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Title: | Comparison Between Dimethyl Fumarate, Fingolimod, and Ocrelizumab After Natalizumab Cessation | Authors: | Zhu, Chao Kalincik, Tomas Horakova, Dana Zhou, Zhen Buzzard, Katherine Skibina, Olga Alroughani, Raed Izquierdo, Guillermo Eichau, Sara Kuhle, Jens Patti, Francesco Grand'Maison, Francois Hodgkinson, Suzanne Grammond, Pierre Lechner-Scott, Jeannette Butler, Ernest Prat, Alexandre Girard, Marc Duquette, Pierre Macdonell, Richard A. L. Weinstock-Guttman, Bianca Ozakbas, Serkan Slee, Mark Sa, Maria Jose Van Pesch, Vincent Barnett, Michael VAN WIJMEERSCH, Bart Gerlach, Oliver Prevost, Julie Terzi, Murat Boz, Cavit Laureys, Guy Van Hijfte, Liesbeth Kermode, Allan G. Garber, Justin Yamout, Bassem Khoury, Samia J. Merlo, Daniel Monif, Mastura Jokubaitis, Vilija van der Walt, Anneke Butzkueven, Helmut MSBase Study Grp |
Issue Date: | 2023 | Publisher: | AMER MEDICAL ASSOC | Source: | JAMA Neurology, 80 (7), p. 739-748 | 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 each medication was as follows: ocrelizumab, 0.06 (95% CI, 0.04-0.08); fingolimod, 0.26 (95% CI, 0.12-0.48); and dimethyl fumarate, 0.27 (95% CI, 0.12-0.56). The ARR ratio of fingolimod to ocrelizumab was 4.33 (95% CI, 3.12-6.01) and of dimethyl fumarate to ocrelizumab was 4.50 (95% CI, 2.89-7.03). Compared with ocrelizumab, the hazard ratio (HR) of time to first relapse was 4.02 (95% CI, 2.83-5.70) for fingolimod and 3.70 (95% CI, 2.35-5.84) for dimethyl fumarate. The HR of treatment discontinuation was 2.57 (95% CI, 1.74-3.80) for fingolimod and 4.26 (95% CI, 2.65-6.84) for dimethyl fumarate. Fingolimod use was associated with a 49% higher risk for disability accumulation compared with ocrelizumab. There was no significant difference in disability improvement rates between fingolimod and ocrelizumab.CONCLUSION AND RELEVANCE Study results show that among patients with RRMS who switched from natalizumab to dimethyl fumarate, fingolimod, or ocrelizumab, ocrelizumab use was associated with the lowest ARR and discontinuation rates, and the longest time to first relapse. | Notes: | Zhu, C (corresponding author), Monash Univ, Cent Clin Sch, Dept Neurosci, 99 Commercial Rd,Level 6, Melbourne, Vic 3004, Australia. chao.zhu@monash.edu |
Document URI: | http://hdl.handle.net/1942/40565 | ISSN: | 2168-6149 | e-ISSN: | 2168-6157 | DOI: | 10.1001/jamaneurol.2023.1542 | ISI #: | 001003639300001 | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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