., Turkoglu R., Iuliano G., Spitaleri D., McCombe P., Solaro C., Slee M., Ampapa R., Soysal A., Petersen T., Sanchez-Menoyo J.L., Verheul F., Prevost J., Sidhom Y., Van Wijmeersch B., Vucic S., Cristiano E., Saladino M.L., Deri N., Barnett M., Olascoaga J., Moore F., Skibina O., Gray O., Fragoso Y., Yamout B., Shaw C., Singhal B., Shuey N., Hodgkinson S., Altintas A., Al-Harbi T., Csepany T., Taylor B., Hughes J., Jun J.-K., van der Walt A., Spelman T., Butzkueven H., Kalincik T., Ondokuz Mayıs Üniversitesi, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, and UCL - (SLuc) Service de neurologie

Subjects
Adult, Male, Risk, medicine.medical_specialty, Longitudinal study, Immunologic Factors, multiple sclerosis, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Multiple Sclerosis, Relapsing-Remitting, disease modifying therapies, prognostics, Internal medicine, Severity of illness, Medicine, Humans, Longitudinal Studies, 030304 developmental biology, 0303 health sciences, business.industry, Multiple sclerosis, Disease progression, prediction, Multiple Sclerosis, Chronic Progressive, medicine.disease, SPMS, Clinical neurology, Natural history, Neurology, multiple sclerosi, disease modifying therapie, Disease Progression, Secondary progressive multiple sclerosis, Female, Neurology (clinical), business, prognostic, 030217 neurology & neurosurgery
Abstract

Turkoglu, Recai/0000-0001-9724-851X; Ferraro, Diana/0000-0003-4818-3806; McCombe, Pamela/0000-0003-2704-8517; Altintas, Ayse/0000-0002-8524-5087; Jokubaitis, Vilija G./0000-0002-3942-4340; Slee, Mark/0000-0003-4323-2453; Lugaresi, Alessandra/0000-0003-2902-5589; van Pesch, Vincent/0000-0003-2885-9004; Vucic, Steve/0000-0002-8323-873X WOS: 000481049900001 PubMed: 31397221 Background: The risk factors for conversion from relapsing-remitting to secondary progressive multiple sclerosis remain highly contested. Objective: The aim of this study was to determine the demographic, clinical and paraclinical features that influence the risk of conversion to secondary progressive multiple sclerosis. Methods: Patients with adult-onset relapsing-remitting multiple sclerosis and at least four recorded disability scores were selected from MSBase, a global observational cohort. The risk of conversion to objectively defined secondary progressive multiple sclerosis was evaluated at multiple time points per patient using multivariable marginal Cox regression models. Sensitivity analyses were performed. Results: A total of 15,717 patients were included in the primary analysis. Older age (hazard ratio (HR) = 1.02, p < 0.001), longer disease duration (HR = 1.01, p = 0.038), a higher Expanded Disability Status Scale score (HR = 1.30, p < 0.001), more rapid disability trajectory (HR = 2.82, p < 0.001) and greater number of relapses in the previous year (HR = 1.07, p = 0.010) were independently associated with an increased risk of secondary progressive multiple sclerosis. Improving disability (HR = 0.62, p = 0.039) and disease-modifying therapy exposure (HR = 0.71, p = 0.007) were associated with a lower risk. Recent cerebral magnetic resonance imaging activity, evidence of spinal cord lesions and oligoclonal bands in the cerebrospinal fluid were not associated with the risk of conversion. Conclusion: Risk of secondary progressive multiple sclerosis increases with age, duration of illness and worsening disability and decreases with improving disability. Therapy may delay the onset of secondary progression. National Health and Medical Research Council of AustraliaNational Health and Medical Research Council of Australia [1083539, 1129189, 1140766]; BiogenBiogen; RocheRoche Holding; Bayer ScheringBayer AG; Sanofi Genzyme; Teva; MerckMerck & Company; NovartisNovartis The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was financially supported by National Health and Medical Research Council of Australia (project grants 1083539 and 1129189 and fellowship 1140766). The MSBase Foundation is a not-for-profit organisation that receives support from Merck, Biogen, Roche, Novartis, Bayer Schering, Sanofi Genzyme and Teva. The study was conducted separately and apart from the guidance of the sponsors.

