BACKGROUND: Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years. METHODS: In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts. Longitudinal clinical data were obtained from 71 MSBase centres in 21 countries and from six non-MSBase centres in the UK and Germany between Nov 1, 2015, and June 30, 2016. Key inclusion criteria were a diagnosis of definite relapsing-remitting multiple sclerosis, exposure to one of the study therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Expanded Disability Status Scale (EDSS) score 6·5 or lower, and no more than 10 years since the first multiple sclerosis symptom. The primary endpoint was annualised relapse rate. The secondary endpoints were cumulative hazards of relapses, disability accumulation, and disability improvement events. We compared relapse rates with negative binomial models, and estimated cumulative hazards with conditional proportional hazards models. FINDINGS: Patients were treated between Aug 1, 1994, and June 30, 2016. The cohorts consisted of 189 patients given alemtuzumab, 2155 patients given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab. Alemtuzumab was associated with a lower annualised relapse rate than interferon beta (0·19 [95% CI 0·14-0·23] vs 0·53 [0·46-0·61], p<0·0001) and fingolimod (0·15 [0·10-0·20] vs 0·34 [0·26-0·41], p<0·0001), and was associated with a similar annualised relapse rate as natalizumab (0·20 [0·14-0·26] vs 0·19 [0·15-0·23], p=0·78). For the disability outcomes, alemtuzumab was associated with similar probabilities of disability accumulation as interferon beta (hazard ratio [HR] 0·66 [95% CI 0·36-1·22], p=0·37), fingolimod (1·27 [0·60-2·70], p=0·67), and natalizumab (0·81 [0·47-1·39], p=0·60). Alemtuzumab was associated with similar probabilities of disability improvement as interferon beta (0·98 [0·65-1·49], p=0·93) and fingolimod (0·50 [0·25-1·01], p=0·18), and a lower probability of disability improvement than natalizumab (0·35 [0·20-0·59], p=0·0006). INTERPRETATION: Alemtuzumab and natalizumab seem to have similar effects on annualised relapse rates in relapsing-remitting multiple sclerosis. Alemtuzumab seems superior to fingolimod and interferon beta in mitigating relapse activity. Natalizumab seems superior to alemtuzumab in enabling recovery from disability. Both natalizumab and alemtuzumab seem highly effective and viable immunotherapies for multiple sclerosis. Treatment decisions between alemtuzumab and natalizumab should be primarily governed by their safety profiles. FUNDING: National Health and Medical Research Council, and the University of Melbourne.

Abertawe Bro Morgannwg University Local Health Board Swansea UK

Amiri Hospital Qurtoba Kuwait City Kuwait

Azienda Ospedaliera San Giuseppe Moscati di Avellino Avellino Italy

Azienda Sanitaria Unica Regionale Marche AV3 Macerata Italy

Brain and Mind Centre Camperdown NSW Australia

C Mondino National Neurological Institute Pavia Italy

Center of Clinical Neuroscience Department of Neurology MS Center Dresden Dresden Germany; Center of Clinical Neuroscience University Hospital Carl Gustav Carus Dresden University of Technology Dresden Germany

Centres intégrés de santé et de services sociaux de Chaudière Appalache Levis QC Canada

Cliniques Universitaires Saint Luc Brussels Belgium

Department of Basic Medical Sciences Neuroscience and Sense Organs University of Bari Bari Italy

Department of Biomedical and Neuromotor Sciences University of Bologna Bologna Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna Bologna Italy

Department of Clinical Neurosciences University of Cambridge Cambridge UK

Department of Medicine University of Melbourne Melbourne VIC Australia; Department of Neurology Royal Melbourne Hospital 300 Grattan St Melbourne 3050 Australia

Department of Medicine University of Melbourne Melbourne VIC Australia; Department of Neurology Royal Melbourne Hospital 300 Grattan St Melbourne 3050 Australia; Department of Neurology Box Hill Hospital Monash University Melbourne VIC Australia

Department of Neurology and Center of Clinical Neuroscience General University Hospital and Charles University Prague Czech Republic

Department of Neurology Institute of Psychological Medicine and Clinical Neuroscience Cardiff University University Hospital of Wales Cardiff UK

Department of Neurology Southmead Hospital Westbury on Trym Bristol UK; School of Clinical Sciences University of Bristol Bristol UK

Flinders University Adelaide SA Australia

Groene Hart Ziekenhuis Gouda Netherlands

Hopital Notre Dame Montreal QC Canada; Centre hospitalier de l'Université de Montréal Montreal QC Canada; Université de Montreal Montreal QC Canada

Hospital de Galdakao Usansolo Galdakao Spain

Hospital Germans Trias i Pujol Badalona Spain

Hospital Italiano Buenos Aires Argentina

Hospital Universitario Donostia San Sebastián Spain

Hospital Universitario Virgen Macarena Sevilla Spain

Jahn Ferenc Teaching Hospital Budapest Hungary

KTÜ Medical Faculty Farabi Hospital Karadeniz Technical University Trabzon Turkey

Liverpool Hospital Sydney NSW Australia

Medical Faculty 19 Mayis University Kurupelit Samsun Turkey

Nemocnice Jihlava Jihlava Czech Republic

Neuro Rive Sud Greenfield Park QC Canada

NMR Research Unit Queen Square Multiple Sclerosis Centre University College London Institute of Neurology London UK; Department of Clinical Neurosciences University of Cambridge Cambridge UK

Nuovo Ospedale Civile Sant'Agostino Estense Modena Italy

Royal Brisbane and Women's Hospital Brisbane QLD Australia

School of Medicine and Medical Sciences University College Dublin St Vincent's University Hospital Dublin Ireland

Semmelweis University Budapest Budapest Hungary

University of Debrecen Faculty of Medicine Department of Neurology Debrecen Hungary

University of Newcastle Newcastle NSW Australia

University of Parma Parma Italy

Westmead Hospital Sydney NSW Australia

Zuyderland Ziekenhuis Sittard Netherlands

Komentář v

Lancet Neurol. 2017 Apr;16(4):252-253. doi: 10.1016/S1474-4422(17)30021-2. PubMed

Komentář v

J Neurol. 2023 Oct;270(10):5127-5129. doi: 10.1007/s00415-023-11984-9. PubMed

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