In patients with multiple sclerosis (MS), treatment with teriflunomide shows promise in preventing a first clinical demyelinating event, according to study findings published in JAMA Neurology.
In the double-blind, phase 3, randomized clinical trial, Teriflunomide in Radiologically Isolated Syndrome (TERIS; ClinicalTrials.gov Identifier: NCT03122652), researchers reported on the efficacy of teriflunomide in delaying the progression of MS in adult patients who met the 2009 radiologically isolated syndrome (RIS) criteria.
The researchers defined the primary outcome as the duration until the initial acute or progressive neurologic event related to central nervous system (CNS) demyelination. Secondary outcomes consisted of specific brain magnetic resonance imaging (MRI) metrics.
Although the researchers initially screened 124 patients who met RIS criteria, study enrollment decreased to 89 following exclusions and dropouts. In a 1:1 ratio, the researchers randomly assigned 45 of these patients to receive a placebo and 44 to receive a daily 14-mg dose of teriflunomide.
- loss to follow-up (5 [27.8%]);
- consent withdrawal (4 [22.2%]);
- voluntary withdrawal (4 [22.2%]);
- adverse events (3 [16.7%]);
- pregnancy (1 [5.6%]); and
- study termination (1 [5.6%]).
- optic nerve (4 [16.7%]);
- spinal cord (8 [33.3%]);
- brain stem/cerebellum (3 [12.5%]);
- long sensory nerves (6 [25%]); and
- motor tracts (3 [12.5%]).
Compared with participants in the placebo group, participants in the teriflunomide group experienced longer times to the first clinical event according to both the unadjusted (HR, 0.37; 95% CI, 0.16-0.84; P =.02) and adjusted (HR, 0.28; 95% CI, 0.11-0.71; P =.007) analyses. This result corresponded to a 63% unadjusted risk reduction of the first clinical event for participants in the teriflunomide group.
Secondary imaging endpoints, such as the cumulative number of new or newly enlarging T2 lesions (rate ratio [RR], 0.57; 95% CI, 0.27-1.20; P =.14), new gadolinium-enhancing lesions (RR, 0.33; 95% CI, 0.09-1.17; P =.09), and the proportion of participants with new lesions (OR, 0.72; 95% CI, 0.25-2.06; P =.54), did not show statistical significance.
The most frequent adverse events (AEs) in patients treated with teriflunomide were gastrointestinal disorders (11.4%) and dysmenorrhea (9.1%).
Study limitations included the researchers’ inability to categorize high-risk subgroups according to the risk factors for developing MS, as they designed the study to assess the impact of active treatment vs placebo.
Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Lebrun-Frénay C, Siva A, Sormani MP, et al. Teriflunomide and time to clinical multiple sclerosis in patients With radiologically isolated syndrome: the TERIS randomized clinical trial. JAMA Neurol. Published online August 23, 2023. doi:10.1001/jamaneurol.2023.2815