Published
2020
Full Text
View/download PDF

15. Risk of relapse phenotype recurrence in multiple sclerosis

Author

Daniele Spitaleri, Joseph Herbert, Jeannette Lechner-Scott, Bhim Singhal, Tomas Kalincik, Carmen Adella Sirbu, Maria Edite Rio, Marc Girard, Celia Oreja-Guevara, Norbert Vella, Pierre Duquette, Raymond Hupperts, Francois Grand'Maison, Vincent Van Pesch, Alessandra Lugaresi, Maria Pia Amato, Raed Alroughani, Thor Petersen, Marcela Fiol, Gerardo Iuliano, Steve Vucic, Giorgio Giuliani, Ricardo Fernandez-Bolanos, Guillermo Izquierdo, Tatjana Petkovska-Boskova, Freek Verheul, Michael Barnett, Helmut Butzkueven, Mark Paine, Maria Laura Saladino, Jose Antonio Cabrera-Gomez, Erik van Munster, Maria Trojano, Roberto Bergamaschi, S. Flechter, Danny Liew, Orla Gray, Katherine Buzzard, Edgardo Cristiano, Cavit Boz, Mark Slee, Cameron Shaw, Aldo Savino, Vilija Jokubaitis, Csilla Rozsa, Fraser Moore, Pierre Grammond, John Parratt, MUMC+: MA Med Staf Spec Neurologie (9), Klinische Neurowetenschappen, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Kalincik T, Buzzard K, Jokubaitis V, Trojano M, Duquette P, Guillermo I, Girard M, Lugaresi A, Grammond P, Grand'maison F, Oreja-Guevara C, Boz C, Hupperts R, Petersen T, Giuliani G, Iuliano G, Lechner-Scott J, Barnett M, Bergamaschi R, Van Pesch V, Amato MP, van Munster E, Fernandez-Bolanos R, Verheul F, Fiol M, Cristiano E, Slee M, Rio ME, Spitaleri D, Alroughani R, Gray O, Saladino ML, Flechter S, Herbert J, Cabrera-Gomez JA, Vella N, Paine M, Shaw C, Moore F, Vucic S, Savino A, Singhal B, Petkovska-Boskova T, Parratt J, Sirbu CA, Rozsa C, Liew D, Butzkueven H, and on behalf of the MSBase Study Group

Subjects
Adult, Male, Risk, medicine.medical_specialty, phenotype, Disease, Logistic regression, MSBase, Multiple sclerosis, Disability Evaluation, Multiple Sclerosis, Relapsing-Remitting, Recurrence, Internal medicine, medicine, Humans, multiple sclerosis, relapse, symptom, prognosis, Aged, business.industry, Age Factors, presentation of neurological diseases, Middle Aged, medicine.disease, Phenotype, Natural history, Institutional repository, Neurology, Immunology, Disease Progression, Female, Observational study, prognosis, Neurology (clinical), business, Progressive disease
Abstract

Objectives: The aim was to analyse risk of relapse phenotype recurrence in multiple sclerosis and to characterise the effect of demographic and clinical features on this phenotype. Methods: Information about relapses was collected using MSBase, an international observational registry. Associations between relapse phenotypes and history of similar relapses or patient characteristics were tested with multivariable logistic regression models. Tendency of relapse phenotypes to recur sequentially was assessed with principal component analysis. Results: Among 14,969 eligible patients (89,949 patient-years), 49,279 phenotypically characterised relapses were recorded. Visual and brainstem relapses occurred more frequently in early disease and in younger patients. Sensory relapses were more frequent in early or non-progressive disease. Pyramidal, sphincter and cerebellar relapses were more common in older patients and in progressive disease. Women presented more often with sensory or visual symptoms. Men were more prone to pyramidal, brainstem and cerebellar relapses. Importantly, relapse phenotype was predicted by the phenotypes of previous relapses. (OR = 1.8–5, p = 10-14). Sensory, visual and brainstem relapses showed better recovery than other relapse phenotypes. Relapse severity increased and the ability to recover decreased with age or more advanced disease. Conclusion: Relapse phenotype was associated with demographic and clinical characteristics, with phenotypic recurrence significantly more common than expected by chance.

