Ponesimod More Effective than Teriflunomide at Treating Relapsing Multiple Sclerosis
Ponesimod appears significantly more effective at reducing the annualized relapse rate in patients with multiple sclerosis (MS) when compared with teriflunomide, according to a randomized phase 3 clinical trial published in JAMA Neurology.
The multicenter, double-blind phase 3 trial, Oral Ponesimod Versus Teriflunomide In Relapsing Multiple Sclerosis (OPTIMUM), is the first known active-comparator trial of oral disease-modifying therapies for relapsing MS.
Researchers enrolled 1133 adult patients with relapsing MS, per the 2010 McDonald Criteria, each with confirmed relapse. Efficacy, safety, and tolerability of each therapy was compared by randomizing 567 patients to receive 20 mg of ponesimod and 566 patients to receive 14 mg of teriflunomide once daily for the 108-week trial period.
The primary efficacy endpoint was the annualized relapse rate. Researchers also analyzed changes in the Fatigue Symptom and Impact Questionnaire–Relapsing Multiple Sclerosis (FSIQ–RMS), the amount of combined unique active lesions (CUALs) recorded through magnetic resonance imaging (MRI) scans, and confirmed disability accumulation in each patient.
A statistical analysis was performed on the full randomized group using a negative binomial regression model to show the number of confirmed relapses from the beginning to end of study.
Ponesimod reduced the annualized relapse rate in patients by 30.5% (0.202 vs 0.290; P < .001) compared to teriflunomide. Researchers recorded 242 total confirmed relapses for patients in the ponesimod arm compared with 344 in the teriflunomide arm.
Ponesimod was also found to reduce the group FSIQ–RMS score and CUALs in MRI scans; patients in the ponesimod arm saw decreased levels of fatigue and a 56% reduction in the mean number of CUALs per year.
Under both therapies, the risk of 12-week confirmed disability accumulation was the same. Treatment-emergent adverse events were similar in both groups.
“Ponesimod was superior to teriflunomide, an oral pyrimidine synthesis inhibitor approved for the treatment of MS on the primary study outcome, reduction of ARR (by −30.5%),” wrote Ludwig Kappos, MD, University of Basel, Basel, Switzerland, and co-investigators.
“Superiority vs teriflunomide was also shown in the analysis of 2 key secondary outcomes: the reduction of CUAL, an established MRI measure of focal inflammatory disease activity (−56%), and improvement of MS-associated fatigue, as measured with the FSIQ-RMS weekly symptom score (mean difference, −3.57).”—Erin McGuinness
Kappos L, Fox RJ, Burcklen M, et al. Ponesimod Compared With Teriflunomide in Patients With Relapsing Multiple Sclerosis in the Active-Comparator Phase 3 OPTIMUM Study: A Randomized Clinical Trial. JAMA Neurol. Published online March 29, 2021. doi:10.1001/jamaneurol.2021.0405