The following article is part of conference coverage from the 2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC), held October 25-28 2021, in Orlando, Florida. Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from the 2021 CMSC Annual Meeting.


Patients with relapsing multiple sclerosis (MS) who received ponesimod had improved symptoms of fatigue compared with those who received teriflunomide, which occurred regardless of evidence of disease activity (EDA)/no evidence of disease activity (NEDA) status, according to study results presented at the 2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC), held October 25-28, 2021 in Orlando, Florida.

MS-related fatigue is one of the most common and debilitating symptoms associated with the disease. However, it’s not included in the NEDA definition, which is being increasingly used as a measure of clinical efficacy for disease-modifying therapies in relapsing MS. A previous 108-week, phase 3 OPTIMUM study, which compared ponesimod 20 mg vs teriflunomide 14 mg, found ponesimod helped patients with MS achieve NEDA compared with teriflunomide, and had a significant effect on fatigue.

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The objective of the current study was to assess whether the observed beneficial effect of ponesimod on MS-related fatigue, as seen in the 108-week, phase 3 OPTIMUM study, is truly independent from its effects on disease activity.

The 108-week, phase 3 OPTIMUM study compared patients with relapsing MS who received ponesimod 20 mg vs those who received teriflunomide 14 mg. Researchers used mixed model repeated measures to evaluate whether observed treatment differences at week 108 for MS-related fatigue symptoms with ponesimod were dependent on NEDA or EDA status. Fatigue was measured with use of the Fatigue Symptoms and Impacts Questionnaire–Relapsing Multiple Sclerosis.

A higher percentage of patients in the ponesimod group achieved NEDA-3 at week 108 compared with those in the teriflunomide group (ponesimod, 28%; teriflunomide, 18%). In addition, patients treated with ponesimod had a greater benefit in fatigue score compared with those treated with teriflunomide (least squares [LS] mean difference: –3.57, P =.0019).

Among patients with NEDA at week 108 (n=215), the LS mean difference between the 2 treatments (ponesimod – teriflunomide) regarding change from baseline fatigue was –3.17 (–7.70, 1.35) in favor of ponesimod. In comparison, at week 108 for patients with EDA (n=689), the LS mean difference between the 2 treatments regarding change from baseline fatigue was –3.36 (–5.98, –0.75) in favor of ponesimod.

The beneficial treatment differences with ponesimod were not different between NEDA and EDA patients at week 108. The LS mean difference (ponesimod – teriflunomide) in the NEDA group minus the LS mean difference (ponesimod – teriflunomide) in the EDA group was 0.19 (–5.04, 5.41) (P =.944).

“Regardless of the EDA/NEDA status at week 108, ponesimod benefit over teriflunomide on MS-related fatigue remained the same, suggesting that addressing classical clinical efficacy (NEDA/EDA definition) might not be sufficient in addressing fatigue in patients with relapsing MS,” the researchers concluded.

Disclosure: The study authors declared an affiliation with a pharmaceutical company. Please see the original reference for a full list of authors’ disclosures.


Keenan A, Turkoz I, Murray R, et al. Multiple sclerosis fatigue: treatment effect of ponesimod in relapsing multiple sclerosis patients with and without disease activity. Presented at: CMSC 2021 Annual Meeting; October 25-28, 2021; Orlando, Florida. Abstract DMT10.