Published
2014
Full Text
View/download PDF

16. The effect of oral immunomodulatory therapy on treatment uptake and persistence in multiple sclerosis

Author

Warrender-Sparkes, Matthew, Spelman, Tim, Izquierdo, Guillermo, Trojano, Maria, Lugaresi, Alessandra, Grand'Maison, François, Havrdova, Eva, Horakova, Dana, Boz, Cavit, Oreja-Guevara, Celia, Alroughani, Raed, Iuliano, Gerardo, Duquette, Pierre, Girard, Marc, Terzi, Murat, Hupperts, Raymond, Grammond, Pierre, Petersen, Thor, Fernandez-Bolanos, Ricardo, Fiol, Marcela, Pucci, Eugenio, Lechner-Scott, Jeannette, Verheul, Freek, Cristiano, Edgardo, Van Pesch, Vincent, Petkovska-Boskova, Tatjana, Moore, Fraser, Kister, Ilya, Bergamaschi, Roberto, Saladino, Maria Laura, Slee, Mark, Barnett, Michael, Amato, Maria Pia, Shaw, Cameron, Shuey, Neil, Young, Carolyn, Gray, Orla, Kappos, Ludwig, Butzkueven, Helmut, Kalincik, Tomas, Jokubaitis, Vilija, MSBase study group, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Ondokuz Mayıs Üniversitesi, Warrender-Sparkes M, Spelman T, Izquierdo G, Trojano M, Lugaresi A, Grand'Maison F, Havrdova E, Horakova D, Boz C, Oreja-Guevara C, Alroughani R, Iuliano G, Duquette P, Girard M, Terzi M, Hupperts R, Grammond P, Petersen T, Fernandez-Bolaños R, Fiol M, Pucci E, Lechner-Scott J, Verheul F, Cristiano E, Van Pesch V, Petkovska-Boskova T, Moore F, Kister I, Bergamaschi R, Saladino Ml, Slee M, Barnett M, Amato Mp, Shaw C, Shuey N, Young C, Gray O, Kappos L, Butzkueven H, Kalincik T, Jokubaitis V, and Msbase study group.

Subjects
Oncology, Male, Time Factors, Administration, Oral, Kaplan-Meier Estimate, Pharmacology, Persistence (computer science), 0302 clinical medicine, Natalizumab, Risk Factors, 030212 general & internal medicine, Prospective Studies, Registries, Prospective cohort study, Drug Substitution, Research Support, Non-U.S. Gov't, Middle Aged, Fingolimod, disease-modifying therapy, Treatment Outcome, Neurology, Cohort, Female, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, MSBase, Medication Adherence, Multiple sclerosis, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Fingolimod Hydrochloride, medicine, Journal Article, Humans, Multiple sclerosi, fingolimod, Aged, Proportional Hazards Models, business.industry, medicine.disease, Medication Persistence, Multivariate Analysis, Neurology (clinical), business, 030217 neurology & neurosurgery, medication persistence, Demyelinating Diseases
Abstract

Lugaresi, Alessandra/0000-0003-2902-5589; Horakova, Dana/0000-0003-1915-0036; amato, Maria Pia/0000-0003-3325-3760; Havrdova, Eva Kubala/0000-0002-9543-4359; Slee, Mark/0000-0003-4323-2453; Jokubaitis, Vilija G./0000-0002-3942-4340; Oreja-Guevara, Celia/0000-0002-9221-5716; Petersen, Thor/0000-0001-5633-2600; pucci, eugenio/0000-0001-7606-7330; , Carolyn/0000-0001-6971-8203; van Pesch, Vincent/0000-0003-2885-9004; Butzkueven, Helmut/0000-0003-3940-8727; Trojano, Maria/0000-0002-6329-8946; Young, Carolyn/0000-0003-1745-7720; Kalincik, Tomas/0000-0003-3778-1376; Kister, Ilya/0000-0003-3549-949X WOS: 000372890900008 PubMed: 26199347 Objective: We aimed to analyse the effect of the introduction of fingolimod, the first oral disease-modifying therapy, on treatment utilisation and persistence in an international cohort of patients with multiple sclerosis (MS). Methods: MSBASIS, a prospective, observational sub-study of the MSBase registry, collects demographic, clinical and paraclinical data on patients followed from MS onset (n=4718). We conducted a multivariable conditional risk set survival analysis to identify predictors of treatment discontinuation, and to assess if the introduction of fingolimod has altered treatment persistence. Results: A total of 2640 patients commenced immunomodulatory therapy. Following the introduction of fingolimod, patients were more likely to discontinue all other treatments (hazard ratio 1.64, p

Published
2016
Full Text
View/download PDF

17. Male Sex Is Independently Associated with Faster Disability Accumulation in Relapse-Onset MS but Not in Primary Progressive MS

