518 results on '"Laureys G"'
Search Results
2. Off-label drug use in paediatric haemato-oncology patients: financial implications and proposed solutions for Belgian patients
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Bauters, T., Heenen, D., Norga, K., Van Damme, A., Uyttebroeck, A., and Laureys, G.
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- 2021
- Full Text
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3. Machine-learning-based prediction of disability progression in multiple sclerosis: An observational, international, multi-center study
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McGinnis, RS, De Brouwer, E, Becker, T, Werthen-Brabants, L, Dewulf, P, Iliadis, D, Dekeyser, C, Laureys, G, Van Wijmeersch, B, Popescu, V, Dhaene, T, Deschrijver, D, Waegeman, W, De Baets, B, Stock, M, Horakova, D, Patti, F, Izquierdo, G, Eichau, S, Girard, M, Prat, A, Lugaresi, A, Grammond, P, Kalincik, T, Alroughani, R, Grand'Maison, F, Skibina, O, Terzi, M, Lechner-Scott, J, Gerlach, O, Khoury, SJ, Cartechini, E, Van Pesch, V, Sà, MJ, Weinstock-Guttman, B, Blanco, Y, Ampapa, R, Spitaleri, D, Solaro, C, Maimone, D, Soysal, A, Iuliano, G, Gouider, R, Castillo-Triviño, T, Sánchez-Menoyo, JL, van der Walt, A, Oh, J, Aguera-Morales, E, Altintas, A, Al-Asmi, A, de Gans, K, Fragoso, Y, Csepany, T, Hodgkinson, S, Deri, N, Al-Harbi, T, Taylor, B, Gray, O, Lalive, P, Rozsa, C, McGuigan, C, Kermode, A, Sempere, AP, Mihaela, S, Simo, M, Hardy, T, Decoo, D, Hughes, S, Grigoriadis, N, Sas, A, Vella, N, Moreau, Y, Peeters, L, McGinnis, RS, De Brouwer, E, Becker, T, Werthen-Brabants, L, Dewulf, P, Iliadis, D, Dekeyser, C, Laureys, G, Van Wijmeersch, B, Popescu, V, Dhaene, T, Deschrijver, D, Waegeman, W, De Baets, B, Stock, M, Horakova, D, Patti, F, Izquierdo, G, Eichau, S, Girard, M, Prat, A, Lugaresi, A, Grammond, P, Kalincik, T, Alroughani, R, Grand'Maison, F, Skibina, O, Terzi, M, Lechner-Scott, J, Gerlach, O, Khoury, SJ, Cartechini, E, Van Pesch, V, Sà, MJ, Weinstock-Guttman, B, Blanco, Y, Ampapa, R, Spitaleri, D, Solaro, C, Maimone, D, Soysal, A, Iuliano, G, Gouider, R, Castillo-Triviño, T, Sánchez-Menoyo, JL, van der Walt, A, Oh, J, Aguera-Morales, E, Altintas, A, Al-Asmi, A, de Gans, K, Fragoso, Y, Csepany, T, Hodgkinson, S, Deri, N, Al-Harbi, T, Taylor, B, Gray, O, Lalive, P, Rozsa, C, McGuigan, C, Kermode, A, Sempere, AP, Mihaela, S, Simo, M, Hardy, T, Decoo, D, Hughes, S, Grigoriadis, N, Sas, A, Vella, N, Moreau, Y, and Peeters, L
- Abstract
BACKGROUND: Disability progression is a key milestone in the disease evolution of people with multiple sclerosis (PwMS). Prediction models of the probability of disability progression have not yet reached the level of trust needed to be adopted in the clinic. A common benchmark to assess model development in multiple sclerosis is also currently lacking. METHODS: Data of adult PwMS with a follow-up of at least three years from 146 MS centers, spread over 40 countries and collected by the MSBase consortium was used. With basic inclusion criteria for quality requirements, it represents a total of 15, 240 PwMS. External validation was performed and repeated five times to assess the significance of the results. Transparent Reporting for Individual Prognosis Or Diagnosis (TRIPOD) guidelines were followed. Confirmed disability progression after two years was predicted, with a confirmation window of six months. Only routinely collected variables were used such as the expanded disability status scale, treatment, relapse information, and MS course. To learn the probability of disability progression, state-of-the-art machine learning models were investigated. The discrimination performance of the models is evaluated with the area under the receiver operator curve (ROC-AUC) and under the precision recall curve (AUC-PR), and their calibration via the Brier score and the expected calibration error. All our preprocessing and model code are available at https://gitlab.com/edebrouwer/ms_benchmark, making this task an ideal benchmark for predicting disability progression in MS. FINDINGS: Machine learning models achieved a ROC-AUC of 0⋅71 ± 0⋅01, an AUC-PR of 0⋅26 ± 0⋅02, a Brier score of 0⋅1 ± 0⋅01 and an expected calibration error of 0⋅07 ± 0⋅04. The history of disability progression was identified as being more predictive for future disability progression than the treatment or relapses history. CONCLUSIONS: Good discrimination and calibration performance on an external validation s
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- 2024
4. Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom
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Spelman, T, primary, Herring, WL, additional, Acosta, C, additional, Hyde, R, additional, Jokubaitis, VG, additional, Pucci, E, additional, Lugaresi, A, additional, Laureys, G, additional, Havrdova, EK, additional, Horakova, D, additional, Izquierdo, G, additional, Eichau, S, additional, Ozakbas, S, additional, Alroughani, R, additional, Kalincik, T, additional, Duquette, P, additional, Girard, M, additional, Petersen, T, additional, Patti, F, additional, Csepany, T, additional, Granella, F, additional, Grand’Maison, F, additional, Ferraro, D, additional, Karabudak, R, additional, Jose Sa, M, additional, Trojano, M, additional, van Pesch, V, additional, Van Wijmeersch, B, additional, Cartechini, E, additional, McCombe, P, additional, Gerlach, O, additional, Spitaleri, D, additional, Rozsa, C, additional, Hodgkinson, S, additional, Bergamaschi, R, additional, Gouider, R, additional, Soysal, A, additional, Castillo-Triviño, T, additional, Prevost, J, additional, Garber, J, additional, de Gans, K, additional, Ampapa, R, additional, Simo, M, additional, Sanchez-Menoyo, JL, additional, Iuliano, G, additional, Sas, A, additional, van der Walt, A, additional, John, N, additional, Gray, O, additional, Hughes, S, additional, De Luca, G, additional, Onofrj, M, additional, Buzzard, K, additional, Skibina, O, additional, Terzi, M, additional, Slee, M, additional, Solaro, C, additional, Oreja-Guevara, C, additional, Ramo-Tello, C, additional, Fragoso, Y, additional, Shaygannejad, V, additional, Moore, F, additional, Rajda, C, additional, Aguera Morales, E, additional, and Butzkueven, H, additional
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- 2023
- Full Text
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5. Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom.
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Spelman, T., Herring, W. L., Acosta, C., Hyde, R., Jokubaitis, V. G., Pucci, E., Lugaresi, A., Laureys, G., Havrdova, E. K., Horakova, D., Izquierdo, G., Eichau, S., Ozakbas, S., Alroughani, R., Kalincik, T., Duquette, P., Girard, M., Petersen, T., Patti, F., and Csepany, T.
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GLATIRAMER acetate ,DIMETHYL fumarate ,PROPENSITY score matching ,FINGOLIMOD ,MEDICAL registries - Abstract
Aim: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). Methods: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month–confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. Results: In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57–0.73) or BRACETD (RR = 0.46; 95% CI, 0.42–0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01–1.55) and BRACETD (HR = 1.46; 95% CI, 1.16–1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65–0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91–1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. Conclusions: This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS. PLAIN LANGUAGE SUMMARY: There are several medications used to treat people with relapsing remitting multiple sclerosis, such as interferon-based therapies (Betaferon/Betaseron (US), Rebif, Avonex, Extavia), glatiramer acetate (Copaxone), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera), collectively named BRACETD. Other treatments for multiple sclerosis (MS) have a narrower use, such as natalizumab (Tysabri) or fingolimod (Gilenya), among others. This study objective was to assess how well natalizumab and fingolimod helped treating MS (clinical effectiveness) and subsequently estimate what the cost of these treatments is in comparison to the benefit they bring to people with rapidly evolving severe MS that use them in the United Kingdom (UK) (cost-effectiveness). We used an international disease registry (MSBase), which collects clinical data from people with MS in various centers around the world to compare the effectiveness of natalizumab, fingolimod and BRACETD treatments. We used a technique called propensity score matching to obtain results from comparable patient groups. People treated with natalizumab had better disease control, namely with fewer relapses and higher improvement on their disability level, than patients on fingolimod or BRACETD. Conversely, there were no differences between each group of people on a measure called disability worsening. Based on these clinical results, we built an economic model that simulates the lifetime costs and consequences of treating people with MS with natalizumab in comparison with fingolimod. We found that using natalizumab was less costly and was more effective compared to using fingolimod in UK patients. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
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6. Comparison Between Dimethyl Fumarate, Fingolimod, and Ocrelizumab After Natalizumab Cessation
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Zhu, C, Kalincik, T, Horakova, D, Zhou, Z, Buzzard, K, Skibina, O, Alroughani, R, Izquierdo, G, Eichau, S, Kuhle, J, Patti, F, Grand'Maison, F, Hodgkinson, S, Grammond, P, Lechner-Scott, J, Butler, E, Prat, A, Girard, M, Duquette, P, Macdonell, RAL, Weinstock-Guttman, B, Ozakbas, S, Slee, M, Sa, MJ, Van Pesch, V, Barnett, M, Van Wijmeersch, B, Gerlach, O, Prevost, J, Terzi, M, Boz, C, Laureys, G, Van Hijfte, L, Kermode, AG, Garber, J, Yamout, B, Khoury, SJ, Merlo, D, Monif, M, Jokubaitis, V, van der Walt, A, Butzkueven, H, MSBase, SG, Zhu, C, Kalincik, T, Horakova, D, Zhou, Z, Buzzard, K, Skibina, O, Alroughani, R, Izquierdo, G, Eichau, S, Kuhle, J, Patti, F, Grand'Maison, F, Hodgkinson, S, Grammond, P, Lechner-Scott, J, Butler, E, Prat, A, Girard, M, Duquette, P, Macdonell, RAL, Weinstock-Guttman, B, Ozakbas, S, Slee, M, Sa, MJ, Van Pesch, V, Barnett, M, Van Wijmeersch, B, Gerlach, O, Prevost, J, Terzi, M, Boz, C, Laureys, G, Van Hijfte, L, Kermode, AG, Garber, J, Yamout, B, Khoury, SJ, Merlo, D, Monif, M, Jokubaitis, V, van der Walt, A, Butzkueven, H, and MSBase, SG
- Abstract
IMPORTANCE: Natalizumab cessation is associated with a risk of rebound disease activity. It is important to identify the optimal switch disease-modifying therapy strategy after natalizumab to limit the risk of severe relapses. OBJECTIVES: To compare the effectiveness and persistence of dimethyl fumarate, fingolimod, and ocrelizumab among patients with relapsing-remitting multiple sclerosis (RRMS) who discontinued natalizumab. DESIGN, SETTING, AND PARTICIPANTS: In this observational cohort study, patient data were collected from the MSBase registry between June 15, 2010, and July 6, 2021. The median follow-up was 2.7 years. This was a multicenter study that included patients with RRMS who had used natalizumab for 6 months or longer and then were switched to dimethyl fumarate, fingolimod, or ocrelizumab within 3 months after natalizumab discontinuation. Patients without baseline data were excluded from the analysis. Data were analyzed from May 24, 2022, to January 9, 2023. EXPOSURES: Dimethyl fumarate, fingolimod, and ocrelizumab. MAIN OUTCOMES AND MEASURES: Primary outcomes were annualized relapse rate (ARR) and time to first relapse. Secondary outcomes were confirmed disability accumulation, disability improvement, and subsequent treatment discontinuation, with the comparisons for the first 2 limited to fingolimod and ocrelizumab due to the small number of patients taking dimethyl fumarate. The associations were analyzed after balancing covariates using an inverse probability of treatment weighting method. RESULTS: Among 66 840 patients with RRMS, 1744 had used natalizumab for 6 months or longer and were switched to dimethyl fumarate, fingolimod, or ocrelizumab within 3 months of natalizumab discontinuation. After excluding 358 patients without baseline data, a total of 1386 patients (mean [SD] age, 41.3 [10.6] years; 990 female [71%]) switched to dimethyl fumarate (138 [9.9%]), fingolimod (823 [59.4%]), or ocrelizumab (425 [30.7%]) after natalizumab. The ARR for ea
