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Rituximab versus Fingolimod after Natalizumab in Multiple Sclerosis Patients

Artikel i vetenskaplig tidskrift
Författare P. Alping
T. Frisell
Lenka Novakova
P. Islam-Jakobsson
J. Salzer
A. Bjorck
Markus Axelsson
Clas Malmeström
K. Fink
Jan Lycke
A. Svenningsson
F. Piehl
Publicerad i Annals of Neurology
Volym 79
Nummer/häfte 6
Sidor 950-958
ISSN 0364-5134
Publiceringsår 2016
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering
Sidor 950-958
Språk en
Länkar dx.doi.org/10.1002/ana.24651
Ämnesord PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY, RISK STRATIFICATION, ORAL, FINGOLIMOD, DOUBLE-BLIND, TRIAL, THERAPY
Ämneskategorier Neurovetenskap

Sammanfattning

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%; Umea, 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.

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