Author

Karen Ann Ribbons, Patrick McElduff, Cavit Boz, Maria Trojano, Guillermo Izquierdo, Pierre Duquette, Marc Girard, Francois Grand'Maison, Raymond Hupperts, Pierre Grammond, Celia Oreja-Guevara, Thor Petersen, Roberto Bergamaschi, Giorgio Giuliani, Michael Barnett, Vincent van Pesch, Maria-Pia Amato, Gerardo Iuliano, Marcela Fiol, Mark Slee, Freek Verheul, Edgardo Cristiano, Ricardo Fernandez-Bolanos, Maria-Laura Saladino, Maria Edite Rio, Jose Cabrera-Gomez, Helmut Butzkueven, Erik van Munster, Leontien Den Braber-Moerland, Daniele La Spitaleri, Alessandra Lugaresi, Vahid Shaygannejad, Orla Gray, Norma Deri, Raed Alroughani, Jeannette Lechner-Scott, Ribbons Ka, Mcelduff P, Boz C, Trojano M, Izquierdo G, Duquette P, Girard M, Grand'Maison F, Hupperts R, Grammond P, Oreja-Guevara C, Petersen T, Bergamaschi R, Giuliani G, Barnett M, van Pesch V, Amato Mp, Iuliano G, Fiol M, Slee M, Verheul F, Cristiano E, Fernandez-Bolanos R, Saladino Ml, Rio Me, Cabrera-Gomez J, Butzkueven H, van Munster E, Den Braber-Moerland L, La Spitaleri D, Lugaresi A, Shaygannejad V, Gray O, Deri N, Alroughani R, Lechner-Scott J, MUMC+: MA Med Staf Spec Neurologie (9), Klinische Neurowetenschappen, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, and UCL - (SLuc) Service de neurologie

Subjects
Gerontology, Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Databases, Factual, Immunologic Factors, lcsh:Medicine, Kaplan-Meier Estimate, Severity of Illness Index, Primary progressive, Cohort Studies, Disability Evaluation, Sex Factors, Sex factors, Recurrence, Internal medicine, Severity of illness, medicine, Journal Article, Humans, Registries, lcsh:Science, Aged, Proportional Hazards Models, Multidisciplinary, Proportional hazards model, business.industry, Multiple sclerosis, Research Support, Non-U.S. Gov't, Disease progression, lcsh:R, Faster Disability Accumulation, Relapse-Onset , Primary Progressive MS, Middle Aged, medicine.disease, Disease Progression, lcsh:Q, Female, business, male, female, multiple sclerosis, prognosis, Cohort study, Research Article
Abstract

Background Multiple Sclerosisismore common inwomenthanmenandfemales have morerelapsesthanmen. Inalargeinternationalcohortwehave evaluatedthe effectofgenderondisabilityaccumulationanddiseaseprogressiontodetermineifmale MSpatientshaveaworse clini-caloutcome thanfemales. Methods Usingthe MSBase Registry, data from15,826MSpatients from 25countrieswasanalysed.Changesin theseverityofMS(EDSS)were comparedbetweensexesusingarepeatedmeasuresanalysisin generalisedlinearmixed models.Kaplan-Meier analysis wasusedto PLOSONE|DOI:10.1371/journal.pone.0122686 June5,2015 1/11OPENACCESSCitation:RibbonsKA,McElduffP,BozC,TrojanoM,IzquierdoG,DuquetteP,etal.(2015)MaleSexIsIndependentlyAssociatedwithFasterDisabilityAccumulationinRelapse-OnsetMSbutNotinPrimaryProgressiveMS.PLoSONE10(6):e0122686.doi:10.1371/journal.pone.0122686AcademicEditor:OrhanAktas,UniversityofDusseldorf,GERMANYReceived:August26,2014Accepted:February26,2015Published:June5,2015Copyright:©2015Ribbonsetal.ThisisanopenaccessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.DataAvailabilityStatement:Allrelevantdataareavailablefromco-authorsuponrequest.Contactinformationforeachco-authorisinSupportingInformation.Funding:MerckSeronosupportsiMEDwhichisthesoftwareprogramusedbyMSBASEfordataacquisitionateachcollaboratingcentreanddoesnotimpactonthestudiesderivedfromdatacollectedbythisprogram.Thefundershadnoroleinstudydesign,datacollectionandanalysis,decisiontopublish,orpreparationofthemanuscript.

Published
2015
Full Text
View/download PDF

18. Comparative effectiveness of glatiramer acetate and interferon beta formulations in relapsing-remitting multiple sclerosis

Author

Ricardo Fernandez-Bolanos, Orla Gray, Mark Paine, Helmut Butzkueven, Eva Havrdova, Guillermo Izquierdo, Daniele Spitaleri, Michael Barnett, Jose Antonio Cabrera-Gomez, Pierre Grammond, Maria Trojano, Alessandra Lugaresi, Maria Laura Saladino, Edgardo Cristiano, Jeannette Lechner-Scott, Vilija Jokubaitis, Eugenio Pucci, Maria Pia Amato, Celia Oreja-Guevara, Pierre Duquette, Fraser Moore, Raymond Hupperts, Mark Slee, Shlomo Flechter, Dana Horakova, Francois Grand'Maison, Gerardo Iuliano, Tim Spelman, Roberto Bergamaschi, Cavit Boz, Vincent Van Pesch, Tomas Kalincik, Marc Girard, Freek Verheul, MUMC+: MA Med Staf Spec Neurologie (9), Klinische Neurowetenschappen, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Kalincik T, Jokubaitis V, Izquierdo G, Duquette P, Girard M, Grammond P, Lugaresi A, Oreja-Guevara C, Bergamaschi R, Hupperts R, Grand'Maison F, Pucci E, Van Pesch V, Boz C, Iuliano G, Fernandez-Bolanos R, Flechter S, Spitaleri D, Cristiano E, Verheul F, Lechner-Scott J, Amato MP, Cabrera-Gomez JA, Saladino ML, Slee M, Moore F, Gray O, Paine M, Barnett M, Havrdova E, Horakova D, Spelman T, Trojano M, Butzkueven H, and On behalf of the MSBase Study Group

