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Rituximab versus fingolimod after natalizumab in multiple sclerosis patients
Author(s) -
Alping Peter,
Frisell Thomas,
Novakova Lenka,
IslamJakobsson Protik,
Salzer Jonatan,
Björck Anna,
Axelsson Markus,
Malmeström Clas,
Fink Katharina,
Lycke Jan,
Svenningsson Anders,
Piehl Fredrik
Publication year - 2016
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24651
Subject(s) - fingolimod , natalizumab , medicine , rituximab , multiple sclerosis , progressive multifocal leukoencephalopathy , hazard ratio , odds ratio , adverse effect , confidence interval , immunology , lymphoma
Objective Many JC virus antibody‐positive relapsing–remitting multiple sclerosis (RRMS) patients who are stable on natalizumab switch to other therapies to avoid progressive multifocal leukoencephalopathy. Methods We compared outcomes for all RRMS patients switching from natalizumab due to JC virus antibody positivity at 3 Swedish multiple sclerosis centers with different preferential use of rituximab and fingolimod (Stockholm, n = 156, fingolimod 51%; Gothenburg, n = 64, fingolimod 88%; Umeå, n = 36, fingolimod 19%), yielding a total cohort of N = 256 (fingolimod 55%). Results Within 1.5 years of cessation of natalizumab, 1.8% (rituximab) and 17.6% (fingolimod) of patients experienced a clinical relapse (hazard ratio for rituximab = 0.10, 95% confidence interval [CI] = 0.02–0.43). The hazard ratio (favoring rituximab) for adverse events (5.3% vs 21.1%) and treatment discontinuation (1.8% vs 28.2%) were 0.25 (95% CI = 0.10–0.59) and 0.07 (95% CI = 0.02–0.30), respectively. Furthermore, contrast‐enhancing lesions were found in 1.4% (rituximab) versus 24.2% (fingolimod) of magnetic resonance imaging examinations (odds ratio = 0.05, 95% CI = 0.00–0.22). Differences remained when adjusting for possible confounders (age, sex, disability status, time on natalizumab, washout time, follow‐up time, and study center). Interpretation Our findings suggest an improved effectiveness and tolerability of rituximab compared with fingolimod in stable RRMS patients who switch from natalizumab due to JC virus antibody positivity. Although residual confounding factors cannot be ruled out, the shared reason for switching from natalizumab and the preferential use of either rituximab or fingolimod in 2 of the centers mitigates these concerns. Ann Neurol 2016;79:950–958