No higher early MS relapse frequency after stopping ponesimod

In a post-hoc analysis of the OPTIMUM study, short-term observational data in patients who stopped ponesimod for 6-168 days did not suggest a higher early relapse frequency than during treatment, or compared with teriflunomide. Furthermore, there was no clear pattern of disease reactivation, nor an indication that post-treatment relapses were usually severe or leading to persistent disability.

Ponesimod is an orally active, selective S1P1-receptor modulator that induces rapid, dose-dependent, and reversible reductions in peripheral blood lymphocyte count. In the phase 3 OPTIMUM study (NCT02425644), ponesimod 20 mg demonstrated superior efficacy versus teriflunomide 14 mg in reducing annualised relapse rate (ARR) in patients with relapsing MS [1]. Cases of exacerbation of MS activity have been reported after discontinuation of S1P1-receptor modulators.

Prof. Ludwig Kappos (University of Basel, Switzerland) reported on the post-treatment relapse activity in the OPTIMUM study [2]. He explained that all patients who completed treatment in the OPTIMUM study after 108 weeks, regardless of treatment group, interrupted treatment for at least 2 weeks and, for teriflunomide, underwent an accelerated elimination procedure. All patients who stopped treatment, either prematurely or not, entered safety follow-up (at least 30 days after the last dose), and a post-treatment observation period (from the last dose up to 108 weeks after randomisation).

Of 1,133 randomised patients, 1,124 had post-treatment observation. In the ponesimod and teriflunomide group, 88 and 92 patients stopped treatment prematurely, respectively. Eight patients in the ponesimod group and 14 in the teriflunomide group experienced a total of 23 post-treatment relapses within 182 days of the last received dose of either study drug. Post-treatment ARR did not exceed on-treatment ARR for both drugs. Including non-confirmed relapses, ARR in the ponesimod group was 0.246 on-treatment, and 0.186 off-treatment; ARR in the teriflunomide group was 0.348 and 0.294, respectively. These findings are consistent with the main OPTIMUM results up to the end of the study. There were 8 confirmed on-treatment relapses in 5 ponesimod-treated patients, and 9 relapses (3 confirmed) in 8 patients between 6 and 168 days post-treatment, without any pattern of latency or severity.

1. Kappos L, et al. JAMA Neurol. 2021 May 1;78(5):558-67.
2. Kappos L, et al. Analysis of post-treatment relapse activity in the phase 3 OPTIMUM study of ponesimod compared with teriflunomide. OPR-208, EAN 2021 Virtual Congress, 19–22 June.

 

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Posted on 18 August 202118 August 2021