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Early Intervention With Teriflunomide May Delay Multiple Sclerosis in Some Individuals
For individuals with radiologically isolated syndrome (RIS), early intervention with teriflunomide may prevent the time to development of multiple sclerosis (MS) by as much as 63%. Findings from the TERIS randomized clinical trial were published in JAMA Neurology.
“The MS community now has 2 multicenter, placebo-controlled, double-blind, randomized clinical trials showing that active treatment extends the time to symptomatic MS in people with RIS, fulfilling a previously unmet need,” wrote Christine Lebrun-Frénay, MD, PhD, FAAN, Inflammatory Neurological Disorders Clinical Research Unit, Nice University Hospital, France, and co-authors. “Earlier treatment during the presymptomatic phase of MS may delay disability outcomes even further than treatment after symptomatic MS onset.”
The multicenter, double-blind, phase 3, randomized clinical trial assessed 124 potential participants older than 18 years who met the 2009 criteria for RIS. Eligible individuals were randomly assigned 1:1 to receive either oral teriflunomide, 14 mg daily, or placebo up to week 96 or, if chosen, to week 144. The primary outcome under investigation was the “time to a first acute or progressive neurological event resulting from [central nervous system] demyelination” resulting in clinical MS. Secondary outcomes were assessed through brain MRI metrics, including new and/or growing T2-weighted hyperintense lesions and new gadolinium-enhancing (Gd+) lesions.
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Ultimately, 89 participants (mean [SD] age, 37.8 [12.1] years; 63 female [70.8%]) were enrolled (placebo, 45 [50.6%]; teriflunomide, 44 [49.4%]) in the study. Of those, 18 participants (placebo, 9 [50.0%]; teriflunomide, 9 [50.0%]) discontinued the study, resulting in a dropout rate of 20% for adverse events (3 [16.7%]), consent withdrawal (4 [22.2%]), loss to follow-up (5 [27.8%]), voluntary withdrawal (4 [22.2%]), pregnancy (1 [5.6%]), and study termination (1 [5.6%]).
The time to the first clinical event was significantly extended in the teriflunomide arm compared with placebo, in both the unadjusted (hazard ratio [HR], 0.37; 95% CI, 0.16-0.84; P = .02) and adjusted (HR, 0.28; 95% CI, 0.11-0.71; P = .007) analysis. Secondary imaging end point outcomes including the comparison of the cumulative number of new or newly enlarging T2 lesions (rate ratio [RR], 0.57; 95% CI, 0.27-1.20; P = .14), new Gd+ lesions (RR, 0.33; 95% CI, 0.09-1.17; P = .09), and the proportion of participants with new lesions (odds ratio, 0.72; 95% CI, 0.25-2.06; P = .54) were not significant.
The most common adverse effects reported by study participants were gastrointestinal disorders, dysmenorrhea, benign respiratory infections, general disorders/conditions, and transient increase of transaminases.
“The choice between oral [disease-modifying therapies] will depend on the patient discussion, especially in young women, where pregnancy planning may be required as teriflunomide requires a strict washout period,” the authors wrote in the study conclusion. “However, before considering any immune intervention, it is essential to highlight the risk of misdiagnosing individuals with nonspecific MRI anomalies as having RIS, underscoring the role of MS tertiary centers in accurately classifying and managing such individuals.”
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