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Abstract Details

Network Meta-Analysis for Cumulative Disability Accumulation in Relapsing Multiple Scelorsis
Multiple Sclerosis
P16 - Poster Session 16 (5:30 PM-6:30 PM)
9-016

To assess the effect of ponesimod on confirmed disability accumulation (CDA) relative to other disease-modifying therapies (DMTs) for the treatment of relapsing multiple sclerosis (RMS).
Ponesimod is a selective sphingosine-1-phosphate (S1P) receptor 1 immunomodulator currently in development for the treatment of RMS. The recently completed OPTIMUM study provided evidence that ponesimod was numerically superior to teriflunomide in delaying disability progression (hazard ratio [HR]: 0.83; 95% confidence interval: 0.58–1.18). To estimate the relative effect of ponesimod compared with other treatments on CDA, a network meta-analysis (NMA) was performed.
A systematic literature review was conducted by updating recent systematic reviews of treatments for RMS. Medline, Embase, and Cochrane were searched to identify published randomized controlled trials in RMS up to March 2019. A Bayesian NMA was performed for 3-month CDA as recommended by the National Institute of Health and Care Excellence, and treatments were ranked using the surface under the cumulative ranking curve (SUCRA).
Fourteen trials were included in the NMA, assessing 12 treatment regimens using 10 DMTs. Interferon β-1b was excluded due to disconnection from the main network. NMA results suggest that ponesimod is statistically more effective in delaying disability progression compared to placebo (HR: 0.57; 95% credible interval: 0.34–0.96) and has numerically superior efficacy to 8 of the 12 treatments, including  the S1P receptor modulator fingolimod, as well as teriflunomide, interferon β-1a, and dimethyl fumarate (HR range, 0.62–0.98).  Using SUCRA values, ponesimod was ranked fourth, after alemtuzumab, ocrelizumab, and natalizumab; compared to teriflunomide 14 mg which ranked eighth among the 12 treatments.
Ponesimod delays disability accumulation, with an absolute effect size statistically superior to placebo and numerically superior to most currently available DMTs for RMS. Results of the NMA are limited due to the small number of trials reporting HR for CDA.
Authors/Disclosures
Alexander Keenan
PRESENTER 		Alexander Keenan has received personal compensation for serving as an employee of Janssen Pharmaceuticals. Alexander Keenan has received stock or an ownership interest from Johnson and Johnson.
No disclosure on file
No disclosure on file
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