Subjects
medicine.medical_specialty, relapses, media_common.quotation_subject, treatment outcomes, Multiple sclerosis, patient registry, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, medicine, Humans, Immunologic Factors, Multiple sclerosi, Registries, Glatiramer acetate, Relapse, propensity score, media_common, real-world date, Selection bias, medicine.diagnostic_test, Proportional hazards model, business.industry, Incidence (epidemiology), Magnetic resonance imaging, Glatiramer Acetate, Interferon-beta, medicine.disease, Surgery, Institutional repository, Treatment Outcome, Neurology, disability, Propensity score matching, Neurology (clinical), business, medicine.drug
Abstract

Background: The results of head-to-head comparisons of injectable immunomodulators (interferon β, glatiramer acetate) have been inconclusive and a comprehensive analysis of their effectiveness is needed. Objective: We aimed to compare, in a real-world setting, relapse and disability outcomes among patients with multiple sclerosis (MS) treated with injectable immunomodulators. Methods: Pairwise analysis of the international MSBase registry data was conducted using propensity-score matching. The four injectable immunomodulators were compared in six head-to-head analyses of relapse and disability outcomes using paired mixed models or frailty proportional hazards models adjusted for magnetic resonance imaging variables. Sensitivity and power analyses were conducted. Results: Of the 3326 included patients, 345–1199 patients per therapy were matched (median pairwise-censored follow-up was 3.7 years). Propensity matching eliminated >95% of the identified indication bias. Slightly lower relapse incidence was found among patients treated with glatiramer acetate or subcutaneous interferon β-1a relative to intramuscular interferon β-1a and interferon β-1b ( p≤0.001). No differences in 12-month confirmed progression of disability were observed. Conclusion: Small but statistically significant differences in relapse outcomes exist among the injectable immunomodulators. MSBase is sufficiently powered to identify these differences and reflects practice in tertiary MS centres. While the present study controlled indication, selection and attrition bias, centre-dependent variance in data quality was likely.

Published
2014

19. Seasonal variation of relapse rate in multiple sclerosis is latitude dependent

Author

Spelman, Tim, Gray, Orla, Trojano, Maria, Petersen, Thor, Izquierdo, Guillermo, Lugaresi, Alessandra, Hupperts, Raymond, Bergamaschi, Roberto, Duquette, Pierre, Grammond, Pierre, Giuliani, Giorgio, Boz, Cavit, Verheul, Freek, Oreja-Guevara, Celia, Barnett, Michael, Grand'Maison, Francois, Edite Rio, Maria, Lechner-Scott, Jeannette, Van Pesch, Vincent, Fernandez Bolanos, Ricardo, Flechter, Shlomo, Den Braber-Moerland, Leontien, Iuliano, Gerardo, Amato, Maria Pia, Slee, Mark, Cristiano, Edgardo, Saladino, Maria Laura, Paine, Mark, Vella, Norbert, Kasa, Krisztian, Deri, Norma, Herbert, Joseph, Moore, Fraser, Petkovska-Boskova, Tatjana, Alroughani, Raed, Savino, Aldo, Shaw, Cameron, Vucic, Steve, Santiago, Vetere, Bacile, Elizabeth Alejandra, Skromne, Eli, Poehlau, Dieter, Cabrera-Gomez, Jose Antonio, Lucas, Robyn, Butzkueven, Helmut, Spelman T, Gray O, Trojano M, Petersen T, Izquierdo G, Lugaresi A, Hupperts R, Bergamaschi R, Duquette P, Grammond P, Giuliani G, Boz C, Verheul F, Oreja-Guevara C, Barnett M, Grand'Maison F, Edite Rio M, Lechner-Scott J, Van Pesch V, Fernandez Bolanos R, Flechter S, Den Braber-Moerland L, Iuliano G, Amato MP, Slee M, Cristiano E, Saladino ML, Paine M, Vella N, Kasa K, Deri N, Herbert J, Moore F, Petkovska-Boskova T, Alroughani R, Savino A, Shaw C, Vucic S, Santiago V, Bacile EA, Skromne E, Poehlau D, Cabrera-Gomez JA, Lucas R, Butzkueven H, MUMC+: MA Med Staf Spec Neurologie (9), Klinische Neurowetenschappen, and RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience

