Teriflunomide Delays MS Progression in Patients With Radiologically Isolated Syndrome

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.

The mean (SD) age for the combined groups was 37.8 (12.1), with 63 women (70.8%) and 26 men participants (29.2%).

The baseline demographic and clinical data of the participants were evenly distributed across the groups.

The researchers collected clinical, MRI, and patient-reported outcomes data at baseline and annually for 96 weeks with an optional third year if no symptoms had arisen.

Eighteen participants, evenly distributed between the placebo (9 [50.0%]) and teriflunomide (9 [50.0%]) groups, withdrew from the study, resulting in a dropout rate of 20% due to:

• 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%]).

Out of 28 primary clinical endpoints, 4 (14.3%) indicated primary progressive MS, whereas 24 (85.7%) were acute relapses. Acute events were localized in various areas, including the:

• 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%]).

Progressive events included cognitive impairment (2 [7.2%]) and progressive paraparesis (2 [7.2%]). The mean (SD) time until the occurrence of the first clinical event was 119 (5.2) weeks.

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%).

Only 1 patient discontinued the study as a result of AEs.

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.

“Earlier treatment during the presymptomatic phase of MS may delay disability outcomes even further than treatment after symptomatic MS onset,” the researchers concluded.

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.