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- 2023
7. The risk of secondary progressive multiple sclerosis is geographically determined but modifiable
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Sharmin, S, Roos, I, Simpson-Yap, S, Malpes, C, Sanchez, MM, Ozakbas, S, Horakova, D, Havrdova, EK, Patti, F, Alroughani, R, Izquierdo, G, Eichau, S, Boz, C, Zakaria, M, Onofrj, M, Lugaresi, A, Weinstock-Guttman, B, Prat, A, Girard, M, Duquette, P, Terzi, M, Amato, MP, Karabudak, R, Grand'Maison, F, Khoury, SJ, Grammond, P, Lechner-Scott, J, Buzzard, K, Skibina, O, van der Walt, A, Butzkueven, H, Turkoglu, R, Altintas, A, Maimone, D, Kermode, A, Shalaby, N, Pesch, VV, Butler, E, Sidhom, Y, Gouider, R, Mrabet, S, Gerlach, O, Soysal, A, Barnett, M, Kuhle, J, Hughes, S, Sa, MJ, Hodgkinson, S, Oreja-Guevara, C, Ampapa, R, Petersen, T, Ramo-Tello, C, Spitaleri, D, McCombe, P, Taylor, B, Prevost, J, Foschi, M, Slee, M, McGuigan, C, Laureys, G, Hijfte, LV, de Gans, K, Solaro, C, Oh, J, Macdonell, R, Aguera-Morales, E, Singhal, B, Gray, O, Garber, J, Wijmeersch, BV, Simu, M, Castillo-Trivino, T, Sanchez-Menoyo, JL, Khurana, D, Al-Asmi, A, Al-Harbi, T, Deri, N, Fragoso, Y, Lalive, PH, Sinnige, LGF, Shaw, C, Shuey, N, Csepany, T, Sempere, AP, Moore, F, Decoo, D, Willekens, B, Gobbi, C, Massey, J, Hardy, T, Parratt, J, Kalincik, T, Sharmin, S, Roos, I, Simpson-Yap, S, Malpes, C, Sanchez, MM, Ozakbas, S, Horakova, D, Havrdova, EK, Patti, F, Alroughani, R, Izquierdo, G, Eichau, S, Boz, C, Zakaria, M, Onofrj, M, Lugaresi, A, Weinstock-Guttman, B, Prat, A, Girard, M, Duquette, P, Terzi, M, Amato, MP, Karabudak, R, Grand'Maison, F, Khoury, SJ, Grammond, P, Lechner-Scott, J, Buzzard, K, Skibina, O, van der Walt, A, Butzkueven, H, Turkoglu, R, Altintas, A, Maimone, D, Kermode, A, Shalaby, N, Pesch, VV, Butler, E, Sidhom, Y, Gouider, R, Mrabet, S, Gerlach, O, Soysal, A, Barnett, M, Kuhle, J, Hughes, S, Sa, MJ, Hodgkinson, S, Oreja-Guevara, C, Ampapa, R, Petersen, T, Ramo-Tello, C, Spitaleri, D, McCombe, P, Taylor, B, Prevost, J, Foschi, M, Slee, M, McGuigan, C, Laureys, G, Hijfte, LV, de Gans, K, Solaro, C, Oh, J, Macdonell, R, Aguera-Morales, E, Singhal, B, Gray, O, Garber, J, Wijmeersch, BV, Simu, M, Castillo-Trivino, T, Sanchez-Menoyo, JL, Khurana, D, Al-Asmi, A, Al-Harbi, T, Deri, N, Fragoso, Y, Lalive, PH, Sinnige, LGF, Shaw, C, Shuey, N, Csepany, T, Sempere, AP, Moore, F, Decoo, D, Willekens, B, Gobbi, C, Massey, J, Hardy, T, Parratt, J, and Kalincik, T
- Abstract
Geographical variations in the incidence and prevalence of multiple sclerosis have been reported globally. Latitude as a surrogate for exposure to ultraviolet radiation but also other lifestyle and environmental factors are regarded as drivers of this variation. No previous studies evaluated geographical variation in the risk of secondary progressive multiple sclerosis, an advanced form of multiple sclerosis that is characterized by steady accrual of irreversible disability. We evaluated differences in the risk of secondary progressive multiple sclerosis in relation to latitude and country of residence, modified by high-to-moderate efficacy immunotherapy in a geographically diverse cohort of patients with relapsing-remitting multiple sclerosis. The study included relapsing-remitting multiple sclerosis patients from the global MSBase registry with at least one recorded assessment of disability. Secondary progressive multiple sclerosis was identified as per clinician diagnosis. Sensitivity analyses used the operationalized definition of secondary progressive multiple sclerosis and the Swedish decision tree algorithm. A proportional hazards model was used to estimate the cumulative risk of secondary progressive multiple sclerosis by country of residence (latitude), adjusted for sex, age at disease onset, time from onset to relapsing-remitting phase, disability (Multiple Sclerosis Severity Score) and relapse activity at study inclusion, national multiple sclerosis prevalence, government health expenditure, and proportion of time treated with high-to-moderate efficacy disease-modifying therapy. Geographical variation in time from relapsing-remitting phase to secondary progressive phase of multiple sclerosis was modelled through a proportional hazards model with spatially correlated frailties. We included 51 126 patients (72% female) from 27 countries. The median survival time from relapsing-remitting phase to secondary progressive multiple sclerosis among all patients wa
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- 2023
8. A plain language summary on the effectiveness of cladribine tablets compared with other oral treatments for multiple sclerosis: results from the MSBase registry
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Spelman, T, Ozakbas, S, Alroughani, R, Terzi, M, Hodgkinson, S, Laureys, G, Kalincik, T, Van der Walt, A, Yamout, B, Lechner-Scott, J, Soysal, A, Kuhle, J, Sanchez-Menoyo, JL, Morgado, YB, Spitaleri, DLA, van Pesch, V, Horakova, D, Ampapa, R, Patti, F, Macdonell, R, Al-Asmi, A, Gerlach, O, Oh, J, Altintas, A, Tundia, N, Wong, SL, Butzkueven, H, MSBase, SG, Spelman, T, Ozakbas, S, Alroughani, R, Terzi, M, Hodgkinson, S, Laureys, G, Kalincik, T, Van der Walt, A, Yamout, B, Lechner-Scott, J, Soysal, A, Kuhle, J, Sanchez-Menoyo, JL, Morgado, YB, Spitaleri, DLA, van Pesch, V, Horakova, D, Ampapa, R, Patti, F, Macdonell, R, Al-Asmi, A, Gerlach, O, Oh, J, Altintas, A, Tundia, N, Wong, SL, Butzkueven, H, and MSBase, SG
- Abstract
WHAT IS THIS SUMMARY ABOUT?: Patient registries contain anonymous data from people who share the same medical condition. The MSBase registry contains information from over 80,000 people living with multiple sclerosis (MS) across 41 countries. Using information from the MSBase registry, the GLIMPSE (Generating Learnings In MultiPle SclErosis) study looked at real-life outcomes in 3475 people living with MS who were treated with cladribine tablets (Mavenclad®) compared with other oral treatments. WHAT WERE THE RESULTS?: Results showed that people treated with cladribine tablets stayed on treatment for longer than other treatments given by mouth. They also had fewer relapses (also called flare ups of symptoms) than people who received a different oral treatment for their MS. WHAT DO THE RESULTS MEAN?: The results provide evidence that, compared with other oral treatments for MS, cladribine tablets are an effective medicine for people living with MS.
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- 2023
9. Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis
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Diouf, I, Malpas, CB, Sharmin, S, Roos, I, Horakova, D, Havrdova, EK, Patti, F, Shaygannejad, V, Ozakbas, S, Izquierdo, G, Eichau, S, 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, Buzzard, K, Skibina, O, Yamout, B, Altintas, A, Gerlach, O, van Pesch, V, Blanco, Y, Maimone, D, Lechner-Scott, J, Bergamaschi, R, Karabudak, R, Iuliano, G, McGuigan, C, Cartechini, E, Barnett, M, Hughes, S, Sa, MJ, Solaro, C, Kappos, L, Ramo-Tello, C, Cristiano, E, Hodgkinson, S, Spitaleri, D, Soysal, A, Petersen, T, Slee, M, Butler, E, Granella, F, de Gans, K, McCombe, P, Ampapa, R, Van Wijmeersch, B, van der Walt, A, Butzkueven, H, Prevost, J, Sinnige, LGF, Sanchez-Menoyo, JL, Vucic, S, Laureys, G, Van Hijfte, L, Khurana, D, Macdonell, R, Gouider, R, Castillo-Trivino, T, Gray, O, Aguera-Morales, E, Al-Asmi, A, Shaw, C, Deri, N, Al-Harbi, T, Fragoso, Y, Csepany, T, Sempere, AP, Trevino-Frenk, I, Schepel, J, Moore, F, Kalincik, T, Diouf, I, Malpas, CB, Sharmin, S, Roos, I, Horakova, D, Havrdova, EK, Patti, F, Shaygannejad, V, Ozakbas, S, Izquierdo, G, Eichau, S, 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, Buzzard, K, Skibina, O, Yamout, B, Altintas, A, Gerlach, O, van Pesch, V, Blanco, Y, Maimone, D, Lechner-Scott, J, Bergamaschi, R, Karabudak, R, Iuliano, G, McGuigan, C, Cartechini, E, Barnett, M, Hughes, S, Sa, MJ, Solaro, C, Kappos, L, Ramo-Tello, C, Cristiano, E, Hodgkinson, S, Spitaleri, D, Soysal, A, Petersen, T, Slee, M, Butler, E, Granella, F, de Gans, K, McCombe, P, Ampapa, R, Van Wijmeersch, B, van der Walt, A, Butzkueven, H, Prevost, J, Sinnige, LGF, Sanchez-Menoyo, JL, Vucic, S, Laureys, G, Van Hijfte, L, Khurana, D, Macdonell, R, Gouider, R, Castillo-Trivino, T, Gray, O, Aguera-Morales, E, Al-Asmi, A, Shaw, C, Deri, N, Al-Harbi, T, Fragoso, Y, Csepany, T, Sempere, AP, Trevino-Frenk, I, Schepel, J, Moore, F, and Kalincik, T
- 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.
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- 2023
10. Effectiveness of multiple disease-modifying therapies in relapsing-remitting multiple sclerosis: causal inference to emulate a multiarm randomised trial
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Diouf, I, Malpas, CB, Sharmin, S, Roos, I, Horakova, D, Kubala Havrdova, E, Patti, F, Shaygannejad, V, Ozakbas, S, Eichau, S, Onofrj, M, Lugaresi, A, Alroughani, R, Prat, A, Duquette, P, Terzi, M, Boz, C, Grand'Maison, F, Sola, P, Ferraro, D, Grammond, P, Yamout, B, Altintas, A, Gerlach, O, Lechner-Scott, J, Bergamaschi, R, Karabudak, R, Iuliano, G, McGuigan, C, Cartechini, E, Hughes, S, Sa, MJ, Solaro, C, Kappos, L, Hodgkinson, S, Slee, M, Granella, F, de Gans, K, McCombe, PA, Ampapa, R, van der Walt, A, Butzkueven, H, Sanchez-Menoyo, JL, Vucic, S, Laureys, G, Sidhom, Y, Gouider, R, Castillo-Trivino, T, Gray, O, Aguera-Morales, E, Al-Asmi, A, Shaw, C, Al-Harbi, TM, Csepany, T, Sempere, AP, Frenk, IT, Stuart, EA, Kalincik, T, Diouf, I, Malpas, CB, Sharmin, S, Roos, I, Horakova, D, Kubala Havrdova, E, Patti, F, Shaygannejad, V, Ozakbas, S, Eichau, S, Onofrj, M, Lugaresi, A, Alroughani, R, Prat, A, Duquette, P, Terzi, M, Boz, C, Grand'Maison, F, Sola, P, Ferraro, D, Grammond, P, Yamout, B, Altintas, A, Gerlach, O, Lechner-Scott, J, Bergamaschi, R, Karabudak, R, Iuliano, G, McGuigan, C, Cartechini, E, Hughes, S, Sa, MJ, Solaro, C, Kappos, L, Hodgkinson, S, Slee, M, Granella, F, de Gans, K, McCombe, PA, Ampapa, R, van der Walt, A, Butzkueven, H, Sanchez-Menoyo, JL, Vucic, S, Laureys, G, Sidhom, Y, Gouider, R, Castillo-Trivino, T, Gray, O, Aguera-Morales, E, Al-Asmi, A, Shaw, C, Al-Harbi, TM, Csepany, T, Sempere, AP, Frenk, IT, Stuart, EA, and Kalincik, T
- Abstract
BACKGROUND: Simultaneous comparisons of multiple disease-modifying therapies for relapsing-remitting multiple sclerosis (RRMS) over an extended follow-up are lacking. Here we emulate a randomised trial simultaneously comparing the effectiveness of six commonly used therapies over 5 years. METHODS: Data from 74 centres in 35 countries were sourced from MSBase. For each patient, the first eligible intervention was analysed, censoring at change/discontinuation of treatment. The compared interventions included natalizumab, fingolimod, dimethyl fumarate, teriflunomide, interferon beta, glatiramer acetate and no treatment. Marginal structural Cox models (MSMs) were used to estimate the average treatment effects (ATEs) and the average treatment effects among the treated (ATT), rebalancing the compared groups at 6-monthly intervals on age, sex, birth-year, pregnancy status, treatment, relapses, disease duration, disability and disease course. The outcomes analysed were incidence of relapses, 12-month confirmed disability worsening and improvement. RESULTS: 23 236 eligible patients were diagnosed with RRMS or clinically isolated syndrome. Compared with glatiramer acetate (reference), several therapies showed a superior ATE in reducing relapses: natalizumab (HR=0.44, 95% CI=0.40 to 0.50), fingolimod (HR=0.60, 95% CI=0.54 to 0.66) and dimethyl fumarate (HR=0.78, 95% CI=0.66 to 0.92). Further, natalizumab (HR=0.43, 95% CI=0.32 to 0.56) showed a superior ATE in reducing disability worsening and in disability improvement (HR=1.32, 95% CI=1.08 to 1.60). The pairwise ATT comparisons also showed superior effects of natalizumab followed by fingolimod on relapses and disability. CONCLUSIONS: The effectiveness of natalizumab and fingolimod in active RRMS is superior to dimethyl fumarate, teriflunomide, glatiramer acetate and interferon beta. This study demonstrates the utility of MSM in emulating trials to compare clinical effectiveness among multiple interventions simultaneously.