Subjects
Adult, Male, Internationality, Databases, Factual, Ultraviolet Rays, Young Adult, Multiple Sclerosis, Relapsing-Remitting, Recurrence, Sunlight, Humans, Female, seasonal, variation, multiple sclerosis,relapse, Longitudinal Studies, Prospective Studies, Registries, Seasons
Abstract

OBJECTIVE: Previous studies assessing seasonal variation of relapse onset in multiple sclerosis have had conflicting results. Small relapse numbers, differing diagnostic criteria, and single region studies limit the generalizability of prior results. The aim of this study was to determine whether there is a temporal variation in onset of relapses in both hemispheres and to determine whether seasonal peak relapse probability varies with latitude.METHODS: The international MSBase Registry was utilized to analyze seasonal relapse onset distribution by hemisphere and latitudinal location. All analyses were weighted for the patient number contributed by each center. A sine regression model was used to model relapse onset and ultraviolet radiation (UVR) seasonality. Linear regression was used to investigate associations of latitude and lag between UVR trough and subsequent relapse peak.RESULTS: A total of 32,762 relapses from 9,811 patients across 30 countries were analyzed. Relapse onset followed an annual cyclical sinusoidal pattern with peaks in early spring and troughs in autumn in both hemispheres. Every 10° of latitude away from the equator was associated with a mean decrease in UVR trough to subsequent relapse peak lag of 28.5 days (95% confidence interval = 3.29-53.71, p = 0.028).INTERPRETATION: We demonstrate for the first time that there is a latitude-dependent relationship between seasonal UVR trough and relapse onset probability peak independent of location-specific UVR levels, with more distal latitude associated with shorter gaps. We confirm prior meta-analyses showing a strong seasonal relapse onset probability variation in the northern hemisphere, and extend this observation to the southern hemisphere. Ann Neurol 2014;76:880-890.

Published
2014
Full Text
View/download PDF

20. Persistence on therapy and propensity matched outcome comparison of two subcutaneous interferon beta 1a dosages for multiple sclerosis

