Author Of 1 Presentation
P0049 - Comparative Efficacy of Relapsing Multiple Sclerosis Therapies: A Model-Based Meta-Analysis for Annual Relapse Rate (ID 1256)
Abstract
Background
Multiple sclerosis (MS), an inflammatory autoimmune disorder, is responsible for progressive neurological disability among young adults. Ponesimod is a selective sphingosine-1-phosphate (S1P) receptor 1 immunomodulator under development for relapsing multiple sclerosis (RMS).
Objectives
To assess the effect of ponesimod on the annual relapse rate (ARR) relative to other disease-modifying therapies (DMTs) for treatment of RMS.
Methods
A literature review was performed and a database with 154 unique clinical trials with 58 MS treatments was created. This database was filtered to include randomized controlled trials (RCTs) with >30 patients receiving monotherapy to treat RMS for at least 48 weeks. Mean ARR for each treatment arm was modeled and rate ratios (RRs) between treatments were assumed constant from 48 to 156 weeks. Multiple arm-level variables were explored as modifiers of relative treatment effect: percent of patients with remitting RMS, trial start year, mean disease duration, percent of patients with history of DMT use in past 2 years (pDMT), mean relapses in prior year, mean age, and mean baseline EDSS score.
Results
The model utilized mean ARR data from 41 RCTs in RMS (18 unique treatments [including placebo], 106 treatment arms, 33,904 patients). Rate ratios were estimated for all 17 treatments vs. placebo. A dose-response relationship was included if data at multiple doses were available and results indicated a potential dose-dependent effect (8 treatments). Relative treatment effect was smaller in trials with higher pDMT. In addition to superiority of ponesimod vs. teriflunomide, results suggested that ponesimod reduced ARR significantly compared to placebo (RR: 0.47; 95% CI: 0.32–0.68), interferon β-1a (intramuscular, 0.57; 0.39–0.85), laquinimod (0.58; 0.38–0.88), and interferon β-1b (0.65; 0.44–0.97). Results suggested that ponesimod had numerically superior ARR benefits compared to interferon β-1a (subcutaneous), peginterferon β-1a, glatiramer acetate, and dimethyl fumarate (RR range: 0.68–0.94). Ponesimod had similar ARR benefits to S1P receptor modulators ozanimod, fingolimod, cladribine, and daclizumab (RR range: 1.00–1.04).
Conclusions
Ponesimod reduced ARR in patients with RMS, and was statistically superior as compared with placebo and a range of other DMTs.