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- 2023
11. Comparative Effectiveness of Autologous Hematopoietic Stem Cell Transplant vs Fingolimod, Natalizumab, and Ocrelizumab in Highly Active Relapsing-Remitting Multiple Sclerosis
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Kalincik, T, Sharmin, S, Roos, I, Freedman, MS, Atkins, H, Burman, J, Massey, J, Sutton, I, Withers, B, Macdonell, R, Grigg, A, Torkildsen, O, Bo, L, Lehmann, AK, Havrdova, EK, Krasulova, E, Trneny, M, Kozak, T, van der Walt, A, Butzkueven, H, McCombe, P, Skibina, O, Lechner-Scott, J, Willekens, B, Cartechini, E, Ozakbas, S, Alroughani, R, Kuhle, J, Patti, F, Duquette, P, Lugaresi, A, Khoury, SJ, Slee, M, Turkoglu, R, Hodgkinson, S, John, N, Maimone, D, Sa, MJ, van Pesch, V, Gerlach, O, Laureys, G, Van Hijfte, L, Karabudak, R, Spitaleri, D, Csepany, T, Gouider, R, Castillo-Trivino, T, Taylor, B, Sharrack, B, Snowden, JA, Kalincik, T, Sharmin, S, Roos, I, Freedman, MS, Atkins, H, Burman, J, Massey, J, Sutton, I, Withers, B, Macdonell, R, Grigg, A, Torkildsen, O, Bo, L, Lehmann, AK, Havrdova, EK, Krasulova, E, Trneny, M, Kozak, T, van der Walt, A, Butzkueven, H, McCombe, P, Skibina, O, Lechner-Scott, J, Willekens, B, Cartechini, E, Ozakbas, S, Alroughani, R, Kuhle, J, Patti, F, Duquette, P, Lugaresi, A, Khoury, SJ, Slee, M, Turkoglu, R, Hodgkinson, S, John, N, Maimone, D, Sa, MJ, van Pesch, V, Gerlach, O, Laureys, G, Van Hijfte, L, Karabudak, R, Spitaleri, D, Csepany, T, Gouider, R, Castillo-Trivino, T, Taylor, B, Sharrack, B, and Snowden, JA
- Abstract
IMPORTANCE: Autologous hematopoietic stem cell transplant (AHSCT) is available for treatment of highly active multiple sclerosis (MS). OBJECTIVE: To compare the effectiveness of AHSCT vs fingolimod, natalizumab, and ocrelizumab in relapsing-remitting MS by emulating pairwise trials. DESIGN, SETTING, AND PARTICIPANTS: This comparative treatment effectiveness study included 6 specialist MS centers with AHSCT programs and international MSBase registry between 2006 and 2021. The study included patients with relapsing-remitting MS treated with AHSCT, fingolimod, natalizumab, or ocrelizumab with 2 or more years study follow-up including 2 or more disability assessments. Patients were matched on a propensity score derived from clinical and demographic characteristics. EXPOSURE: AHSCT vs fingolimod, natalizumab, or ocrelizumab. MAIN OUTCOMES: Pairwise-censored groups were compared on annualized relapse rates (ARR) and freedom from relapses and 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening and improvement. RESULTS: Of 4915 individuals, 167 were treated with AHSCT; 2558, fingolimod; 1490, natalizumab; and 700, ocrelizumab. The prematch AHSCT cohort was younger and with greater disability than the fingolimod, natalizumab, and ocrelizumab cohorts; the matched groups were closely aligned. The proportion of women ranged from 65% to 70%, and the mean (SD) age ranged from 35.3 (9.4) to 37.1 (10.6) years. The mean (SD) disease duration ranged from 7.9 (5.6) to 8.7 (5.4) years, EDSS score ranged from 3.5 (1.6) to 3.9 (1.9), and frequency of relapses ranged from 0.77 (0.94) to 0.86 (0.89) in the preceding year. Compared with the fingolimod group (769 [30.0%]), AHSCT (144 [86.2%]) was associated with fewer relapses (ARR: mean [SD], 0.09 [0.30] vs 0.20 [0.44]), similar risk of disability worsening (hazard ratio [HR], 1.70; 95% CI, 0.91-3.17), and higher chance of disability improvement (HR, 2.70; 95% CI, 1.71-4.26) over 5 years. Compared with natalizumab (730
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- 2023
12. Rituximab vs Ocrelizumab in Relapsing-Remitting Multiple Sclerosis
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Roos, I, Hughes, S, McDonnell, G, Malpas, CB, Sharmin, S, Boz, C, Alroughani, R, Ozakbas, S, Buzzard, K, Skibina, O, van der Walt, A, Butzkueven, H, Lechner-Scott, J, Kuhle, J, Terzi, M, Laureys, G, Van Hijfte, L, John, N, Grammond, P, Grand'Maison, F, Soysal, A, Jensen, AV, Rasmussen, PV, Svendsen, KB, Barzinji, I, Nielsen, HH, Sejbaek, T, Prakash, S, Stilund, MLM, Weglewski, A, Issa, NM, Kant, M, Sellebjerg, F, Gray, O, Magyari, M, Kalincik, T, MSBase, SG, Danish, MSRSG, Roos, I, Hughes, S, McDonnell, G, Malpas, CB, Sharmin, S, Boz, C, Alroughani, R, Ozakbas, S, Buzzard, K, Skibina, O, van der Walt, A, Butzkueven, H, Lechner-Scott, J, Kuhle, J, Terzi, M, Laureys, G, Van Hijfte, L, John, N, Grammond, P, Grand'Maison, F, Soysal, A, Jensen, AV, Rasmussen, PV, Svendsen, KB, Barzinji, I, Nielsen, HH, Sejbaek, T, Prakash, S, Stilund, MLM, Weglewski, A, Issa, NM, Kant, M, Sellebjerg, F, Gray, O, Magyari, M, Kalincik, T, MSBase, SG, and Danish, MSRSG
- Abstract
IMPORTANCE: Ocrelizumab, a humanized monoclonal antibody targeted against CD20+ B cells, reduces the frequency of relapses by 46% and disability worsening by 40% compared with interferon beta 1a in relapsing-remitting multiple sclerosis (MS). Rituximab, a chimeric monoclonal anti-CD20 agent, is often prescribed as an off-label alternative to ocrelizumab. OBJECTIVE: To evaluate whether the effectiveness of rituximab is noninferior to ocrelizumab in relapsing-remitting MS. DESIGN, SETTING, AND PARTICIPANTS: This was an observational cohort study conducted between January 2015 and March 2021. Patients were included in the treatment group for the duration of study therapy and were recruited from the MSBase registry and Danish MS Registry (DMSR). Included patients had a history of relapsing-remitting MS treated with ocrelizumab or rituximab, a minimum 6 months of follow-up, and sufficient data to calculate the propensity score. Patients with comparable baseline characteristics were 1:6 matched with propensity score on age, sex, MS duration, disability (Expanded Disability Status Scale), prior relapse rate, prior therapy, disease activity (relapses, disability accumulation, or both), magnetic resonance imaging lesion burden (missing values imputed), and country. EXPOSURE: Treatment with ocrelizumab or rituximab after 2015. MAIN OUTCOMES AND MEASURES: Noninferiority comparison of annualized rate of relapses (ARRs), with a prespecified noninferiority margin of 1.63 rate ratio. Secondary end points were relapse and 6-month confirmed disability accumulation in pairwise-censored groups. RESULTS: Of the 6027 patients with MS who were treated with ocrelizumab or rituximab, a total of 1613 (mean [SD] age; 42.0 [10.8] years; 1089 female [68%]) fulfilled the inclusion criteria and were included in the analysis (898 MSBase, 715 DMSR). A total of 710 patients treated with ocrelizumab (414 MSBase, 296 DMSR) were matched with 186 patients treated with rituximab (110 MSBase, 76 DMSR). O
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- 2023
13. Disability accrual in primary and secondary progressive multiple sclerosis
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Harding-Forrester, S, Roos, I, Nguyen, A-L, Malpas, CB, Diouf, I, Moradi, N, Sharmin, S, Izquierdo, G, Eichau, S, Patti, F, Horakova, D, Kubala Havrdova, E, Prat, A, Girard, M, Duquette, P, Maison, FG, Onofrj, M, Lugaresi, A, Grammond, P, Ozakbas, S, Amato, MP, Gerlach, O, Sola, P, Ferraro, D, Buzzard, K, Skibina, O, Lechner-Scott, J, Alroughani, R, Boz, C, Van Pesch, V, Cartechini, E, Terzi, M, Maimone, D, Ramo-Tello, C, Yamout, B, Khoury, SJ, La Spitaleri, D, Sa, MJ, Blanco, Y, Granella, F, Slee, M, Butler, E, Sidhom, Y, Gouider, R, Bergamaschi, R, Karabudak, R, Ampapa, R, Sanchez-Menoyo, JL, Prevost, J, Castillo-Trivino, T, McCombe, PA, Macdonell, R, Laureys, G, Van Hijfte, L, Oh, J, Altintas, A, de Gans, K, Turkoglu, R, van der Walt, A, Butzkueven, H, Vucic, S, Barnett, M, Cristiano, E, Hodgkinson, S, Iuliano, G, Kappos, L, Kuhle, J, Shaygannejad, V, Soysal, A, Weinstock-Guttman, B, Van Wijmeersch, B, Kalincik, T, Harding-Forrester, S, Roos, I, Nguyen, A-L, Malpas, CB, Diouf, I, Moradi, N, Sharmin, S, Izquierdo, G, Eichau, S, Patti, F, Horakova, D, Kubala Havrdova, E, Prat, A, Girard, M, Duquette, P, Maison, FG, Onofrj, M, Lugaresi, A, Grammond, P, Ozakbas, S, Amato, MP, Gerlach, O, Sola, P, Ferraro, D, Buzzard, K, Skibina, O, Lechner-Scott, J, Alroughani, R, Boz, C, Van Pesch, V, Cartechini, E, Terzi, M, Maimone, D, Ramo-Tello, C, Yamout, B, Khoury, SJ, La Spitaleri, D, Sa, MJ, Blanco, Y, Granella, F, Slee, M, Butler, E, Sidhom, Y, Gouider, R, Bergamaschi, R, Karabudak, R, Ampapa, R, Sanchez-Menoyo, JL, Prevost, J, Castillo-Trivino, T, McCombe, PA, Macdonell, R, Laureys, G, Van Hijfte, L, Oh, J, Altintas, A, de Gans, K, Turkoglu, R, van der Walt, A, Butzkueven, H, Vucic, S, Barnett, M, Cristiano, E, Hodgkinson, S, Iuliano, G, Kappos, L, Kuhle, J, Shaygannejad, V, Soysal, A, Weinstock-Guttman, B, Van Wijmeersch, B, and Kalincik, T
- Abstract
Background: Some studies comparing primary and secondary progressive multiple sclerosis (PPMS, SPMS) report similar ages at onset of the progressive phase and similar rates of subsequent disability accrual. Others report later onset and/or faster accrual in SPMS. Comparisons have been complicated by regional cohort effects, phenotypic differences in sex ratio and management and variable diagnostic criteria for SPMS. Methods: We compared disability accrual in PPMS and operationally diagnosed SPMS in the international, clinic-based MSBase cohort. Inclusion required PPMS or SPMS with onset at age ≥18 years since 1995. We estimated Andersen-Gill hazard ratios for disability accrual on the Expanded Disability Status Scale (EDSS), adjusted for sex, age, baseline disability, EDSS score frequency and drug therapies, with centre and patient as random effects. We also estimated ages at onset of the progressive phase (Kaplan-Meier) and at EDSS milestones (Turnbull). Analyses were replicated with physician-diagnosed SPMS. Results: Included patients comprised 1872 with PPMS (47% men; 50% with activity) and 2575 with SPMS (32% men; 40% with activity). Relative to PPMS, SPMS had older age at onset of the progressive phase (median 46.7 years (95% CI 46.2-47.3) vs 43.9 (43.3-44.4); p<0.001), greater baseline disability, slower disability accrual (HR 0.86 (0.78-0.94); p<0.001) and similar age at wheelchair dependence. Conclusions: We demonstrate later onset of the progressive phase and slower disability accrual in SPMS versus PPMS. This may balance greater baseline disability in SPMS, yielding convergent disability trajectories across phenotypes. The different rates of disability accrual should be considered before amalgamating PPMS and SPMS in clinical trials.
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- 2023
14. Comparative effectiveness in multiple sclerosis: A methodological comparison
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Roos, I, Diouf, I, Sharmin, S, Horakova, D, Havrdova, EK, Patti, F, Shaygannejad, V, Ozakbas, S, Izquierdo, G, Eichau, S, Onofrj, M, Lugaresi, A, Alroughani, R, Prat, A, Girard, M, Duquette, P, Terzi, M, Boz, C, Grand'Maison, F, Sola, P, Ferraro, D, Grammond, P, Turkoglu, R, Buzzard, K, Skibina, O, Yamou, B, Altintas, A, Gerlach, O, van Pesch, V, Blanco, Y, Maimone, D, Lechner-Scott, J, Bergamaschi, R, Karabudak, R, McGuigan, C, Cartechini, E, Barnett, M, Hughes, S, Sa, MJ, Solaro, C, Ramo-Tello, C, Hodgkinson, S, Spitaleri, D, Soysal, A, Petersen, T, Granella, F, de Gans, K, McCombe, P, Ampapa, R, Van Wijmeersch, B, van der Walt, A, Butzkueven, H, Prevost, J, Sanchez-Menoyo, JL, Laureys, G, Gouider, R, Castillo-Trivino, T, Gray, O, Aguera-Morales, E, Al-Asmi, A, Shaw, C, Deri, N, Al-Harbi, T, Fragoso, Y, Csepany, T, Sempere, AP, Trevino-Frenk, I, Schepel, J, Moore, F, Malpas, C, Kalincik, T, Roos, I, Diouf, I, Sharmin, S, Horakova, D, Havrdova, EK, Patti, F, Shaygannejad, V, Ozakbas, S, Izquierdo, G, Eichau, S, Onofrj, M, Lugaresi, A, Alroughani, R, Prat, A, Girard, M, Duquette, P, Terzi, M, Boz, C, Grand'Maison, F, Sola, P, Ferraro, D, Grammond, P, Turkoglu, R, Buzzard, K, Skibina, O, Yamou, B, Altintas, A, Gerlach, O, van Pesch, V, Blanco, Y, Maimone, D, Lechner-Scott, J, Bergamaschi, R, Karabudak, R, McGuigan, C, Cartechini, E, Barnett, M, Hughes, S, Sa, MJ, Solaro, C, Ramo-Tello, C, Hodgkinson, S, Spitaleri, D, Soysal, A, Petersen, T, Granella, F, de Gans, K, McCombe, P, Ampapa, R, Van Wijmeersch, B, van der Walt, A, Butzkueven, H, Prevost, J, Sanchez-Menoyo, JL, Laureys, G, Gouider, R, Castillo-Trivino, T, Gray, O, Aguera-Morales, E, Al-Asmi, A, Shaw, C, Deri, N, Al-Harbi, T, Fragoso, Y, Csepany, T, Sempere, AP, Trevino-Frenk, I, Schepel, J, Moore, F, Malpas, C, and Kalincik, T
- Abstract
BACKGROUND: In the absence of evidence from randomised controlled trials, observational data can be used to emulate clinical trials and guide clinical decisions. Observational studies are, however, susceptible to confounding and bias. Among the used techniques to reduce indication bias are propensity score matching and marginal structural models. OBJECTIVE: To use the comparative effectiveness of fingolimod vs natalizumab to compare the results obtained with propensity score matching and marginal structural models. METHODS: Patients with clinically isolated syndrome or relapsing remitting MS who were treated with either fingolimod or natalizumab were identified in the MSBase registry. Patients were propensity score matched, and inverse probability of treatment weighted at six monthly intervals, using the following variables: age, sex, disability, MS duration, MS course, prior relapses, and prior therapies. Studied outcomes were cumulative hazard of relapse, disability accumulation, and disability improvement. RESULTS: 4608 patients (1659 natalizumab, 2949 fingolimod) fulfilled inclusion criteria, and were propensity score matched or repeatedly reweighed with marginal structural models. Natalizumab treatment was associated with a lower probability of relapse (PS matching: HR 0.67 [95% CI 0.62-0.80]; marginal structural model: 0.71 [0.62-0.80]), and higher probability of disability improvement (PS matching: 1.21 [1.02 -1.43]; marginal structural model 1.43 1.19 -1.72]). There was no evidence of a difference in the magnitude of effect between the two methods. CONCLUSIONS: The relative effectiveness of two therapies can be efficiently compared by either marginal structural models or propensity score matching when applied in clearly defined clinical contexts and in sufficiently powered cohorts.
