Switching from natalizumab to fingolimod kept 85% of multiple sclerosis patients relapse-free for at least 6 months in an observational cohort study.
Although relapse rates remained low after patients started fingolimod, patients who had a gap of 2-4 months between cessation of prior treatment and commencement of fingolimod had significantly higher relapse rates than did those with no treatment gap.
"The main risk factor for time to relapse on fingolimod was recent prior relapse," said Dr. Vilija Jokubaitis of the University of Melbourne and her associates. "Our data support choosing a short switch period (2 months or less) between prior treatment and fingolimod to decrease the hazard of relapse," they added.
Because of concerns about progressive multifocal leukoencephalopathy (PML), patients with multiple sclerosis (MS) often are switched to fingolimod (Gilenya) if they have taken natalizumab (Tysabri) for more than 24 months and test positive for anti-JC virus antibodies. To evaluate the effects of switching on MS relapse, the researchers studied 536 patients from the MSBase Registry who took fingolimod as initial therapy (n = 97), switched to fingolimod after failing natalizumab (n = 89), or switched to fingolimod from interferon-beta/glatiramer acetate (n = 350). The median washout period for patients switching from natalizumab to fingolimod was 79 days (interquartile range, 57-96 days), and the median follow-up for all patients was 10.3 months, the investigators reported (Neurology 2014 March 7 [doi: 10.1212/WNL.0000000000000283]).
Relapse rates were "relatively stable" among the patients who switched from natalizumab to fingolimod during the first 9 months on fingolimod (quarterly relapse rate range, 0.079-0.13), compared with the 15-month period before starting fingolimod (quarterly relapse rate range, 0.05-0.11). Patients who switched from natalizumab to fingolimod had a small increase in annualized relapse rate (0.38 vs. 0.26 for natalizumab; P = .002), which the investigators attributed to possible differences in efficacy between the two medications. In survival analyses, predictors of time to first relapse on fingolimod included number of relapses in the past 6 months (hazard ratio, 1.60 per relapse; P = .002) and a treatment gap of 2-4 months vs. no gap (HR, 2.10; P = .041).
"In this study, the largest of its kind to date, we found no evidence to support the occurrence of clinical rebound in patients switching from natalizumab to fingolimod," wrote Dr. Jokubaitis and her associates. Relapse activity was well-controlled in this patient group, and it was similar to relapse activity in patients switching to fingolimod from interferon-beta/glatiramer acetate or those starting fingolimod as their first disease-modifying therapy for MS.
The study was funded by a grant from the Australian National Health and Medical Research Council and by the MSBase Foundation. Dr. Jokubaitis and 13 of her associates reported having received honoraria or other support from Novartis, which makes fingolimod. Ten associates reported receiving honoraria or other support from Biogen Idec, which makes natalizumab.