Author

Tobias Derfuss, Tomas Kalincik, Timothy Spelman, Maria Trojano, Pierre Duquette, Guillermo Izquierdo, Pierre Grammond, LUGARESI, ALESSANDRA, Raymond Hupperts, Edgardo Cristiano, Vincent Van Pesch, Francois Grand’Maison, Daniele La Spitaleri, Maria Edite Rio, Sholmo Flechter, Celia Oreja Guevara, Giorgio Giuliani, Aldo Savino, Maria Pia Amato, Thor Petersen, Ricardo Fernandez Bolanos, Roberto Bergamaschi, Gerardo Iuliano, Cavit Boz, Jeannette Lechner Scott, Norma Deri, Orla Gray, Freek Verheul, Marcela Fiol, Michael Barnett, Erik van Munster, Vetere Santiago, Fraser Moore, Mark Slee, Maria Laura Saladino, Raed Alroughani, Cameron Shaw, Krisztian Kasa, Tatjana Petkovska Boskova, Leontien den Braber Moerland, Joab Chapman, Eli Skromne, Joseph Herbert, Dieter Poehlau, Merrilee Needham, Elizabeth Alejandra Bacile Bacile, Walter Oleschko Arruda, Mark Paine, Bhim Singhal, Steve Vucic, Jose Antonio Cabrera Gomez, Helmut Butzkueven, MSBase Study Group, Klinische Neurowetenschappen, RS: MHeNs School for Mental Health and Neuroscience, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, Tobias Derfu, Tomas Kalincik, Timothy Spelman, Maria Trojano, Pierre Duquette, Guillermo Izquierdo, Pierre Grammond, Alessandra Lugaresi, Raymond Huppert, Edgardo Cristiano, Vincent Van Pesch, Francois Grand’Maison, Daniele La Spitaleri, Maria Edite Rio, Sholmo Flechter, Celia Oreja-Guevara, Giorgio Giuliani, Aldo Savino, Maria Pia Amato, Thor Petersen, Ricardo Fernandez-Bolano, Roberto Bergamaschi, Gerardo Iuliano, Cavit Boz, Jeannette Lechner-Scott, Norma Deri, Orla Gray, Freek Verheul, Marcela Fiol, Michael Barnett, Erik van Munster, Vetere Santiago, Fraser Moore, Mark Slee, Maria Laura Saladino, Raed Alroughani, Cameron Shaw, Krisztian Kasa, Tatjana Petkovska-Boskova, Leontien den Braber-Moerland, Joab Chapman, Eli Skromne, Joseph Herbert, Dieter Poehlau, Merrilee Needham, Elizabeth Alejandra Bacile Bacile, Walter Oleschko Arruda, Mark Paine, Bhim Singhal, Steve Vucic, Jose Antonio Cabrera-Gomez, Helmut Butzkueven, MSBase Study Group, The MSBase Study Group, [Karkincic,T, and Butzkueven,H] Departments of Medicine and Neurology, University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia. [Spelman,T] Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia. [Trojano,M] Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy. [Duquette,P] Hòpital Notre Dame, Montreal, Canada. [Izquierdo,G] Hospital Universitario Virgen Macarena, Sevilla, Spain. [Grammond,P] Hotel-Dieu de Levis, Quebec, Canada. [Lugaresi,A] MS Center, Department of Neuroscience and Imaging, University ‘G. d’Annunzio’, Chieti, Italy. [Hupperts,R] Maaslandziekenhuis, Sittard, The Netherlands. [Cristiano,E] Hospital Italiano, Buenos Aires, Argentina. [Van Pesch,V] Cliniques Universitaires Saint-Luc, Brussels, Belgium. [Grand´Maison,F ]Neuro Rive-Sud, Hòpital Charles LeMoyne, Quebec, Canada. [La Spitaleri,D] AORN San Giuseppe Moscati, Avellino, Italy. [Rio,ME] Hospital S. Joao, Porto, Portugal. [Flechter,S] Assaf Harofeh Medical Center, Beer-Yaakov, Israel. [Oreja-Guevera,C] University Hospital San Carlos, IdISSC, Madrid, Spain. [Giuliani,G] Ospedale di Macerata, Macerata, Italy. [Savino,A] Consultorio Privado, Buenos Aires, Argentina. [Amato,MP] Department NEUROFARBA, Section of Neurology, University of Florence, Florence, Italy. [Petersen,T] Kommunehospitalet, Aarhus C, Denmark. [Fernandez-Bolanos,R] Hospital Universitario Virgen de Valme, Seville, Spain. [Bergamaschi,R] Neurological Institute IRCCS Mondino, Pavia, Italy. [Iuliano,G] Ospedali Riuniti di Salerno, Salerno, Italy. [Boz,C] Karadeniz Technical University, Trabzon, Turkey. [Lechner-Scott,J] John Hunter Hospital, Newcastle, Australia. [Deri,N] Hospital Fernandez, Buenos Aires, Argentina.[Gray,O] Craigavon Area Hospital, Portadown, United Kingdom. [Verheul,F] Groen Hart Ziekenhuis, Gouda, The Netherlands. [Fiol,M] FLENI, Buenos Aires, Argentina. [Barnett,M] Brain and Mind Research Institute, Sydney, Australia. [van Munster,E] Jeroen Bosch Ziekenhuis, ‘s-Hertogenbosch, The Netherlands. [Santiago,V]HIGA Gral, San Martin La Plata, Argentina. [Moore,F] Jewish General Hospital, McGill University, Montreal, Canada. [Slee,M] Flinders University and Medical Centre, Adelaide, Australia. [Saladino,ML] INEBA, Buenos Aires, Argentina. [Alroughani,R] Amiri Hospital, Kuwait City, Kuwait. [Shaw,C] Geelong Hospital, Geelong, Australia. [Kasa,K] Jahn Ferenc Teaching Hospital, Budapest, Hungary. [Petkovska-Boskova,T] Clinic of Neurology Clinical Center, Skopje, Macedonia. [den Braber-Moerland,L] Francicus Ziekenhuis, Roosendaal, The Netherlands. [Chapman,J] Sheba Medical Center, Tel Hashomer, Israel. [Skromne,E] Hospital Angeles Mexico City, Lomas, Mexico. [Herbert,J] New York University Hospital for Joint Diseases, New York, New York, United States of America. [Poehlau,D] Multiple Sclerosis Centre Kamillus-Klinik, Asbach, Germany. [Needham,M] Royal North Shore Hospital, Sydney, Australi. [Bacile Bacile,EA] Instituto de Neurociencias Cordoba, Cordoba, Argentin. [Arruda,WO] Hospital Ecoville, Curitiba, Brazil. [Paine, M] St Vincent’s Hospital, Melbourne, Australia. [Sighal,B] Bombay Hospital Institute of Medical Sciences, Mumbai, India. [Vucic,S] Westmead Hospital, Sydney, Australia. [Cabrera-Gomez,JA] Centro Internacional de Restauracion Neurologica, Havana, Cuba. [Butzkueven,H] Department of Neurology, Box Hill Hospital and Monash University, Melbourne, Australia.