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- 2023
15. Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis
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Daruwalla, C, Shaygannejad, V, Ozakbas, S, Havrdova, EK, Horakova, D, Alroughani, R, Boz, C, Patti, F, Onofrj, M, Lugaresi, A, Eichau, S, Girard, M, Prat, A, Duquette, P, Yamout, B, Khoury, SJ, Sajedi, SA, Turkoglu, R, Altintas, A, Skibina, O, Buzzard, K, Grammond, P, Karabudak, R, van der Walt, A, Butzkueven, H, Maimone, D, Lechner-Scott, J, Soysal, A, John, N, Prevost, J, Spitaleri, D, Ramo-Tello, C, Gerlach, O, Iuliano, G, Foschi, M, Ampapa, R, van Pesch, V, Barnett, M, Shalaby, N, D'hooghe, M, Kuhle, J, Sa, MJ, Fabis-Pedrini, M, Kermode, A, Mrabet, S, Gouider, R, Hodgkinson, S, Laureys, G, Van Hijfte, L, Macdonell, R, Oreja-Guevara, C, Cristiano, E, McCombe, P, Sanchez-Menoyo, JL, Singhal, B, Blanco, Y, Hughes, S, Garber, J, Solaro, C, McGuigan, C, Taylor, B, de Gans, K, Habek, M, Al-Asmi, A, Mihaela, S, Castillo Trivino, T, Al-Harbi, T, Rojas, JI, Gray, O, Khurana, D, Van Wijmeersch, B, Grigoriadis, N, Inshasi, J, Oh, J, Aguera-Morales, E, Fragoso, Y, Moore, F, Shaw, C, Baghbanian, SM, Shuey, N, Willekens, B, Hardy, TA, Decoo, D, Sempere, AP, Field, D, Wynford-Thomas, R, Cunniffe, NG, Roos, I, Malpas, CB, Coles, AJ, Kalincik, T, Brown, JWL, MSBase, SG, Daruwalla, C, Shaygannejad, V, Ozakbas, S, Havrdova, EK, Horakova, D, Alroughani, R, Boz, C, Patti, F, Onofrj, M, Lugaresi, A, Eichau, S, Girard, M, Prat, A, Duquette, P, Yamout, B, Khoury, SJ, Sajedi, SA, Turkoglu, R, Altintas, A, Skibina, O, Buzzard, K, Grammond, P, Karabudak, R, van der Walt, A, Butzkueven, H, Maimone, D, Lechner-Scott, J, Soysal, A, John, N, Prevost, J, Spitaleri, D, Ramo-Tello, C, Gerlach, O, Iuliano, G, Foschi, M, Ampapa, R, van Pesch, V, Barnett, M, Shalaby, N, D'hooghe, M, Kuhle, J, Sa, MJ, Fabis-Pedrini, M, Kermode, A, Mrabet, S, Gouider, R, Hodgkinson, S, Laureys, G, Van Hijfte, L, Macdonell, R, Oreja-Guevara, C, Cristiano, E, McCombe, P, Sanchez-Menoyo, JL, Singhal, B, Blanco, Y, Hughes, S, Garber, J, Solaro, C, McGuigan, C, Taylor, B, de Gans, K, Habek, M, Al-Asmi, A, Mihaela, S, Castillo Trivino, T, Al-Harbi, T, Rojas, JI, Gray, O, Khurana, D, Van Wijmeersch, B, Grigoriadis, N, Inshasi, J, Oh, J, Aguera-Morales, E, Fragoso, Y, Moore, F, Shaw, C, Baghbanian, SM, Shuey, N, Willekens, B, Hardy, TA, Decoo, D, Sempere, AP, Field, D, Wynford-Thomas, R, Cunniffe, NG, Roos, I, Malpas, CB, Coles, AJ, Kalincik, T, Brown, JWL, and MSBase, SG
- Abstract
BACKGROUND: The prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear. OBJECTIVE: To determine whether early non-disabling relapses predict disability accumulation in RRMS. METHODS: We redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up. RESULTS: People who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated (n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs (n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs (n = 572 vs 3534; HR = 0.90, 95% CI = 0.71-1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically. CONCLUSION: This study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions.
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- 2023
16. Comparative effectiveness of cladribine tablets versus other oral disease-modifying treatments for multiple sclerosis: Results from MSBase registry
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Spelman, T, Ozakbas, S, Alroughani, R, Terzi, M, Hodgkinson, S, Laureys, G, Kalincik, T, Van der Walt, A, Yamout, B, Lechner-Scott, J, Soysal, A, Kuhle, J, Sanchez-Menoyo, JL, Morgado, YB, La Spitaleri, D, van Pesch, V, Horakova, D, Ampapa, R, Patti, F, Macdonell, R, Al-Asmi, A, Gerlach, O, Oh, J, Altintas, A, Tundia, N, Wong, SL, Butzkueven, H, Spelman, T, Ozakbas, S, Alroughani, R, Terzi, M, Hodgkinson, S, Laureys, G, Kalincik, T, Van der Walt, A, Yamout, B, Lechner-Scott, J, Soysal, A, Kuhle, J, Sanchez-Menoyo, JL, Morgado, YB, La Spitaleri, D, van Pesch, V, Horakova, D, Ampapa, R, Patti, F, Macdonell, R, Al-Asmi, A, Gerlach, O, Oh, J, Altintas, A, Tundia, N, Wong, SL, and Butzkueven, H
- Abstract
BACKGROUND: Effectiveness of cladribine tablets, an oral disease-modifying treatment (DMT) for multiple sclerosis (MS), was established in clinical trials and confirmed with real-world experience. OBJECTIVES: Use real-world data to compare treatment patterns and clinical outcomes in people with MS (pwMS) treated with cladribine tablets versus other oral DMTs. METHODS: Retrospective treatment comparisons were based on data from the international MSBase registry. Eligible pwMS started treatment with cladribine, fingolimod, dimethyl fumarate, or teriflunomide tablets from 2018 to mid-2021 and were censored at treatment discontinuation/switch, death, loss to follow-up, pregnancy, or study period end. Treatment persistence was evaluated as time to discontinuation/switch; relapse outcomes included time to first relapse and annualized relapse rate (ARR). RESULTS: Cohorts included 633 pwMS receiving cladribine tablets, 1195 receiving fingolimod, 912 receiving dimethyl fumarate, and 735 receiving teriflunomide. Individuals treated with fingolimod, dimethyl fumarate, or teriflunomide switched treatment significantly more quickly than matched cladribine tablet cohorts (adjusted hazard ratio (95% confidence interval): 4.00 (2.54-6.32), 7.04 (4.16-11.93), and 6.52 (3.79-11.22), respectively). Cladribine tablet cohorts had significantly longer time-to-treatment discontinuation, time to first relapse, and lower ARR, compared with other oral DMT cohorts. CONCLUSION: Cladribine tablets were associated with a significantly greater real-world treatment persistence and more favorable relapse outcomes than all oral DMT comparators.
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- 2023
17. Early non-disabling relapses are important predictors of disability accumulation in people with relapsing-remitting multiple sclerosis
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Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Daruwalla, C.; Shaygannejad, V.; Ozakbas, S.; Havrdova, EK.; Horakova, D.; Alroughani, R.; Boz, C.; Patti, F.; Onofrj, M.; Lugaresi, A.; Eichau, S.; Girard, M.; Prat, A.; Duquette, P.; Yamout, B.; Khoury, S.J.; Sajedi, S.A.; Turkoglu, R.; Skibina, O.; Buzzard, K.; Grammond, P.; Karabudak, R.; van der Walt, A.; Butzkueven, H.; Maimone, D.; Lechner-Scott, J.; Soysal, A.; John, N.; Prevost, J.; Spitaleri, D.; Ramo-Tello, C.; Gerlach, O.; Iuliano, G.; Foschi, M.; Ampapa, R.; van Pesch, V.; Barnett, M.; Shalaby, N.; D'hooghe, M.; Kuhle, J.; Sa, M.J.; Fabis-Pedrini, M.; Kermode, A.; Mrabet, S.; Gouider, R.; Hodgkinson, S.; Laureys, G.; Van Hijfte, L.; Macdonell, R.; Oreja-Guevara, C.; Cristiano, E.; McCombe, P.; Sanchez-Menoyo, J.L.; Singhal, B.; Blanco, Y.; Hughes, S.; Garber, J.; Solaro, C.; McGuigan, C.; Taylor, B.; de Gans, K.; Habek, M.; Al-Asmi, A.; Mihaela, S.; Castillo Triviño, T.; Al-Harbi, T.; Rojas, J.I.; Gray, O.; Khuran,a D.; Van Wijmeersch, B.; Grigoriadis, N.; Inshasi, J.; Oh, J.; Aguera-Morales, E.; Fragoso, Y.; Moore, F.; Shaw, C.; Baghbanian, S.M.; Shuey, N.; Willekens, B.; Hardy, T.A.; Decoo, D.; Sempere, A.P.; Field, D.; Wynford-Thomas, R.; Cunniffe, NG.; Roos, I.; Malpas, C.B.; Coles, A.J.; Kalincik, T.; Brown, J.W.L., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine, Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Daruwalla, C.; Shaygannejad, V.; Ozakbas, S.; Havrdova, EK.; Horakova, D.; Alroughani, R.; Boz, C.; Patti, F.; Onofrj, M.; Lugaresi, A.; Eichau, S.; Girard, M.; Prat, A.; Duquette, P.; Yamout, B.; Khoury, S.J.; Sajedi, S.A.; Turkoglu, R.; Skibina, O.; Buzzard, K.; Grammond, P.; Karabudak, R.; van der Walt, A.; Butzkueven, H.; Maimone, D.; Lechner-Scott, J.; Soysal, A.; John, N.; Prevost, J.; Spitaleri, D.; Ramo-Tello, C.; Gerlach, O.; Iuliano, G.; Foschi, M.; Ampapa, R.; van Pesch, V.; Barnett, M.; Shalaby, N.; D'hooghe, M.; Kuhle, J.; Sa, M.J.; Fabis-Pedrini, M.; Kermode, A.; Mrabet, S.; Gouider, R.; Hodgkinson, S.; Laureys, G.; Van Hijfte, L.; Macdonell, R.; Oreja-Guevara, C.; Cristiano, E.; McCombe, P.; Sanchez-Menoyo, J.L.; Singhal, B.; Blanco, Y.; Hughes, S.; Garber, J.; Solaro, C.; McGuigan, C.; Taylor, B.; de Gans, K.; Habek, M.; Al-Asmi, A.; Mihaela, S.; Castillo Triviño, T.; Al-Harbi, T.; Rojas, J.I.; Gray, O.; Khuran,a D.; Van Wijmeersch, B.; Grigoriadis, N.; Inshasi, J.; Oh, J.; Aguera-Morales, E.; Fragoso, Y.; Moore, F.; Shaw, C.; Baghbanian, S.M.; Shuey, N.; Willekens, B.; Hardy, T.A.; Decoo, D.; Sempere, A.P.; Field, D.; Wynford-Thomas, R.; Cunniffe, NG.; Roos, I.; Malpas, C.B.; Coles, A.J.; Kalincik, T.; Brown, J.W.L., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), and School of Medicine
- Abstract
Background: the prognostic significance of non-disabling relapses in people with relapsing-remitting multiple sclerosis (RRMS) is unclear. Objective: to determine whether early non-disabling relapses predict disability accumulation in RRMS. Methods: we redefined mild relapses in MSBase as 'non-disabling', and moderate or severe relapses as 'disabling'. We used mixed-effects Cox models to compare 90-day confirmed disability accumulation events in people with exclusively non-disabling relapses within 2 years of RRMS diagnosis to those with no early relapses; and any early disabling relapses. Analyses were stratified by disease-modifying therapy (DMT) efficacy during follow-up. Results: people who experienced non-disabling relapses within 2 years of RRMS diagnosis accumulated more disability than those with no early relapses if they were untreated (n = 285 vs 4717; hazard ratio (HR) = 1.29, 95% confidence interval (CI) = 1.00-1.68) or given platform DMTs (n = 1074 vs 7262; HR = 1.33, 95% CI = 1.15-1.54), but not if given high-efficacy DMTs (n = 572 vs 3534; HR = 0.90, 95% CI = 0.71-1.13) during follow-up. Differences in disability accumulation between those with early non-disabling relapses and those with early disabling relapses were not confirmed statistically. Conclusion: this study suggests that early non-disabling relapses are associated with a higher risk of disability accumulation than no early relapses in RRMS. This risk may be mitigated by high-efficacy DMTs. Therefore, non-disabling relapses should be considered when making treatment decisions., 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 (fellowship nos.1140766 and 1080518, project grant nos. 1129189 and 1083539), the University of Melbourne (Faculty of Medicine, Dentistry and Health Sciences research fellowship), National Institute for Health and Care Research (UK) Advanced Fellowship (grant no. 301728; recipient JWLB) and Academic Clinical Fellowship (grant no. EAN/ACA-006/7488627/C; recipient CD). The MSBase Foundation is a not-for-profit organization that receives support from Roche, Merck, Biogen, Novartis, Bayer Schering, Sanofi Genzyme, and Teva. Role of the Funder/Sponsor: The National Health and Medical Research Council of Australia, the University of Melbourne and the National Institute for Health and Care Research (UK) had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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- 2023
18. Real-world experience with ocrelizumab in primary Progressive multiple sclerosis: Insights from the MSOCR-P cohort, a MSBase Registry sub-study
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Terzi, M., Rojas, J. I., Barnett, M., Fragoso, Y., Cartechini, E., Pucci, E., Willekens, B., Butler, E., Blanco, Y., Grigoriadis, N., Van Hijfte, L., Dirks, P., Liu, C., Rouzic, E. Muros-Le, Butzkueven, H., Al-Harbi, T., Laureys, G., Ozakbas, S., Spelman, T., Alroughani, R., Menoyo, J. L. Sanchez, Van Pesch, V., Kalincik, T., Lechner-Scott, J., Van der Walt, A., Grand'Maison, F., Boz, C., Buzzard, K., and Skibina, O.
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- 2022
19. Real-world data from the MSBase registry in MOG antibody-associated disease: First insights from the MOGAD substudy
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Houston, S., Monif, M., Ozakbas, S., Ramanathan, S., Sanfilippo, P., Chu, M., Ma, K. K., Kalincik, T., Foschi, M., Brilot, F., Laureys, G., Lechner-Scott, J., Van der Walt, A., Willekens, B., Alrhoughani, R., Al-Harbi, T., Habek, M., Butzkueven, H., and Dale, R. C.
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- 2022
20. Efficacy and persistence between dimethyl fumarate, fingolimod, and ocrelizumab after natalizumab cessation
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Macdonell, R., Zhu, C., Kalincik, T., Horakova, D., Zhen, Z., Buzzard, K., Skibina, O., Alroughani, R., Izquierdo, G., Eichau, S., Kuhle, J., Patti, F., Grand'Maison, F., Hodgkinson, S., Grammond, P., Lechner-Scott, J., Butler, E., Prat, A., Girard, M., Butzkueven, H., Van der Walt, A., Merlo, D., Monif, M., Jokubaitis, V., Khoury, S. J., Yamout, B., Garber, J., Kermode, A., Van Hijfte, L., Laureys, G., Boz, C., Terzi, M., Prevost, J., Gerlach, O., Van Wijmeersch, B., Barnett, M., Van Pesch, V., Sa, M. Jose, Slee, M., Ozakbas, S., Weinstock-Guttman, B., and Duquette, P.
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- 2022
21. A non-inferiority study of rituximab versus ocrelizumab in relapsing-remitting multiple sclerosis
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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.
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- 2022
22. β2-Adrenergic receptors protect axons during energetic stress but do not influence basal glio-axonal lactate shuttling in mouse white matter
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Laureys, G., Valentino, M., Demol, F., Zammit, C., Muscat, R., Cambron, M., Kooijman, R., and De Keyser, J.
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- 2014
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23. Comparative Effectiveness and Persistence of Cladribine Tablets from GLIMPSE: Results from the MSBase Registry
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Kalincik, T., Alroughani, R., Ozakbas, SERKAN, Wong, S., Tundia, N., Spelman, T., Van der Walt, A., Terzi, M., Butzkueven, H., Hodgkinson, S., and Laureys, G.
