Teriflunomide prevents conversion to MS in patients with RIS

In patients with a radiologically isolated syndrome (RIS), treatment with teriflunomide resulted in a 72% adjusted risk reduction compared with a placebo for a first clinical event related to the central nervous system (CNS) in the phase 3 TERIS study. These outcomes add evidence for the benefit of early intervention with disease-modifying treatment (DMT) in the demyelinating spectrum of multiple sclerosis (MS).

RIS represents the earliest detectable pre-clinical phase of MS. MRI features of patients with RIS are highly similar to MS, but patients do not present with clinical symptoms yet. In the previously published phase 3 ARISE trial (NCT02739542), the use of dimethyl fumarate was associated with a risk reduction for the clinical onset of MS of >80% [1]. The current phase 3 TERIS study (NCT03122652) aimed to evaluate the efficacy and safety of the DMT teriflunomide, which has a different mechanism of action from dimethyl fumarate, in a cohort of participants with RIS from Europe and Turkey [2]. First author Prof. Christine Lebrun-Frenay (Centre Hospitalier Universitaire de Nice, France) presented the results.

The TERIS study included 89 participants aged 18 or older who fulfilled the 2009 RIS criteria. Participants were randomised 1:1 to teriflunomide (14 mg daily) or a placebo. The primary outcome measure was the time-to-onset of the first clinical symptom attributed to a CNS demyelinating event over 96 weeks. Of the randomised participants, 63 (71%) were women, the mean age was 40 years, and the age at index MRI was 38.

During 96 weeks of follow-up, 28 clinical events were detected: 8 in the teriflunomide and 20 in the placebo group. This difference was significant in both the unadjusted (HR 0.37) and adjusted analysis (HR 0.28; see Figure).

Figure: Primary endpoint analysis: risk of a first demyelinating event [2]



Though not statistically significant, the number of new T2 and gadolinium-enhancing brain MRI lesions and PROs exploratory outcomes (i.e., cognition, quality of life, and fatigue) was also lower in the treatment group than in the placebo group. For the cumulative number of Gd+ lesions, the adjusted rate ratio (RR) was 0.33 (95% CI 0.09–1.37; P=0.086). For new or enlarging T2 lesions, the adjusted RR was 0.57 (95% CI 0.27–1.20; P=0.139). Prof. Lebrun-Frenay added that the observed safety profile was consistent with known outcomes reported in prior pivotal studies of teriflunomide.

1. Okuda DT, et al. Ann Neurol. 2023;93(3):604–614.
2. Lebrun-Frenay C, et al. Teriflunomide (Aubagio) extends the time to multiple sclerosis in radiologically isolated syndrome: The TERIS study. ES2.010, AAN 2023 Annual Meeting, 22–27 April, Boston, USA.

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Posted on 26 June 2023