BACKGROUND: Brain volume loss (BVL) is accelerated in patients with multiple sclerosis (MS), occurring early in the disease course, and is associated with worsening of long-term disability. To our knowledge, no network meta-analyses (NMAs) have been published assessing the relative efficacy of treatments for relapsing MS (RMS) regarding BVL.
OBJECTIVE: To estimate the relative efficacy of teriflunomide versus (vs) other approved disease-modifying therapies (DMTs) in terms of BVL percentage change from baseline (%CFB) at 12 and 24 months in patients with RMS using an NMA.
METHODS: MEDLINE, Embase, and CENTRAL databases were searched (up to August 2020) using a predefined search strategy and Population, Intervention, Comparators, Outcomes, and Study Type selection criteria for randomized controlled trials of DMTs in patients with RMS. Abstracts and publications were independently reviewed; data on study design, patient characteristics, and outcomes were extracted in a predefined extraction file. 18 trials were assessed and retained for the NMA. Bayesian NMAs using random-effects models were conducted. Sensitivity analyses were also performed.
RESULTS: The primary NMAs of BVL %CFB to 12 and 24 months included 14 and 12 trials, respectively. Data were available for placebo and 11 DMTs: dimethyl fumarate, fingolimod, glatiramer acetate, intramuscular interferon β 1a, natalizumab, ocrelizumab (sensitivity analysis only), ofatumumab, ozanimod, ponesimod, subcutaneous interferon β-1a, and teriflunomide. Primary results suggested numerical differences in favor of teriflunomide 14 mg vs most other DMTs at each timepoint. At 12 months, there was statistically significant evidence in favor of teriflunomide 14 mg vs natalizumab (mean difference in BVL %CFB [95% credible interval]: 0.47 [0.09–0.85]), ofatumumab (0.19 [0.02–0.36]), and placebo (0.31 [0.02–0.60]). Teriflunomide 14 mg had the highest probability of ranking best (0.598). At 24 months, there was statistically significant evidence in favor of teriflunomide 14 mg vs placebo (0.46 [0.04–0.88]). Estimates from sensitivity analyses were consistent with those of the primary NMA. Further, results were in favor of teriflunomide 14 mg vs ocrelizumab at both 12 and 24 months (not statistically significant).
CONCLUSIONS: This study provides an initial understanding of comparative BVL for patients with RMS, encompassing an outcome not previously assessed in NMAs. Most DMTs were similar in their reductions in BVL when compared with teriflunomide, with some evidence favoring teriflunomide at 12 and 24 months.