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- 2022
24. Real-World Comparative Effectiveness and Persistence of Cladribine Tablets and Other Oral Disease-Modifying Treatments for Multiple Sclerosis from GLIMPSE: Results from the MSBase Registry
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Spitaleri, D., Kuhle, J., Ozakbas, SERKAN, Patti, F., Ampapa, R., Horakova, D., Soysal, A., Butzkueven, H., Spelman, T., Lechner-Scott, J., Yamout, B., Alroughani, R., Terzi, M., Hodgkinson, S., Sanchez-Menoyo, J., Blanco, Y., Van Pesch, V., Van der Walt, A., Kalincik, T., Laureys, G., Wong, S., Tundia, N., Altintas, A., Oh, J., Gerlach, O., Al-Asmi, A., and Macdonell, R.
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- 2022
25. Association of Latitude and Exposure to Ultraviolet B Radiation With Severity of Multiple Sclerosis: An International Registry Study.
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Vitkova M., Diouf I., Malpas C., Horakova D., Havrdova E.K., Patti F., Ozakbas S., Izquierdo G., Eichau S., Shaygannejad V., Onofrj M., Lugaresi A., Alroughani R., Prat A., Larochelle C., Girard M., Duquette P., Terzi M., Boz C., Grand'Maison F., Sola P., Ferraro D., Grammond P., Butzkueven H., Buzzard K., Skibina O., Yamout B.I., Karabudak R., Gerlach O., Lechner-Scott J., Maimone D., Bergamaschi R., Van Pesch V., Iuliano G., Cartechini E., JosA Sa M., Ampapa R., Barnett M., Hughes S.E., Ramo-Tello C.M., Hodgkinson S., Spitaleri D.L.A., Petersen T., Butler E.G., Slee M., McGuigan C., McCombe P.A., Granella F., Cristiano E., Prevost J., Taylor B.V., Sa Nchez-Menoyo J.L., Laureys G., Van Hijfte L., Vucic S., Macdonell R.A., Gray O., Olascoaga J., Deri N., Fragoso Y.D., Shaw C., Kalincik T., Vitkova M., Diouf I., Malpas C., Horakova D., Havrdova E.K., Patti F., Ozakbas S., Izquierdo G., Eichau S., Shaygannejad V., Onofrj M., Lugaresi A., Alroughani R., Prat A., Larochelle C., Girard M., Duquette P., Terzi M., Boz C., Grand'Maison F., Sola P., Ferraro D., Grammond P., Butzkueven H., Buzzard K., Skibina O., Yamout B.I., Karabudak R., Gerlach O., Lechner-Scott J., Maimone D., Bergamaschi R., Van Pesch V., Iuliano G., Cartechini E., JosA Sa M., Ampapa R., Barnett M., Hughes S.E., Ramo-Tello C.M., Hodgkinson S., Spitaleri D.L.A., Petersen T., Butler E.G., Slee M., McGuigan C., McCombe P.A., Granella F., Cristiano E., Prevost J., Taylor B.V., Sa Nchez-Menoyo J.L., Laureys G., Van Hijfte L., Vucic S., Macdonell R.A., Gray O., Olascoaga J., Deri N., Fragoso Y.D., Shaw C., and Kalincik T.
- Abstract
BACKGROUND AND OBJECTIVES: The 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, ultraviolet B radiation exposure (UVB) and the severity of MS. METHOD(S): This 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 EDSS [Expanded Disability Status Scale] score recorded). The latitude of each study center and cumulative annualized UVB dose at study center (calculated from NASA's Total Ozone Mapping Spectrometer) at ages 6 and 18 and the year of disability assessment were calculated. Disease severity was quantified with MS Severity Score (MSSS). Quadratic regression was used to model the associations between latitude, UVB and MSSS. RESULT(S): 46,128 patients contributing 453,208 visits and a cumulative follow-up of 351,196 patient-years (70% women, mean age 39.2+/-12, resident between latitudes 19degree35' and 56degree16') were included in this study. Latitude showed a non-linear association with MS severity. In latitudes greater than 40degree, more severe disease was associated with higher latitudes (beta=0.08, 95%CI: 0.04 to 0.12). For example, this translates into a mean difference of 1.3 points of MSSS between patients living in Madrid and Copenhagen. No such association was observed in latitudes <40degree (beta=-0.02, 95% CI:-0.06 to 0.03). The overall disability accrual was faster in those with a lower level of estimated UVB exposure before the age of 6 (beta=- 0.5, 95% CI: -0.6 to 0.4) and 18 years (beta=- 0.6, 95%CI:-0.7 to 0.4), as well as with lower life-time UVB exposure at the time of disability assessment (be
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- 2022
26. Disease Reactivation After Cessation of Disease-Modifying Therapy in Patients With Relapsing-Remitting Multiple Sclerosis.
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Roos I., Malpas C., Leray E., Casey R., Horakova D., Havrdova E.K., Debouverie M., Patti F., De Seze J., Izquierdo G., Eichau S., Edan G., Prat A., Girard M., Ozakbas S., Grammond P., Zephir H., Ciron J., Maillart E., Moreau T., Amato M.P., Labauge P., Alroughani R., Buzzard K., Skibina O., Terzi M., Laplaud D.A., Berger E., Grand'Maison F., Lebrun-Frenay C., Cartechini E., Boz C., Lechner-Scott J., Clavelou P., Stankoff B., Prevost J., Kappos L., Pelletier J., Shaygannejad V., Yamout B.I., Khoury S.J., Gerlach O., Spitaleri D.L.A., Van Pesch V., Gout O., Turkoglu R., Heinzlef O., Thouvenot E., McCombe P.A., Soysal A., Bourre B., Slee M., Castillo-Trivino T., Bakchine S., Ampapa R., Butler E.G., Wahab A., Macdonell R.A., Aguera-Morales E., Cabre P., Ben N.H., Van der Walt A., Laureys G., Van Hijfte L., Ramo-Tello C.M., Maubeuge N., Hodgkinson S., Sanchez-Menoyo J.L., Barnett M.H., Labeyrie C., Vucic S., Sidhom Y., Gouider R., Csepany T., Sotoca J., de Gans K., Al-Asmi A., Fragoso Y.D., Vukusic S., Butzkueven H., Kalincik T., Roos I., Malpas C., Leray E., Casey R., Horakova D., Havrdova E.K., Debouverie M., Patti F., De Seze J., Izquierdo G., Eichau S., Edan G., Prat A., Girard M., Ozakbas S., Grammond P., Zephir H., Ciron J., Maillart E., Moreau T., Amato M.P., Labauge P., Alroughani R., Buzzard K., Skibina O., Terzi M., Laplaud D.A., Berger E., Grand'Maison F., Lebrun-Frenay C., Cartechini E., Boz C., Lechner-Scott J., Clavelou P., Stankoff B., Prevost J., Kappos L., Pelletier J., Shaygannejad V., Yamout B.I., Khoury S.J., Gerlach O., Spitaleri D.L.A., Van Pesch V., Gout O., Turkoglu R., Heinzlef O., Thouvenot E., McCombe P.A., Soysal A., Bourre B., Slee M., Castillo-Trivino T., Bakchine S., Ampapa R., Butler E.G., Wahab A., Macdonell R.A., Aguera-Morales E., Cabre P., Ben N.H., Van der Walt A., Laureys G., Van Hijfte L., Ramo-Tello C.M., Maubeuge N., Hodgkinson S., Sanchez-Menoyo J.L., Barnett M.H., Labeyrie C., Vucic S., Sidhom Y., Gouider R., Csepany T., Sotoca J., de Gans K., Al-Asmi A., Fragoso Y.D., Vukusic S., Butzkueven H., and Kalincik T.
- Abstract
OBJECTIVES: To evaluate the rate of return of disease activity after cessation of multiple sclerosis (MS) disease-modifying therapy. METHOD(S): This was a retrospective cohort study from two large observational MS registries: MSBase and OFSEP. Patients with relapsing-remitting MS who had ceased a disease-modifying therapy and were followed up for the subsequent 12-months were included in the analysis. The primary study outcome was annualised relapse rate in the 12 months after disease-modifying therapy discontinuation stratified by patients who did, and did not, commence a subsequent therapy. The secondary endpoint was the predictors of first relapse and disability accumulation after treatment discontinuation. RESULT(S): 14,213 patients, with 18,029 eligible treatment discontinuation epochs, were identified for seven therapies. Annualised rates of relapse (ARR) started to increase 2-months after natalizumab cessation (month 2-4 ARR, 95% confidence interval): 0.47, 0.43-0.51). Commencement of a subsequent therapy within 2-4 months reduced the magnitude of disease reactivation (mean ARR difference: 0.15, 0.08-0.22). After discontinuation of fingolimod, rates of relapse increased overall (month 1-2 ARR: 0.80, 0.70-0.89), and stabilised faster in patients who started a new therapy within 1-2 months (mean ARR difference: 0.14, -0.01-0.29). Magnitude of disease reactivation for other therapies was low, but reduced further by commencement of another treatment 1-10 months after treatment discontinuation. Predictors of relapse were higher relapse rate in the year before cessation, female sex, younger age and higher EDSS. Commencement of a subsequent therapy reduced both the risk of relapse (HR 0.76, 95%CI 0.72-0.81) and disability accumulation (0.73, 0.65-0.80). CONCLUSION(S): The rate of disease reactivation after treatment cessation differs among MS treatments, with the peaks of relapse activity ranging from 1 to 10 months in untreated cohorts that discontinued different t
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- 2022
27. Disease Reactivation After Cessation of Disease-Modifying Therapy in Patients With Relapsing-Remitting Multiple Sclerosis
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Roos, I, Malpas, C, Leray, E, Casey, R, Horakova, D, Havrdova, EK, Debouverie, M, Patti, F, De Seze, J, Izquierdo, G, Eichau, S, Edan, G, Prat, A, Girard, M, Ozakbas, S, Grammond, P, Zephir, H, Ciron, J, Maillart, E, Moreau, T, Amato, MP, Labauge, P, Alroughani, R, Buzzard, K, Skibina, O, Terzi, M, Laplaud, DA, Berger, E, Grand'Maison, F, Lebrun-Frenay, C, Cartechini, E, Boz, C, Lechner-Scott, J, Clavelou, P, Stankoff, B, Prevost, J, Kappos, L, Pelletier, J, Shaygannejad, V, Yamout, B, Khoury, SJ, Gerlach, O, Spitaleri, DLA, Van Pesch, V, Gout, O, Turkoglu, R, Heinzlef, O, Thouvenot, E, McCombe, PA, Soysal, A, Bourre, B, Slee, M, Castillo-Trivino, T, Bakchine, S, Ampapa, R, Butler, EG, Wahab, A, Macdonell, RA, Aguera-Morales, E, Cabre, P, Ben, NH, Van der Walt, A, Laureys, G, Van Hijfte, L, Ramo-Tello, CM, Maubeuge, N, Hodgkinson, S, Sanchez-Menoyo, JL, Barnett, MH, Labeyrie, C, Vucic, S, Sidhom, Y, Gouider, R, Csepany, T, Sotoca, J, de Gans, K, Al-Asmi, A, Fragoso, YD, Vukusic, S, Butzkueven, H, Kalincik, T, Roos, I, Malpas, C, Leray, E, Casey, R, Horakova, D, Havrdova, EK, Debouverie, M, Patti, F, De Seze, J, Izquierdo, G, Eichau, S, Edan, G, Prat, A, Girard, M, Ozakbas, S, Grammond, P, Zephir, H, Ciron, J, Maillart, E, Moreau, T, Amato, MP, Labauge, P, Alroughani, R, Buzzard, K, Skibina, O, Terzi, M, Laplaud, DA, Berger, E, Grand'Maison, F, Lebrun-Frenay, C, Cartechini, E, Boz, C, Lechner-Scott, J, Clavelou, P, Stankoff, B, Prevost, J, Kappos, L, Pelletier, J, Shaygannejad, V, Yamout, B, Khoury, SJ, Gerlach, O, Spitaleri, DLA, Van Pesch, V, Gout, O, Turkoglu, R, Heinzlef, O, Thouvenot, E, McCombe, PA, Soysal, A, Bourre, B, Slee, M, Castillo-Trivino, T, Bakchine, S, Ampapa, R, Butler, EG, Wahab, A, Macdonell, RA, Aguera-Morales, E, Cabre, P, Ben, NH, Van der Walt, A, Laureys, G, Van Hijfte, L, Ramo-Tello, CM, Maubeuge, N, Hodgkinson, S, Sanchez-Menoyo, JL, Barnett, MH, Labeyrie, C, Vucic, S, Sidhom, Y, Gouider, R, Csepany, T, Sotoca, J, de Gans, K, Al-Asmi, A, Fragoso, YD, Vukusic, S, Butzkueven, H, and Kalincik, T
- Abstract
BACKGROUND AND OBJECTIVES: To evaluate the rate of return of disease activity after cessation of multiple sclerosis (MS) disease-modifying therapy. METHODS: This was a retrospective cohort study from 2 large observational MS registries: MSBase and OFSEP. Patients with relapsing-remitting MS who had ceased a disease-modifying therapy and were followed up for the subsequent 12 months were included in the analysis. The primary study outcome was annualized relapse rate in the 12 months after disease-modifying therapy discontinuation stratified by patients who did, and did not, commence a subsequent therapy. The secondary endpoint was the predictors of first relapse and disability accumulation after treatment discontinuation. RESULTS: A total of 14,213 patients, with 18,029 eligible treatment discontinuation epochs, were identified for 7 therapies. Annualized rates of relapse (ARRs) started to increase 2 months after natalizumab cessation (month 2-4 ARR 0.47, 95% CI 0.43-0.51). Commencement of a subsequent therapy within 2-4 months reduced the magnitude of disease reactivation (mean ARR difference: 0.15, 0.08-0.22). After discontinuation of fingolimod, rates of relapse increased overall (month 1-2 ARR: 0.80, 0.70-0.89) and stabilized faster in patients who started a new therapy within 1-2 months (mean ARR difference: 0.14, -0.01 to 0.29). The magnitude of disease reactivation for other therapies was low but reduced further by commencement of another treatment 1-10 months after treatment discontinuation. Predictors of relapse were a higher relapse rate in the year before cessation, female sex, younger age, and higher EDSS score. Commencement of a subsequent therapy reduced both the risk of relapse (HR 0.76, 95% CI 0.72-0.81) and disability accumulation (0.73, 0.65-0.80). DISCUSSION: The rate of disease reactivation after treatment cessation differs among MS treatments, with the peaks of relapse activity ranging from 1 to 10 months in untreated cohorts that discontinued di
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- 2022
28. Comparative effectiveness of cladribine tablets versus other oral disease-modifying treatments for multiple sclerosis: results from MSBase registry
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Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Spelman, T.; Ozakbas, S.; Alroughani, R.; Terzi, M.; Hodgkinson, S.; Laureys, G.; Kalincik, T.; Van Der Walt, A.; Yamout, B.; Lechner-Scott, J.; Soysal, A.; Kuhle, J.; Sanchez-Menoyo, J.L.; Blanco Morgado, Y.; Spitaleri, D.; van Pesch, V.; Horakova, D.; Ampapa, R.; Patti, F.; Macdonell, R.; Al-Asmi, A.; Gerlach, O.; Oh, J.; Tundia, N.; Wong, S.L.; Butzkueven, H., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine, Altıntaş, Ayşe (ORCID 0000-0002-8524-5087 & YÖK ID 11611), Spelman, T.; Ozakbas, S.; Alroughani, R.; Terzi, M.; Hodgkinson, S.; Laureys, G.; Kalincik, T.; Van Der Walt, A.; Yamout, B.; Lechner-Scott, J.; Soysal, A.; Kuhle, J.; Sanchez-Menoyo, J.L.; Blanco Morgado, Y.; Spitaleri, D.; van Pesch, V.; Horakova, D.; Ampapa, R.; Patti, F.; Macdonell, R.; Al-Asmi, A.; Gerlach, O.; Oh, J.; Tundia, N.; Wong, S.L.; Butzkueven, H., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), and School of Medicine
- Abstract
Background: effectiveness of cladribine tablets, an oral disease-modifying treatment (DMT) for multiple sclerosis (MS), was established in clinical trials and confirmed with real-world experience. Objectives: use real-world data to compare treatment patterns and clinical outcomes in people with MS (pwMS) treated with cladribine tablets versus other oral DMTs. Methods: retrospective treatment comparisons were based on data from the international MSBase registry. Eligible pwMS started treatment with cladribine, fingolimod, dimethyl fumarate, or teriflunomide tablets from 2018 to mid-2021 and were censored at treatment discontinuation/switch, death, loss to follow-up, pregnancy, or study period end. Treatment persistence was evaluated as time to discontinuation/switch; relapse outcomes included time to first relapse and annualized relapse rate (ARR). Results: cohorts included 633 pwMS receiving cladribine tablets, 1195 receiving fingolimod, 912 receiving dimethyl fumarate, and 735 receiving teriflunomide. Individuals treated with fingolimod, dimethyl fumarate, or teriflunomide switched treatment significantly more quickly than matched cladribine tablet cohorts (adjusted hazard ratio (95% confidence interval): 4.00 (2.54-6.32), 7.04 (4.16-11.93), and 6.52 (3.79-11.22), respectively). Cladribine tablet cohorts had significantly longer time-to-treatment discontinuation, time to first relapse, and lower ARR, compared with other oral DMT cohorts. Conclusion: cladribine tablets were associated with a significantly greater real-world treatment persistence and more favorable relapse outcomes than all oral DMT comparators., Financial support for this study was provided entirely by a contract with EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA (CrossRef Funder ID: 10.13039/100004755). The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report. The following authors are employed by the sponsor: NT and SLW.
