Alping et al. Rituximab versus fingolimod after natalizumab in multiple sclerosis patients. Ann Neurol. 2016 Mar 31. doi: 10.1002/ana.24651.
OBJECTIVE: Many JC-virus antibody positive relapsing-remitting multiple sclerosis (RRMS) patients stable on natalizumab switch to other therapies to avoid progressive multifocal leukoencephalopathy (PML).
METHODS: We compared outcomes for all RRMS patients switching from natalizumab due to JC-virus antibody positivity at three Swedish MS centres with different preferential use of rituximab and fingolimod, respectively; Stockholm n=156 (fingolimod 51%); Gothenburg n=64 (fingolimod 88%); UmeƄ 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% CI: 0.02-0.43)). The hazard ratio (favouring 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) vs 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 centre).
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 two of the centres mitigates these concerns. This article is protected by copyright. All rights reserved.