Remarkable Findings from the Subanalysis of the Efficacy and Safety of Teriflunomide in the Chinese Population with MS in Relation to Global Results

Evaluated Patient Population

A total of 1165 patients aged 18–55 years with diagnosed relapsing MS, who had an EDSS (Expanded Disability Status Scale) score ≤ 5.5, were included in the study. The study also included a subgroup of Chinese patients.

Participants were randomized into 3 groups in a 1:1:1 ratio to receive either 7 mg or 14 mg teriflunomide or a placebo. The Chinese subgroup consisted of 148 patients, of whom 54 received a placebo, 51 received the lower dose of teriflunomide, and 43 received the higher dose of teriflunomide.

Monitored Parameters and Goals

The primary goal was to assess the efficacy of both doses compared to the placebo in terms of reducing the number of relapses over one year. Efficacy was expressed as the annualized relapse rate (ARR). The secondary goal was to assess the efficacy of both doses compared to the placebo based on confirmed disability worsening over 12 weeks (CDW). Safety and tolerability of the drug were also monitored.

Findings in the Chinese Cohort

Efficacy

In the placebo group, the ARR was 0.63 (95% confidence interval [CI] 0.44–0.92), in the 7 mg teriflunomide group it was 0.48 (95% CI 0.33–0.70), and in the 14 mg teriflunomide group it was 0.18 (95% CI 0.09–0.36). This corresponded with a significant reduction in the risk of relapse in the higher dose teriflunomide group compared to the placebo (by 71.2%; p = 0.0012). Teriflunomide at this dose also reduced CDW by 68.1% compared to the placebo (hazard ratio [HR] 0.319; p = 0.1184).

It is noteworthy that teriflunomide demonstrated numerically higher efficacy in the Chinese subpopulation than in the overall population. In the 14 mg teriflunomide group, ARR decreased by 71.2% in Chinese patients, while in the overall population it was 36.3%. CDW was also significantly reduced in the Chinese subpopulation compared to the overall population. Genetic polymorphisms in genes for efflux transporters in Asian patients, leading to slightly increased concentrations of teriflunomide in blood plasma and thus increased drug exposure, may have contributed to the higher effect. The Chinese subgroup also had a shorter duration since MS diagnosis compared to the overall population, which may suggest benefits of early treatment.

Safety Profile

There were no significant differences in the proportion of patients with adverse events (AEs) during treatment among the groups. The incidence of serious treatment-related AEs was similar in the placebo and 14 mg teriflunomide groups (11.1% and 11.6%, respectively), and significantly lower in the 7 mg teriflunomide group (3.9%). Adverse events that led to treatment discontinuation occurred more frequently in patients treated with teriflunomide than in the placebo group.

The most common treatment-related AEs included neutropenia, elevated alanine aminotransferase levels, and hair loss. The placebo group reported nasopharyngitis, urinary tract infections, constipation, and itching.

Conclusion

Teriflunomide demonstrated good efficacy, safety, and tolerability in the overall patient population in the TOWER study. In the Chinese patient subgroup, its efficacy was numerically higher than in the overall population. The best risk-benefit ratio was achieved with the 14 mg dose of teriflunomide, both in the Chinese subgroup and in the overall population.

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Source: Qiu W., Huang D.-H., Hou S.-F. et al. Efficacy and safety of teriflunomide in Chinese patients with relapsing forms of multiple sclerosis: a subgroup analysis of the phase 3 TOWER study. Chin Med J (Engl) 2018; 131 (23): 2776–2784, doi: 10.4103/0366-6999.246067.