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- 2022
29. Real-world experience with ocrelizumab in relapsing multiple sclerosis: insights from the MSOCR-R cohort, an MSBase registry sub-study
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Sotoca, J., Rojas, J. I., Sanchez Menoyo, J. L., Kermode, A., Barnett, M., Grand'Maison, F., Van Pesch, V., Terzi, M., Van Hijfte, L., Laureys, G., Alroughani, R., van der Walt, A., Kalincik, T., Skibina, O., Buzzard, K., Boz, C., Spelman, T., Butzkueven, H., Ozakbas, SERKAN, Lechner-Scott, J., Muros-Le Rouzic, E., Liu, C., Dirks, P., and Skromne, E.
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- 2021
30. Real-world experience with cladribine in the MSBase Registry
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Prevost, J., Van der Walt, A., Kalincik, T., Grand-Maison, F., McCombe, P., Butler, E., Lechner-Scott, J., di Cantogno, E. Verdun, Van Hijfte, L., Laureys, G., Ozakbas, SERKAN, Girard, M., Prat, A., Hodgkinson, S., Spelman, T., Butzkueven, H., Van Pesch, V., Macdonell, R., Oh, J., Alroughani, R., Grammond, P., Sanchez-Menoyo, J. -L., Terzi, M., Duquette, P., Madueno, S. Eichau, Izquierdo, G., Buzzard, K., and Skabina, O.
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- 2021
31. Real-world experience with ocrelizumab in the msbase registry.
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Hodgkinson S., Spelman T., Ozakbas S., Kalincik T., Boz C., Buzzard K., Skibina O., Alroughani R., Karabudak R., Van Der Walt A., Lechner-Scott J., Taylor B., Kermode A., Mccombe P., Duquette P., Prat A., Girard M., Eichau Madueno S., Izquierdo G., Soysal A., Sanchez-Menoyo J.L., Sotoca J., Muros-Le Rouzic E., Dirks P., Butzkueven H., Laureys G., Van Hijfte L., Terzi M., Butler E., Macdonell R., Patti F., Van Pesch V., Slee M., Barnett M., Grammond P., Prevost J., Grand-Maison F., Hodgkinson S., Spelman T., Ozakbas S., Kalincik T., Boz C., Buzzard K., Skibina O., Alroughani R., Karabudak R., Van Der Walt A., Lechner-Scott J., Taylor B., Kermode A., Mccombe P., Duquette P., Prat A., Girard M., Eichau Madueno S., Izquierdo G., Soysal A., Sanchez-Menoyo J.L., Sotoca J., Muros-Le Rouzic E., Dirks P., Butzkueven H., Laureys G., Van Hijfte L., Terzi M., Butler E., Macdonell R., Patti F., Van Pesch V., Slee M., Barnett M., Grammond P., Prevost J., and Grand-Maison F.
- Abstract
Background: Ocrelizumab (OCR) is a humanised anti-CD20+ monoclonal antibody approved for the treatment of primary progressive multiple sclerosis (PPMS), and relapsing forms of MS, including both relapsing-remitting (RRMS) and secondary progressive MS (SPMS) with relapses. Objective(s): In a real-world setting, to describe 1) baseline characteristics of patients with MS treated with OCR, 2) treatment pathway across lines of therapy up to initiation of OCR, and 3) initial clinical experience in patients with >=6 months follow-up data from OCR initiation. Method(s): Secondary data analysis using MSBase Registry data including patients with a confirmed diagnosis of MS and started OCR therapy within 3 months prior to or at time of MSBase eligible/ initial visit. Descriptive statistics were used to analyze baseline patient characteristics' recorded within 3 months of OCR initiation, including demographics, disease course and duration, prior disease modifying therapies (DMT), and EDSS. Occurrence of relapse was analyzed in patients with >=6 months follow-up data from OCR initiation. Result(s): As of 4th June 2020, MSBase included 2531 patients newly treated with OCR, of whom 1679 had an EDSS evaluation within 3 months of OCR start. There were 1185 patients with RRMS, 236 with SPMS, and 183 with PPMS. Median age at OCR initiation was 41.9 years, 49.5 years, to 50.1 years in RRMS, SPMS, and PPMS, respectively. Mean disease duration from symptom onset up to OCR initiation was longer in SPMS (19.7 years) than in RRMS (10.6 years) and PPMS (9.7 years). OCR was initiated as first line therapy in 17.5%, 5.5%, and 54.2% of RRMS, SPMS, and PPMS patients respectively. Most frequent previous DMT's in RRMS were fingolimod (25.7%) and natalizumab (23.5%). 693 patients with RRMS had >=6 months followup during OCR exposure. Of these, 643 remained relapse free (93%; 95% CI 86.0, 100.0) over a mean OCR exposure of 1.23 years. The annualized relapse rate (ARR) was 0.08 (95% CI 0.06- 0.10)
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- 2021
32. Prediction of multiple sclerosis outcomes when switching to ocrelizumab.
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Zhong M., van der Walt A., Stankovich J., Kalincik T., Buzzard K., Skibina O., Boz C., Hodgkinson S., Slee M., Lechner-Scott J., Macdonell R., Prevost J., Kuhle J., Laureys G., Van Hijfte L., Alroughani R., Kermode A.G., Butler E., Barnett M., Eichau S., van Pesch V., Grammond P., McCombe P., Karabudak R., Duquette P., Girard M., Taylor B., Yeh W., Monif M., Gresle M., Butzkueven H., Jokubaitis V.G., Zhong M., van der Walt A., Stankovich J., Kalincik T., Buzzard K., Skibina O., Boz C., Hodgkinson S., Slee M., Lechner-Scott J., Macdonell R., Prevost J., Kuhle J., Laureys G., Van Hijfte L., Alroughani R., Kermode A.G., Butler E., Barnett M., Eichau S., van Pesch V., Grammond P., McCombe P., Karabudak R., Duquette P., Girard M., Taylor B., Yeh W., Monif M., Gresle M., Butzkueven H., and Jokubaitis V.G.
- Abstract
Background: Increasingly, people with relapsing-remitting multiple sclerosis (RRMS) are switched to highly effective disease-modifying therapies (DMTs) such as ocrelizumab. Objective(s): To determine predictors of relapse and disability progression when switching from another DMT to ocrelizumab. Method(s): Patients with RRMS who switched to ocrelizumab were identified from the MSBase Registry and grouped by prior disease-modifying therapy (pDMT; interferon-beta/glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod or natalizumab) and washout duration (<1 month, 1-2 months or 2-6 months). Survival analyses including multivariable Cox proportional hazard regression models were used to identify predictors of on-ocrelizumab relapse within 1 year, and 6-month confirmed disability progression (CDP). Result(s): After adjustment, relapse hazard when switching from fingolimod was greater than other pDMTs, but only in the first 3 months of ocrelizumab therapy (hazard ratio (HR) = 3.98, 95% confidence interval (CI) = 1.57-11.11, p = 0.004). The adjusted hazard for CDP was significantly higher with longer washout (2-6 m compared to <1 m: HR = 9.57, 95% CI = 1.92-47.64, p = 0.006). Conclusion(s): The risk of disability worsening during switch to ocrelizumab is reduced by short treatment gaps. Patients who cease fingolimod are at heightened relapse risk in the first 3 months on ocrelizumab. Prospective evaluation of strategies such as washout reduction may help optimise this switch.Copyright © The Author(s), 2021.
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- 2021
33. Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis.
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Van Pesch V., 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., 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 L.G.F., Sanchez-Menoyo J.L., 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., Kalincik T., Diouf I., Malpas C., Horakova D., Kubala Havrdova E., Patti F., Shaygannejad V., Ozakbas S., Izquierdo G., Van Pesch V., 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., 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 L.G.F., Sanchez-Menoyo J.L., 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., Kalincik T., Diouf I., Malpas C., Horakova D., Kubala Havrdova E., Patti F., Shaygannejad V., Ozakbas S., and Izquierdo G.
- Abstract
Background: Our current understanding of demographic and clinical modifiers of the effectiveness of multiple sclerosis (MS) therapies is limited. Objective(s): To assess whether patients' response to disease modifying therapies (DMT) in MS varies by disease activity (annualised relapse rate, presence of new MRI lesions), disability, age, MS duration or disease phenotype. Method(s): Using the international MSBase registry, we selected patients with MS followed for >=1 year, with >=3 visits, >=1 visit per year. Marginal structural models (MSMs) were used to compare the hazard ratios (HR) of 6-month confirmed worsening and improvement of disability (EDSS), and the incidence of relapses between treated and untreated periods. MSMs were continuously re-adjusted for patient age, sex, pregnancy, date, time from first symptom, prior relapse history, disability and MRI activity. Result(s): Among 23 687 patients with relapsing MS, those on DMT experienced 20% greater chance of disability improvement [HR 1.20 (95% CI 1.0-1.5)], 47% lower risk of disability worsening [HR 0.53 (0.39-0.71)] and 51% reduction in relapses [HR 0.49 (0.43-0.55)]. The effect of DMT on relapses and EDSS worsening was attenuated with longer MS duration and higher prior relapse rate. The effect of DMT on EDSS improvement and relapses was more evident in low EDSS categories. DMT was associated with 51% EDSS improvement in patients without new MRI lesions [HR 1.51 (1.00-2.28)] compared to 4% in those with MRI activity [HR 1.04 (0.88-1.24)]. Among 26329 participants with relapsing or progressive MS, DMT was associated with 25% reduction in EDSS worsening and 42% reduction in relapses in patients with relapsing MS [HR 0.75 (0.65-0.86) and HR 0.58 (CI 0.54-62), respectively], while evidence for such beneficial effects of treatment in patients with progressive MS was not found [HR 1.11 (0.91-1.46) and HR 1.16 (0.91-1.46), respectively]. Conclusion(s): DMTs are associated with reduction in relapse frequency, pro
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- 2021
34. Comparison of the effectiveness of ocrelizumab vs interferons, fingolimod and natalizumab on relapses in relapsing-remitting multiple sclerosis.
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Roos I., Sharmin S., Ozakbas S., Horakova D., Havrdova E.K., Boz C., Alroughani R., Patti F., Terzi M., Lechner-Scott J., Izquierdo G., Eichau S., Grammond P., Buzzard K., Skibina O., Prat A., Girard M., Duquette P., Soysal A., Grand'Maison F., Kuhle J., Van Der Walt A., Butzkueven H., Turkoglu R., Butler E., Laureys G., Van Hijfte L., Shaygannejad V., Yamout B., Khoury S., Prevost J., Sidhom Y., Gouider R., Cartechini E., Sanchez-Menoyo J.L., Jose Sa M., Macdonell R., Van Pesch V., Ramo-Tello C., McCombe P., Willekens B., Spitaleri D., Ampapa R., Al-Asmi A., Slee M., Besora S., Malpas C., Kalincik T., Roos I., Sharmin S., Ozakbas S., Horakova D., Havrdova E.K., Boz C., Alroughani R., Patti F., Terzi M., Lechner-Scott J., Izquierdo G., Eichau S., Grammond P., Buzzard K., Skibina O., Prat A., Girard M., Duquette P., Soysal A., Grand'Maison F., Kuhle J., Van Der Walt A., Butzkueven H., Turkoglu R., Butler E., Laureys G., Van Hijfte L., Shaygannejad V., Yamout B., Khoury S., Prevost J., Sidhom Y., Gouider R., Cartechini E., Sanchez-Menoyo J.L., Jose Sa M., Macdonell R., Van Pesch V., Ramo-Tello C., McCombe P., Willekens B., Spitaleri D., Ampapa R., Al-Asmi A., Slee M., Besora S., Malpas C., and Kalincik T.
