The TERIS trial of teriflunomide in individuals with radiologically isolated syndrome (RIS) has reported that treatment significantly prolonged the time to a first clinical event by 63% versus placebo (Lebrun-Frenay et al. JAMA Neurol, epublished August 21, 2023).
The study randomized 89 individuals with RIS to teriflunomide 14 mg/day or placebo for 96 weeks. Mean age was 37.9 years. The most common reason for an MRI was headache (41%). A total of 28.1% had Gd+ lesions and 44.9% had spinal cord lesions at entry.
A total of eight clinical events occurred in the teriflunomide group compared to 20 in the placebo group. The mean time to a first clinical event was 128.2 weeks versus 109.6 weeks, respectively (unadjusted hazard ratio 0.37). Two progressive events (cognitive impairment, progressive paraparesis) occurred in both groups. There was also no significant treatment benefit with respect to MRI endpoints (cumulative number of new/enlarging T2 or Gd+ lesions), cognition or patient-reported outcomes (fatigue, quality of life).
The study was terminated early due to slow recruitment and withdrawal of financial support due to the imminent arrival of generic teriflunomide.
While the results support the treatment of RIS in selected circumstances, the authors cautioned about the risk of misdiagnosing RIS in individuals with nonspecific MRI findings. Indeed, 15% of those screened failed to meet diagnostic criteria. It should also be noted that a majority of RIS cases, including those with spinal cord lesions and positive CSF, will not experience a clinical event in the first five years (Lebrun-Frenay et al. Brain 2023;146:3431-3443). The estimated 10-year risk of a clinical event in an RIS cohort is 51.2% (Lebrun-Frenay et al. Ann Neurol 2020;88:407-417).
TERIS is the second published RIS treatment trial. In the ARISE study (N=87), dimethyl fumarate 240 mg BID significantly reduced the risk of a first demyelinating event versus placebo (HR 0.18) in older individuals with RIS (mean age 44.2 years) (Okuda et al. ) That study was also terminated early.