Did the Extension of the TOWER Study Confirm the Position of Teriflunomide?

Introduction

Teriflunomide is an oral immunomodulatory drug developed for long-term therapy in relapsing-remitting multiple sclerosis (RRMS). It is an inhibitor of the enzyme dihydroorotate dehydrogenase, which inhibits the proliferation of autoreactive B and T lymphocytes. This cytostatic effect and mechanism of action is specific and unique.

Teriflunomide demonstrated its ability to positively influence disease progression in the TOWER study, where a daily dose of 14 mg resulted in a reduction of the annual relapse rate and a decrease in the risk of 12-week confirmed progression. Do these findings hold true in the extension of the aforementioned study? And do we have new insights into the safety profile of teriflunomide?

Characteristics of the Study Population

The TOWER study extension involved 751 patients. These were divided into 3 groups: 253 patients took a placebo during the TOWER study and then 14 mg teriflunomide in the extension, 265 took 7 mg teriflunomide followed by 14 mg, and 233 took 14 mg throughout. The median duration of use was 4.25 years (maximum 6.3 years). A total of 202 patients discontinued therapy during the extension for various reasons (insufficient effect, non-compliance, side effects, etc.).

Effectiveness of the Treatment

The risk of 12-week confirmed progression was lower in patients in the 7 mg/14 mg and 14 mg/14 mg groups compared to patients switching to teriflunomide from placebo.

There was also a significant reduction in the annual relapse rate in the 14 mg/14 mg group compared to the placebo/14 mg group.

The Kurtzke Expanded Disability Status Scale (EDSS) score remained unchanged during the extension in all groups.

Safety Profile

The incidence of adverse events was, as expected, highest in the 14 mg/14 mg group. Infections occurred in 38.6% of patients in the placebo/14 mg group, 46.1% in the 7 mg/14 mg group, and 48.5% in the 14 mg/14 mg group during the extension. The most commonly reported were urinary tract infections, nasopharyngitis, and influenza.

An elevation in alanine aminotransferase (ALT) occurred more frequently in patients who switched to 14 mg teriflunomide from placebo, compared to those who switched from 7 mg or who were on 14 mg from the original study.

The incidence of adverse events of special interest (hematologic adverse effects, hepatopathies, peripheral neuropathy, hypertension, and malignancies) was generally low and comparable across all groups.

Conclusion

The extension of the TOWER study confirmed the efficacy of 14 mg teriflunomide for patients with RRMS. With its favorable safety profile and effectiveness, this drug represents a promising therapeutic option for patients with multiple sclerosis.

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Source: Miller A. E., Olsson T. P., Wolinsky J. S. et al.; TOWER investigators. Long-term safety and efficacy of teriflunomide in patients with relapsing multiple sclerosis: results from the TOWER extension study. Mult Scler Relat Disord 2020 Aug 1; 46: 102438, doi: 10.1016/j.msard.2020.102438.