Subjects
Male, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Patient Care::Withholding Treatment [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Magnetic Resonance Imaging [Medical Subject Headings], Kaplan-Meier Estimate, law.invention, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Randomized controlled trial, law, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Likelihood Functions [Medical Subject Headings], Longitudinal Studies, Non-U.S. Gov't, Espectroscopía de resonancia magnética, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Administration Schedule [Medical Subject Headings], Likelihood Functions, Multidisciplinary, Adulto, Subcutaneous, Research Support, Non-U.S. Gov't, Statistics, Drug Information, Magnetic Resonance Imaging, Clinical Trial, Funciones de verosimilitud, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Reproducibility of Results [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Drug Administration Routes::Injections::Injections, Subcutaneous [Medical Subject Headings], Treatment Outcome, Relación dosis-respuesta a droga, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines::Interferons::Interferon Type I::Interferon-beta [Medical Subject Headings], Neurology, Observational Studies, Medicine, Female, Drug, Interferon beta-1a, Research Article, medicine.drug, Adult, Drugs and Devices, medicine.medical_specialty, Multiple Sclerosis, Clinical Research Design, Science, Injections, Subcutaneous, Cumplimiento y adherencia al tratamiento, Reproducibilidad de los resultados, Check Tags::Male [Medical Subject Headings], Biostatistics, Diseases::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [Medical Subject Headings], Research Support, Drug Administration Schedule, Autoimmune Diseases, Injections, Medication Adherence, Dose-Response Relationship, Adverse Reactions, Internal medicine, Covariate, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], medicine, Journal Article, Humans, Comparative Study, Statistical Methods, Adverse effect, Propensity Score, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings], Demography, Interferón beta, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Survival Analysis::Kaplan-Meier Estimate [Medical Subject Headings], Dose-Response Relationship, Drug, business.industry, Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Dose-Response Relationship, Drug [Medical Subject Headings], Multiple sclerosis, Reproducibility of Results, Inyecciones subcutáneas, multiple sclerosis drug therapy, Interferon-beta, medicine.disease, Disciplines and Occupations::Social Sciences::Demography [Medical Subject Headings], Demyelinating Disorders, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Propensity Score [Medical Subject Headings], Clinical trial, Check Tags::Female [Medical Subject Headings], Withholding Treatment, Esclerosis múltiple, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Health Behavior::Patient Compliance::Medication Adherence [Medical Subject Headings], Propensity score matching, Clinical Immunology, Observational study, Resultado del tratamiento, business, Privación del tratamiento, Mathematics
Abstract

Clinical Trial; Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; OBJECTIVES To compare treatment persistence between two dosages of interferon β-1a in a large observational multiple sclerosis registry and assess disease outcomes of first line MS treatment at these dosages using propensity scoring to adjust for baseline imbalance in disease characteristics. METHODS Treatment discontinuations were evaluated in all patients within the MSBase registry who commenced interferon β-1a SC thrice weekly (n = 4678). Furthermore, we assessed 2-year clinical outcomes in 1220 patients treated with interferon β-1a in either dosage (22 µg or 44 µg) as their first disease modifying agent, matched on propensity score calculated from pre-treatment demographic and clinical variables. A subgroup analysis was performed on 456 matched patients who also had baseline MRI variables recorded. RESULTS Overall, 4054 treatment discontinuations were recorded in 3059 patients. The patients receiving the lower interferon dosage were more likely to discontinue treatment than those with the higher dosage (25% vs. 20% annual probability of discontinuation, respectively). This was seen in discontinuations with reasons recorded as "lack of efficacy" (3.3% vs. 1.7%), "scheduled stop" (2.2% vs. 1.3%) or without the reason recorded (16.7% vs. 13.3% annual discontinuation rate, 22 µg vs. 44 µg dosage, respectively). Propensity score was determined by treating centre and disability (score without MRI parameters) or centre, sex and number of contrast-enhancing lesions (score including MRI parameters). No differences in clinical outcomes at two years (relapse rate, time relapse-free and disability) were observed between the matched patients treated with either of the interferon dosages. CONCLUSIONS Treatment discontinuations were more common in interferon β-1a 22 µg SC thrice weekly. However, 2-year clinical outcomes did not differ between patients receiving the different dosages, thus replicating in a registry dataset derived from "real-world" database the results of the pivotal randomised trial. Propensity score matching effectively minimised baseline covariate imbalance between two directly compared sub-populations from a large observational registry. This study was funded by MSBase Foundation, a not-for-profit organisation. The MSBase Foundation receives financial support from Merck Serono, Biogen Idec, Novartis Pharma, Bayer Schering and Sanofi Aventis. The study was also funded by Multiple Sclerosis Research Australia and MSAngels. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Yes

Published
2013
Full Text
View/download PDF

21. 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

Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results