Beyond First-Line: Natalizumab vs Fingolimod for Relapsing-Remitting Multiple Sclerosis

For patients with multiple sclerosis (MS) who are treated with injectable disease-modifying therapies (DMTs) for more than 2 years, the risk of relapse is 55 to 80%, and the risk of disability progression is 33 to 46%.¹ Patients who demonstrate suboptimal response to these therapies are often switched to natalizumab (Tysabri) or fingolimod (Gilenya) for treatment escalation. Though these agents are considered to have higher efficacy than the injectable DMTs, there is limited data regarding their impact in breakthrough disease.²

A study published in March 2015 in the Annals of Neurology is the first to compare the effects of switching to natalizumab or fingolimod in patients with relapsing-remitting MS (RRMS) who have continued disease activity despite treatment with injectable DMTs.²

“Given practical and financial limitations, it is unlikely that escalation to natalizumab or fingolimod will be directly compared in a randomized head-to-head trial,” the authors wrote. “A feasible alternative strategy is to utilize existing longitudinal registries of clinical outcomes data.” Using data from the MSBase observational cohort study, researchers conducted a propensity score-matched analysis of 578 patients who had switched from injectable DMTs to natalizumab (407 patients) or fingolimod (171 patients) after documented breakthrough disease activity within the previous 6 months. In the 2 years post-switch, the investigators found that while both agents reduced relapse activity and disability, natalizumab was more effective. There was a decrease in annualized relapse rates from 1.5 to 0.2 for natalizumab and from 1.3 to 0.3 for fingolimod, and rates of 6-month sustained disability regression were 2.8 times higher after switching to natalizumab vs fingolimod.

CLINICAL CHART: Multiple Sclerosis Treatments

“When a first-line injectable therapy has not had a sufficient effect, escalation of therapy to a more potent agent is preferred over switching to another agent within the same category of therapies,” study co-author Tomas Kalincik, MD, PhD, a research fellow at the University of Melbourne in Australia, told Neurology Advisor. “There are a number of candidate therapies, and choosing the right one is a complex process that involves careful consideration of the individual patient’s life circumstances, family plans, experience with previous therapies, preferred route of administration, concomitant diseases, and treatment efficacy.”