BOSTON – , according to a double-blind, phase 3 trial presented in the Emerging Science session of the 2023 annual meeting of the American Academy of Neurology.
“These data add to the evidence that early immunomodulation offers clinical benefit even in the presymptomatic phase of MS,” reported Christine Lebrun-Frenay, MD, PhD, head of inflammatory neurological disorders research unit, University of Nice, France. This is the second study to show a benefit from a disease-modifying therapy in asymptomatic RIS patients. The ARISE study, which was presented at the 2022 European Committee for Treatment and Research in MS and has now been published, compared 240 mg of twice-daily dimethyl fumarate with placebo. Dimethyl fumarate was associated with an 82% (hazard ratio, 0.18; P = .007) reduction in the risk of a first demyelinating event after 96 weeks of follow-up.
TERIS trial data
In the new study, called TERIS, the design and outcomes were similar to the ARISE study. Eighty-nine patients meeting standard criteria for RIS were randomized to 14 mg of once-daily teriflunomide or placebo. The majority (71%) were female, and the mean age was 39.8 years. At the time of RIS diagnosis, the mean age was 38 years. At study entry, standardized MRI studies were performed of the brain and spinal cord.
During 2 years of follow-up, 8 of 28 demyelinating events were observed in the active treatment group. The remaining 20 occurred in the placebo group. This translated to a 63% reduction (HR, 0.37; P = .018) in favor of teriflunomide. When graphed, the curves separated at about 6 months and then widened progressively over time.
Distinct from clinically isolated syndrome (CIS), which describes individuals who have a symptomatic episode consistent with a demyelinating event, RIS is based primarily on an MRI that shows lesions highly suggestive of MS. Neither confirms the MS diagnosis, but both are associated with a high likelihood of eventually meeting MS diagnostic criteria. The ARISE and TERIS studies now support therapy to delay demyelinating events.
“With more and more people having brain scans for various reasons, such as headache or head trauma, more of these cases are being discovered,” Dr. Lebrun-Frenay said.
Caution warranted when interpreting the findings
The data support the theory that treatment should begin early in patients with a high likelihood of developing symptomatic MS on the basis of brain lesions. It is logical to assume that preventing damage to the myelin will reduce or delay permanent symptoms and permanent neurologic impairment, but Dr. Lebrun-Frenay suggested that the available data from ARISE and TERIS are not practice changing even though both were multicenter double-blind trials.
“More data from larger groups of patients are needed to confirm the findings,” she said. She expressed concern about not adhering to strict criteria to diagnosis RIS.
“It is important that medical professionals are cautious,” she said, citing the risk of misdiagnosis of pathology of MRI that leads to treatment of patients with a low risk of developing symptomatic MS.
Teriflunomide and dimethyl fumarate, which have long been available as first-line therapies in relapsing-remitting MS, are generally well tolerated. In the TERIS and ARISE studies, mild or moderate events occurred more commonly in the active treatment than the placebo arms, but there were no serious adverse events. However, both can produce more serious adverse events, which, in the case of teriflunomide, include liver toxicity leading to injury and liver failure.