Risk for Multiple Sclerosis Relapse After Ponesimod Therapy Discontinuation

Researchers sought to determine whether patients who discontinued treatment with ponesimod had an increased risk for MS disease activity exacerbation.

Patients with multiple sclerosis (MS) who discontinued ponesimod treatment were not found to have higher rates of early posttreatment relapse activity compared with their activity on treatment, according to study results presented at the 2022 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) held from June 1-4, in National Harbor, Maryland.

Previous studies have found that patients who prematurely discontinued treatment with sphingosine-1-phosphate receptor modulators were at risk for MS disease activity exacerbation. To evaluate whether these trends also apply to ponesimod, data from the OPTIMUM trial were analyzed for this study.

The OPTIMUM study was a phase 3 clinical trial which randomized patients (N=1133) with MS in a 1:1 ratio to receive 20 mg ponesimod or 14 mg teriflunomide once daily for 108 weeks. Early posttreatment relapse activity was evaluated from treatment discontinuation to up to 108 weeks after randomization.

Among the 1124 patients with sufficient follow-up data, 559 received ponesimod and 565 teriflunomide.

The median posttreatment follow-up was 31.6 (range, 1-182) days for the ponesimod and 30.8 (range, 1-182) days for the teriflunomide recipients. During the follow-up, 23 posttreatment relapses occurred among 8 patients who received ponesimod and 14 who received teriflunomide.

Among the ponesimod cohort, 3 relapse events were confirmed, 4 were unconfirmed, and the status of 2 were unknown. No patterns of latency or severity were observed.

The relapse rate posttreatment was not higher than the rate observed during ponesimod treatment (annualized relapse rate, 0.186% vs 0.246%), respectively.

This study may have been limited by its short median posttreatment follow-up. It remains unclear whether these trends will continue long-term.

Posttreatment follow-up data from the OPTIMUM clinical trial indicated that fewer patients who discontinued ponesimod treatment experienced posttreatment MS relapse activity than patients who discontinued teriflunomide.

“These prospectively obtained posttreatment observation data in patients who stopped ponesimod treatment in the OPTIMUM study do not support increased early posttreatment relapse activity compared with activity on treatment,” the researchers concluded.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Kappos L, Fox RJ, Burcklen M, et al. Analysis of Posttreatment Relapse Activity in the Phase 3 Optimum Study of Ponesimod Compared With Teriflunomide. Presented at: CMSC 2022 Annual Meeting; June 1-4, 2022; National Harbor, Maryland. Abstract DMT38.