- Abstract
Introduction: Ocrelizumab, a monoclonal antibody targeted against CD20+ B cells, has become a popular treatment for relapsing-remitting multiple sclerosis (MS). The effectiveness of ocrelizumab compared to other treatments is however unknown. Aim(s): To compare the effectiveness of ocrelizumab with interferon-beta, fingolimod and natalizumab in relapsing-remitting MS. Method(s): Using the MSBase registry, we identified patients with relapsing-remitting MS treated for >=6 months with ocrelizumab, interferon- beta (interferon beta-1a, interferon beta-1b subcutaneous or interferon beta-1b intramuscular), fingolimod or natalizumab. All patients required >12-month pre-treatment follow up and the minimum dataset. Patients with comparable baseline characteristics were matched with propensity score on age, sex, MS duration, EDSS, prior relapse rate, prior therapy, disease activity, MRI lesion burden (missing values imputed), reason for discontinuation of preceding therapy (imputed) and country. Annualised rate of relapses (ARR) and cumulative hazard of relapses were compared in pairwise-censored groups. Result(s): 106 patients treated with ocrelizumab were matched with 209 patients on interferon therapies with a mean age of 39 years, 0.8 relapses per year and mean EDSS of 2.4-2.5. Over a pairwise-censored mean follow up of 1.3 years, ocrelizumab was associated with lower relapse rates (ARR 0.08 vs 0.27, p<0.001) and lower risk of relapse (HR 0.30, 95%CI 0.15-0.57) than interferon-beta. 297 patients treated with ocrelizumab were matched with 811 fingolimod-treated patients with a mean age of 41 years, 0.6 relapses per year and mean EDSS of 2.7-2.8. Over a pairwisecensored mean follow up of 1.5 years, ocrelizumab was associated with lower relapse rates (ARR 0.03 vs 0.14, p<0.001) and lower risk of relapse than fingolimod (HR 0.21, 0.13-0.32). 262 ocrelizumab- treated patients were matched with 343 natalizumab treated patients with a mean age of 39 years, 0.8 relapses per year
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- 2021
35. Variability of the Response to Immunotherapy among Sub-groups of Patients with Multiple Sclerosis.
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Diouf I., Malpas C., Horakova D., Havrdova E., Patti F., Shaygannejad V., Ozakbas S., Ayuso G.I., Madueno S.E., Zakaria M., Onofrj M., Lugaresi A., Alroughani R., Prat A., Girard M., Duquette P., Terzi M., Cavit B., GrandaMaison F., Hamdy S., Sola P., Ferraro D., Grammond P., Turkoglu R., Butzkueven H., Yamout B., Altintas A., VanPesch V., Maimone D., Lechner-Scott J., Bergamaschi R., Karabudak R., Iuliano G., McGuigan C., Cartechini E., Barnett M., Hughes S., Sa M.J., Kappos L., Ramo-Tello C., Cristiano E., Hodgkinson S., Spitaleri D.L.A., Soysal A., Petersen T., Slee M., Butler E., Granella F., Verheul F., McCombe P., Ampapa R., Skibina O., Prevost J., Sinnige L., Sanchez-Menoyo J.L., Vucic S., Laureys G., VanHijfte L., Khurana D., MacDonell R., Castillo-Trivino T., Gray O., Aguera-Morales E., Kister I., Shaw C., Deri N., Al-Harbi T., Fragoso Y., Csepany T., Sempere A., Kalincik T., Diouf I., Malpas C., Horakova D., Havrdova E., Patti F., Shaygannejad V., Ozakbas S., Ayuso G.I., Madueno S.E., Zakaria M., Onofrj M., Lugaresi A., Alroughani R., Prat A., Girard M., Duquette P., Terzi M., Cavit B., GrandaMaison F., Hamdy S., Sola P., Ferraro D., Grammond P., Turkoglu R., Butzkueven H., Yamout B., Altintas A., VanPesch V., Maimone D., Lechner-Scott J., Bergamaschi R., Karabudak R., Iuliano G., McGuigan C., Cartechini E., Barnett M., Hughes S., Sa M.J., Kappos L., Ramo-Tello C., Cristiano E., Hodgkinson S., Spitaleri D.L.A., Soysal A., Petersen T., Slee M., Butler E., Granella F., Verheul F., McCombe P., Ampapa R., Skibina O., Prevost J., Sinnige L., Sanchez-Menoyo J.L., Vucic S., Laureys G., VanHijfte L., Khurana D., MacDonell R., Castillo-Trivino T., Gray O., Aguera-Morales E., Kister I., Shaw C., Deri N., Al-Harbi T., Fragoso Y., Csepany T., Sempere A., and Kalincik T.
- Abstract
Objective: To assess whether patients' response to disease modifying therapies (DMT) in multiple sclerosis (MS) varies by disease activity (annualised relapse rate, presence of new MRI lesions), disability, age, MS duration or disease phenotype. Background(s): Our understanding of demographic and clinical modifiers of the effectiveness of MS therapies is limited. Design/Methods: Using the international MSBase registry, we selected patients with MS followed for >=1 year, with >=3 visits, >=1 visit per year. Marginal structural models were used to compare the hazard ratios (HR) of 6-month confirmed worsening and improvement of disability (EDSS), and the incidence of relapses between treated and untreated periods. Models were continuously re-adjusted for patient age, sex, pregnancy, date, time from first symptom, prior relapse history, disability and MRI activity. Result(s): Among 23687 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence [HR=0.52 (0.44-0.61)], 48% lower risk of disability worsening [HR=0.52 (0.38-0.71)] and 33% greater chance of disability improvement [HR=1.33 (95%CI 1.0-1.5)]. The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The effect of DMTs on reducing relapses declined with higher prior relapse rate and in patients with prior cerebral MRI activity. Among 26329 participants with relapsing or progressive MS, DMTs were associated with 25% reduction in EDSS worsening and 42% reduction in relapses in patients with relapsing MS [HR=0.75 (0.65-0.86) and HR=0.58 (0.54-62), respectively], while evidence for such beneficial effects of treatment in patients with progressive MS was not found [HR=1.11 (0.91-1.46) and HR=1.16 (0.91-1.46), respectively]. Conclusion(s): DMTs are associated with reduction in relapse frequency, progression of disability, and increased chance of recovery from disability. The DMTs are most effective among patients with lower
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- 2021
36. Association of latitude and exposure to ultraviolet B radiation with severity of multiple sclerosis.
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Vitkova M., Diouf I., Malpas C., Horakova D., Havrdova E.K., Patti F., Ozakbas S., Ayuso G.I., Madueno S.E., Shaygannejad V., Onofrj M., Lugaresi A., Alroughani R., Prat A., Larochelle C., Girard M., Duquette P., Terzi M., Boz C., GrandaMaison F., Sola P., Ferraro D., Grammond P., Butzkueven H., Buzzard K., Skibina O., Yamout B., Karabudak R., Gerlach O.H.H., Lechner-Scott J., Maimone D., Bergamaschi R., VanPesch V., Iuliano G., Cartechini E., Sa M.J., Ampapa R., Barnett M., Hughes S., Ramo-Tello C., Hodgkinson S., Spitareli D., Petersen T., Butler E., Slee M., McGuigan C., McCombe P., Granella F., Cristiano E., Prevost J., Taylor B., Sanchez-Menoyo J.L., Laureys G., VanHijfte L., Vucic S., MacDonell R., Gray O., Urtaza F.J.O., Deri N., Fragoso Y., Shaw C., Kalincik T., Vitkova M., Diouf I., Malpas C., Horakova D., Havrdova E.K., Patti F., Ozakbas S., Ayuso G.I., Madueno S.E., Shaygannejad V., Onofrj M., Lugaresi A., Alroughani R., Prat A., Larochelle C., Girard M., Duquette P., Terzi M., Boz C., GrandaMaison F., Sola P., Ferraro D., Grammond P., Butzkueven H., Buzzard K., Skibina O., Yamout B., Karabudak R., Gerlach O.H.H., Lechner-Scott J., Maimone D., Bergamaschi R., VanPesch V., Iuliano G., Cartechini E., Sa M.J., Ampapa R., Barnett M., Hughes S., Ramo-Tello C., Hodgkinson S., Spitareli D., Petersen T., Butler E., Slee M., McGuigan C., McCombe P., Granella F., Cristiano E., Prevost J., Taylor B., Sanchez-Menoyo J.L., Laureys G., VanHijfte L., Vucic S., MacDonell R., Gray O., Urtaza F.J.O., Deri N., Fragoso Y., Shaw C., and Kalincik T.
- Abstract
Objective: The aim of this study was to investigate the association between latitude of residence, ultraviolet B radiation exposure (UVB) and the severity of multiple sclerosis (MS). Background(s): Severity of (MS) varies widely among individuals. Understanding of determinants of this heterogeneity will help clinicians optimize the management of MS in individual patients. Design/Methods: This observational study used the global MSBase registry. Disease severity was quantified with MS Severity Score (MSSS, a decile of disability relative to a normative cohort with similar disease duration). The latitude of each study center (stratified by hemisphere) and cumulative annualized UVB dose at study center (calculated from from NASA's Total Ozone Mapping Spectrometer) at ages 6 and 18 and the year of disability assessment were calculated. Quadratic regression was used to model the associations between latitude, UVB and MSSS. Result(s): 46,128 patients (70% women, mean age 39+/-12, resident between latitudes 19degree35' and 56degree16', cumulative follow-up 351,196 patient-years) were included. Latitude showed a non-linear association with MS severity. Above 40degree of latitude, more severe disease was associated with higher latitudes (beta= 0.08, 95%CI: 0.04, 0.12). For example, this translates into a mean difference of 1.3 points of MSSS between patients living in Madrid and Copenhagen. No such association was observed in latitudes <40degree (beta= 0.02, 95%CI: 0.06, 0.03). The overall disability accrual was faster in those with a lower level of estimated UVB exposure before the age of 6 (beta= 0.5, 95%CI: 0.6, 0.4) and 18 years (beta= 0.6, 95%CI: 0.7, 0.4) as well as with lower life-time UVB exposure at the time of disability assessment (beta= 1.0, 95%CI: 1.1, 0.9). Conclusion(s): In temperate zones, MS severity is associated with latitude. This association is mainly, but not exclusively, driven by UVB exposure. Thus, UVB exposure contributes to both MS susceptibility a
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- 2021
37. Disability accrual in primary-progressive & secondaryprogressive multiple sclerosis.
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Boz C., Diouf I., Malpas C., Nguyen A.-L., Moradi N., Horakova D., Kubala Havrdova E., Patti F., Izquierdo G., Eichau S., Prat A., Girard M., Duquette P., Onofrj M., Lugaresi A., Grand'Maison F., Weinstock-Guttman B., Amato M.P., Grammond P., Gerlach O., Ozakbas S., Sola P., Ferraro D., Butzkueven H., Lechner-Scott J., Alroughani R., Van Pesch V., Cartechini E., Terzi M., Maimone D., Ramo-Tello C., Spitaleri D., Kappos L., Yamout B., Sa M., Slee M., Blanco Y., Bergamaschi R., Butler E., Iuliano G., Granella F., Sidhom Y., Gouider R., Ampapa R., Van Wijmeersch B., Karabudak R., Prevost J., Sanchez-Menoyo J.L., Verheul F., Mccombe P., Castillo-Trivino T., Macdonell R., Altintas A., Laureys G., Van Hijfte L., Van Der Walt A., Vucic S., Turkoglu R., Barnett M., Cristiano E., Zakaria M., Shaygannejad V., Hodgkinson S., Soysal A., Kalincik T., Harding-Forrester S., Roos I., Sharmin S., Boz C., Diouf I., Malpas C., Nguyen A.-L., Moradi N., Horakova D., Kubala Havrdova E., Patti F., Izquierdo G., Eichau S., Prat A., Girard M., Duquette P., Onofrj M., Lugaresi A., Grand'Maison F., Weinstock-Guttman B., Amato M.P., Grammond P., Gerlach O., Ozakbas S., Sola P., Ferraro D., Butzkueven H., Lechner-Scott J., Alroughani R., Van Pesch V., Cartechini E., Terzi M., Maimone D., Ramo-Tello C., Spitaleri D., Kappos L., Yamout B., Sa M., Slee M., Blanco Y., Bergamaschi R., Butler E., Iuliano G., Granella F., Sidhom Y., Gouider R., Ampapa R., Van Wijmeersch B., Karabudak R., Prevost J., Sanchez-Menoyo J.L., Verheul F., Mccombe P., Castillo-Trivino T., Macdonell R., Altintas A., Laureys G., Van Hijfte L., Van Der Walt A., Vucic S., Turkoglu R., Barnett M., Cristiano E., Zakaria M., Shaygannejad V., Hodgkinson S., Soysal A., Kalincik T., Harding-Forrester S., Roos I., and Sharmin S.
- Abstract
Background: Some cohort studies have reported similar onset age and disability accrual in primary and secondary progressive MS (PPMS, SPMS); others have reported later onset and faster disability accrual in SPMS. Comparisons are complicated by differences in baseline disability and exposure to disease-modifying therapies (DMT), and by lack of a standardized definition of SPMS. Objective(s): We compared hazards of disability accrual in PPMS and SPMS patients from the MSBase cohort using multivariable Cox models, applying validated diagnostic criteria for SPMS (Lorscheider et al., Brain 2016). Method(s): Inclusion required adult-onset progressive MS; >= 3 recorded Expanded Disability Status Scale (EDSS) scores; and, for SPMS, initial records with EDSS <= 3 to allow objective identification of SPMS conversion. Phenotypes were subgrouped as active (PPMS-A, SPMS-A) if >= 1 progressive-phase relapse was recorded, and inactive (PPMS-N, SPMS-N) otherwise. Disability accrual was defined by sustained EDSS increases confirmed over >= 6 months. Hazard ratios (HR) for disability accrual were obtained using Andersen-Gill Cox models, adjusted for sex and time-varying age, disability, visit frequency, and proportion of time on DMT or immunosuppressive therapy. Sensitivity analyses were performed using (1) PPMS and SPMS diagnosed since 1995, and (2) physician-diagnosed SPMS. Cumulative probability of reaching EDSS >= 7 (wheelchair required) was assessed (Kaplan-Meier). Result(s): 5461 patients were included (1257 PPMS-N; 1308 PPMS-A; 1731 SPMS-N; 1165 SPMS-A). Age at progression onset was older in SPMS than PPMS (47.2 +/- 10.2, vs. 41.5 +/- 10.7 [mean +/- SD]), and in the inactive subgroups of each phenotype. Hazard of disability accrual was decreased in SPMS relative to PPMS (HR 0.85; 95% CI 0.78-0.92); decreased by proportion of time on DMT (HR 0.99 per 10% increment; 0.98-0.99); and higher in males (1.18; 1.12-1.25). Relative to PPMS-N, hazard was decreased in SPMS-A (0.79; 0.71
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- 2021
38. Real-world experience with cladribine in the MSBase Registry.
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Butzkueven H., Spelman T., Hodgkinson S., Eichau Madueno S., Izquierdo G., Buzzard K., Skabina O., Van Der Walt A., Kalincik T., Grand-Maison F., McCombe P., Butler E., Prevost J., Van Pesch V., Ozakbas S., Macdonell R., Oh J., Alroughani R., Lechner-Scott J., Grammond P., Sanchez-Menoyo J.-L., Terzi M., Duquette P., Prat A., Girard M., Laureys G., Van Hijfte L., Verdun Di Cantogno E., Butzkueven H., Spelman T., Hodgkinson S., Eichau Madueno S., Izquierdo G., Buzzard K., Skabina O., Van Der Walt A., Kalincik T., Grand-Maison F., McCombe P., Butler E., Prevost J., Van Pesch V., Ozakbas S., Macdonell R., Oh J., Alroughani R., Lechner-Scott J., Grammond P., Sanchez-Menoyo J.-L., Terzi M., Duquette P., Prat A., Girard M., Laureys G., Van Hijfte L., and Verdun Di Cantogno E.
