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Title: Comparison Between Dimethyl Fumarate, Fingolimod, and Ocrelizumab After Natalizumab Cessation.
Austin 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
Affiliation: Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Clinical Outcomes Research Unit (CORe), Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.;Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Charles University in Prague and General University Hospital, Prague, Czech Republic.
School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.;Department of Neurology, Box Hill Hospital, Melbourne, Victoria, Australia.;Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia.
Amiri Hospital, Sharq, Kuwait.
Hospital Universitario Virgen Macarena, Sevilla, Spain.
University Hospital and University of Basel, Basel, Switzerland.
Multiple Sclerosis Center, University of Catania, Catania, Italy.
Neuro Rive-Sud, Longueuil, Québec, Canada.
Liverpool Hospital, Sydney, New South Wales, Australia.
CISSS Chaudière-Appalache, Levis, Québec, Canada.
University Newcastle, Newcastle, New South Wales, Australia.
Monash Medical Centre, Melbourne, Victoria, Australia.
CHUM MS Center and Université de Montréal, Montréal, Québec, Canada.
Austin Health
Buffalo General Medical Center, Buffalo, New York.
Dokuz Eylul University, Konak/Izmir, Turkey.
Flinders University, Adelaide, South Australia, Australia.
Centro Hospitalar Universitario de São João, Porto, Portugal.
Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Brain and Mind Centre, Sydney, New South Wales, Australia.
Rehabilitation and MS-Centre Overpelt and Hasselt University, Hasselt, Belgium.
Zuyderland Medical Center, Sittard-Geleen, the Netherlands.
CSSS Saint-Jérôme, Saint-Jerome, Québec, Canada.
19 Mayis University, Samsun, Turkey.
KTU Medical Faculty Farabi Hospital, Trabzon, Turkey.
Universitary Hospital Ghent, Ghent, Belgium.
University of Western Australia, Nedlands, Western Australia, Australia.
Westmead Hospital, Sydney, New South Wales, Australia.
American University of Beirut Medical Center, Beirut, Lebanon.
Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Issue Date: 1-Jul-2023
Date: 2023
Publication information: JAMA Neurology 2023-07-01; 80(7)
Abstract: 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. To compare the effectiveness and persistence of dimethyl fumarate, fingolimod, and ocrelizumab among patients with relapsing-remitting multiple sclerosis (RRMS) who discontinued natalizumab. 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. Dimethyl fumarate, fingolimod, and ocrelizumab. 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. 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. 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.
DOI: 10.1001/jamaneurol.2023.1542
Journal: JAMA Neurology
PubMed URL: 37273217
ISSN: 2168-6157
Type: Journal Article
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