- Abstract
Introduction: Cladribine tablets are approved for relapsing multiple sclerosis (RMS) treatment in many jurisdictions. MSBase investigators are committed to characterising real-world longitudinal treatment outcomes using this registry data. Objective(s): To describe cladribine treatment outcomes in the MSBase cohort. These include baseline characteristics, treatment pathways, discontinuation rate, and relapse outcomes. Method(s): We extracted from the MSBase registry data for all patients with a confirmed diagnosis of MS who were newly treated with cladribine tablets. Descriptive statistics were used to analyse baseline patient characteristics recorded within 3 months prior to cladribine tablets initiation, including demographics, disease course and duration, prior disease modifying drugs (DMD), and EDSS. Relapse and discontinuation outcomes were described in patients with a minimum 6 month observation period. Result(s): As of 3rd March 2021, a total of 782 patients, predominantly from Australia, Canada and Spain, were included. 696 were relapsing-remitting MS (RRMS) patients. The median age of cladribine tablet start was 43.8 years and median disease duration was 11.8 years. Median EDSS at cladribine initiation was 2 (IQR 1.5,4). 13.3% of all RRMS patients initiated cladribine as first line therapy. Of all RRMS patients switching to cladribine tablets with a treatment gap of <6 months, the most common immediate prior DMD was Fingolimod (15%), followed by Natalizumab (10%) and Teriflunomide (9.5%). Total follow-up time was 629 patientyears. Annualised relapse rate (ARR) on cladribine tablets was 0.11 (95% CI 0.09-0.14) compared to a 12-month pre-cladribine ARR of 0.41. Treatment persistence was 96% at 12 months (95% CI 0.94-0.98) and 90% after 24months (95% CI 0.85-0.94). Conclusion(s): The growing MSBase real-world cladribine cohort shows excellent outcomes to date. The most common switches to cladribine are from other high-efficacy DMTs such as Natalizumab or Fingo
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- 2021
39. Off-label drug use in paediatric haemato-oncology patients: financial implications and proposed solutions for Belgian patients.
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UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Centre de malformations vasculaires congénitales, UCL - (SLuc) Service d'hématologie et d'oncologie pédiatrique, Bauters, T, Heenen, D, Norga, K, Van Damme, A, Uyttebroeck, A, Laureys, G, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Centre de malformations vasculaires congénitales, UCL - (SLuc) Service d'hématologie et d'oncologie pédiatrique, Bauters, T, Heenen, D, Norga, K, Van Damme, A, Uyttebroeck, A, and Laureys, G
- Abstract
Treatment of children with cancer requires access to and reimbursement of effective drugs. Children with haemato-oncological diseases are often treated according to established treatment recommendations or in the framework of late-phase clinical trials. These often involve the use of drugs authorised for adults but which, however, have been used for many years in paediatrics with no perspective of authorisation in children. In Belgium, medicines are predominantly reimbursed based on their authorised indication. As a consequence, many drugs used in paediatric haemato-oncology are used off-label, despite their status of 'standard of care'. As reimbursement is often not available, alternative ways for funding need to be explored, which causes a significant administrative burden for healthcare providers and emotional distress for the parents. Solutions to organise a systematic reimbursement of standard of care off-label used drugs are described.Conclusion: A number of structural solutions are proposed, and we hope that they might guide health authorities to provide a solution to the problem caused by the lack of reimbursement of some standard of care medicines for children with cancer. What is Known: • Off-label drug use is frequently observed in paediatric haemato-oncology and compromises-in some countries-reimbursement. What is New: • An estimation of the impact of non-reimbursed drugs in Belgium is provided. • Some solutions are presented to overcome this problem in Belgium.
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- 2021
40. An integrative genomics screen uncovers ncRNA T-UCR functions in neuroblastoma tumours
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Mestdagh, P, Fredlund, E, Pattyn, F, Rihani, A, Van Maerken, T, Vermeulen, J, Kumps, C, Menten, B, De Preter, K, Schramm, A, Schulte, J, Noguera, R, Schleiermacher, G, Janoueix-Lerosey, I, Laureys, G, Powel, R, Nittner, D, Marine, J-C, Ringnér, M, Speleman, F, and Vandesompele, J
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- 2010
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41. MYCN/c-MYC-induced microRNAs repress coding gene networks associated with poor outcome in MYCN/c-MYC-activated tumors
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Mestdagh, P, Fredlund, E, Pattyn, F, Schulte, J H, Muth, D, Vermeulen, J, Kumps, C, Schlierf, S, De Preter, K, Van Roy, N, Noguera, R, Laureys, G, Schramm, A, Eggert, A, Westermann, F, Speleman, F, and Vandesompele, J
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- 2010
- Full Text
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42. RISK FACTORS WITHIN THE EUROPEAN HIGH RISK NEUROBLASTOMA HR-NBL1/SIOPEN TRIAL: PH-O120
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Ladenstein, R., Poetschger, U., Luksch, R., Brock, P., Castel, V., Yaniv, I., Papadakis, V., Laureys, G., Malis, J., Balwierz, W., Ruud, E., Kogner, P., Schroeder, H., De Lacerda, Forjaz A., Beck-Popovic, M., Bician, P., Garami, M., Trahair, T., Ambros, P., Holmes, K., Gaze, M., Pearson, A. D. J., and Valteau-Couanet, D.
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- 2014
43. Real-world experience with ocrelizumab in the msbase registry
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Butzkueven, H., Spelman, T., Ozakbas, S., Kalincik, T., Boz, C., Buzzard, K., Skibina, O., Alroughani, R., Karabudak, R., Walt, A., Lechner-Scott, J., Hodgkinson, S., Laureys, G., Hijfte, L., Terzi, M., Butler, E., Macdonell, R., Patti, F., Pesch, V., Slee, M., Barnett, M., Grammond, P., Prevost, J., Grand-Maison, F., Taylor, B., Allan Kermode, Mccombe, P., Duquette, P., Prat, A., Girard, M., Eichau Madueno, S., Izquierdo, G., Soysal, A., Sanchez-Menoyo, J. L., Sotoca, J., Muros-Le Rouzic, E., and Dirks, P.
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- 2020
44. The pitfalls and promise of liquid biopsies for diagnosing and treating solid tumors in children: a review
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Van Paemel, R., Vlug, R., De Preter, K., Van Roy, N., Speleman, F., Willems, L., Lammens, T., Laureys, G., Schleiermacher, G., Tytgat, G.A.M., Astrahantseff, K., Deubzer, H., and De Wilde, B.
- Subjects
Cancer Research - Abstract
Cell-free DNA profiling using patient blood is emerging as a non-invasive complementary technique for cancer genomic characterization. Since these liquid biopsies will soon be integrated into clinical trial protocols for pediatric cancer treatment, clinicians should be informed about potential applications and advantages but also weaknesses and potential pitfalls. Small retrospective studies comparing genetic alterations detected in liquid biopsies with tumor biopsies for pediatric solid tumor types are encouraging. Molecular detection of tumor markers in cell-free DNA could be used for earlier therapy response monitoring and residual disease detection as well as enabling detection of pathognomonic and therapeutically relevant genomic alterations. CONCLUSION: Existing analyses of liquid biopsies from children with solid tumors increasingly suggest a potential relevance for molecular diagnostics, prognostic assessment, and therapeutic decision-making. Gaps remain in the types of tumors studied and value of detection methods applied. Here we review the current stand of liquid biopsy studies for pediatric solid tumors with a dedicated focus on cell-free DNA analysis. There is legitimate hope that integrating fully validated liquid biopsy-based innovations into the standard of care will advance patient monitoring and personalized treatment of children battling solid cancers.
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- 2020
45. Real-world experience with Ocrelizumab in the MSBase Registry.
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Spelman T., Ozakbas S., Patti F., Butzkueven H., Muros-Le Rouzic E., Wormser D., Craveiro L., Van Beek J., Macdonell R., Laureys G., Prevost J., Slee M., Butler E., Soysal A., Skibina O., Hodgkinson S., Kuhle J., Barnett M., Lechner-Scott J., Van Pesch V., Kalincik T., Grammond P., Grand'Maison F., Boz C., Terzi M., Alroughani R., Eichau S., Spelman T., Ozakbas S., Patti F., Butzkueven H., Muros-Le Rouzic E., Wormser D., Craveiro L., Van Beek J., Macdonell R., Laureys G., Prevost J., Slee M., Butler E., Soysal A., Skibina O., Hodgkinson S., Kuhle J., Barnett M., Lechner-Scott J., Van Pesch V., Kalincik T., Grammond P., Grand'Maison F., Boz C., Terzi M., Alroughani R., and Eichau S.
- Abstract
Introduction: Ocrelizumab (OCR) is a humanised anti-CD20+ monoclonal antibody approved for the treatment of primary progressive multiple sclerosis (PPMS), and relapsing forms of MS, including both relapsing-remitting (RRMS) and secondary progressive (SPMS). Objective(s): In a real-world setting, to describe 1) baseline characteristics of patients with MS treated with OCR, 2) treatment pathway across lines of therapy up to initiation of OCR, and 3) initial clinical experience in patients with >=6 months follow-up data from OCR initiation Methods: Secondary data analysis using MSBase Registry data including patients with a confirmed diagnosis of MS and newly treated with OCR after regulatory approval. Descriptive statistics were used to analyze baseline patients' characteristics recorded within 3 months prior to or at time of OCR initiation, including demographics, disease course and duration, prior disease modifying therapies (DMT), and EDSS. Occurrence of relapse was analyzed in patients with >=6 months follow-up data since OCR initiation. Result(s): As of 6th March 2019, MSBase included 1216 patients newly treated with OCR (15 countries, mainly from across Europe and Australia), 882 patients with RRMS, 160 with SPMS, and 174 with PPMS. Median age at OCR initiation varied from 42.8 years, 49.2 years, to 52.4 years in patients with RRMS, SPMS, and PPMS, respectively. Most RRMS and SPMS patients were female (69.6% and 64.4%) by contrast to PPMS patients (43.1% females). Median disease duration from symptom onset up to OCR initiation was longer in SPMS (19.7 years) than in RRMS (9.7 years) and PPMS (8.7 years). Median EDSS at OCR start was 3.0, 6.5, and 6.0 in RRMS, SPMS, and PPMS, respectively. OCR was initiated as first line therapy in 11.2%, 3.1%, and 58.1% of RRMS, SPMS, and PPMS patients respectively. 583 RRMS patients initiated OCR switching from another DMT, primarily natalizumab (37.9%) and fingolimod (34.1%). 234 patients with RRMS had >=6 months follow-up dur
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- 2020
46. Delay from treatment start to full effect of immunotherapies for multiple sclerosis
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Roos, I, Leray, E, Frascoli, F, Casey, R, Brown, WJL, Horakova, D, Havrdova, EK, 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, Sá, MJ, 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, CB, Butzkueven, H, Vukusic, S, Kalincik, T, Duquette, P, Grand'Maison, F, Iuliano, G, Ramo-Tello, C, Solaro, C, Cabrera-Gomez, JA, Rio, ME, Bolaños, RF, Shaygannejad, V, Oreja-Guevara, C, Sanchez-Menoyo, JL, Petersen, T, Altintas, A, Barnett, M, Flechter, S, Fragoso, Y, Amato, MP, Moore, F, Ampapa, R, Verheul, F, Hodgkinson, S, Cristiano, E, Yamout, B, Laureys, G, Dominguez, JA, Zwanikken, C, Deri, N, Dobos, E, Vrech, C, Butler, E, Rozsa, C, Petkovska-Boskova, T, Karabudak, R, Rajda, C, Alkhaboori, J, Saladino, ML, Shaw, Cameron, Shuey, N, Vucic, S, Sempere, AP, Campbell, J, Piroska, I, Taylor, B, van der Walt, A, Kappos, L, Roullet, E, Gray, O, Simo, M, Sirbu, CA, Brochet, B, Cotton, F, de Sèze, J, Dion, A, Douek, P, Roos, I, Leray, E, Frascoli, F, Casey, R, Brown, WJL, Horakova, D, Havrdova, EK, 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, Sá, MJ, 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, CB, Butzkueven, H, Vukusic, S, Kalincik, T, Duquette, P, Grand'Maison, F, Iuliano, G, Ramo-Tello, C, Solaro, C, Cabrera-Gomez, JA, Rio, ME, Bolaños, RF, Shaygannejad, V, Oreja-Guevara, C, Sanchez-Menoyo, JL, Petersen, T, Altintas, A, Barnett, M, Flechter, S, Fragoso, Y, Amato, MP, Moore, F, Ampapa, R, Verheul, F, Hodgkinson, S, Cristiano, E, Yamout, B, Laureys, G, Dominguez, JA, Zwanikken, C, Deri, N, Dobos, E, Vrech, C, Butler, E, Rozsa, C, Petkovska-Boskova, T, Karabudak, R, Rajda, C, Alkhaboori, J, Saladino, ML, Shaw, Cameron, Shuey, N, Vucic, S, Sempere, AP, Campbell, J, Piroska, I, Taylor, B, van der Walt, A, Kappos, L, Roullet, E, Gray, O, Simo, M, Sirbu, CA, Brochet, B, Cotton, F, de Sèze, J, Dion, A, and Douek, P
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- 2020
47. Long-term results of three randomized trials (58831, 58832, 58881) in childhood acute lymphoblastic leukemia: a CLCG-EORTC report
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Vilmer, E, Suciu, S, Ferster, A, Bertrand, Y, Cavé, H, Thyss, A, Benoit, Y, Dastugue, N, Fournier, M, Souillet, G, Manel, A-M, Robert, A, Nelken, B, Millot, F, Lutz, P, Rialland, X, Mechinaud, F, Boutard, P, Behar, C, Chantraine, J-M, Plouvier, E, Laureys, G, Brock, P, Uyttebroeck, A, Margueritte, G, Plantaz, D, Norton, L, Francotte, N, Gyselinck, J, Waterkeyn, C, Solbu, G, Philippe, N, and Otten, J
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- 2000
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48. Dexamethasone (DEX) versus prednisone (PRED) in T-cell non Hodgkin lymphoma (T-NHL): results of the randomized phase III trial 58951 of the EORTC Children Leukemia Group: 68
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Uyttebroeck, A, Suciu, S, Plat, G, Laureys, G, Costa, V, Rohrlich, P, Boutard, P, Ferster, A, Nelken, B, Munzer, M, Hoyoux, C, Lutz, P, Plantaz, D, Millot, F, Sirvent, N, de Schaetzen, G, Benoit, Y, and Bertrand, Y
- Published
- 2012
49. Highly effective treatment with tacrolimus ointment in an adolescent with oral graft-versus-host disease
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Bauters, T., Bordon, V., Van de Velde, V., Van Lancker, S., Robays, H., Benoit, Y., and Laureys, G.
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- 2010
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50. Early high-dose treatment: SCT results from the European High Risk Neuroblastoma Study: O173
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Ladenstein, R., Poetschger, U., Luksch, R., Brock, P., Castel, V., Yaniv, I., Papadakis, V., Laureys, G., Malis, J., Balwierz, W., Ruud, E., Kogner, P., Schroeder, H., de Lacerda, Forjaz A.M., Beck-Popovic, M., Bician, P., Garami, M., Trahair, T., and Valteau-Couanet, D.
- Published
- 2011
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