Teriflunomide vs. Dimethyl Fumarate in Real Practice: We Know the Winner! Will It Surprise You?
Teriflunomide and dimethyl fumarate are disease-modifying drugs (DMDs) used in the treatment of multiple sclerosis (MS). Regarding the course, form, and severity of MS, their target groups are comparable in their characteristics. These DMDs are therefore ideal candidates for mutual comparison. Swedish authors decided to compare their effectiveness based on data from real clinical practice obtained through the Swedish National Registry.
Mechanism of Action
Teriflunomide is a DMD with anti-inflammatory effects. It selectively and reversibly inhibits the mitochondrial enzyme dihydroorotate dehydrogenase. As a result of inhibition, it generally reduces the proliferation of rapidly dividing cells that depend on de novo pyrimidine synthesis required for growth. The exact mechanism underlying the therapeutic effect of teriflunomide in MS is not entirely known, but it is based on reducing the number of lymphocytes.
The mechanism of the therapeutic effect of dimethyl fumarate is also not fully understood. Its pharmacodynamic action is likely primarily triggered by the activation of the Nrf2 (nuclear factor erythroid 2-related factor 2) transcription pathway. Dimethyl fumarate in MS patients has been shown to induce up-regulation of Nrf2-dependent antioxidant genes.
Evaluated Parameters and Patient Population
All patients with relapsing-remitting MS (RRMS) who started therapy with teriflunomide or dimethyl fumarate in Sweden between 2000 and 2019 were included in the study. The primary evaluated parameter was persistence on therapy. Also evaluated were the time to the first relapse, annual relapse rate, confirmed improvement in condition, and disability progression assessed using the Kurtzke scale (EDSS − Expanded Disability Status Scale). Using the propensity score matching method, a total of 353 patients treated with teriflunomide were compared with 353 patients using dimethyl fumarate.
Results
No significant difference was noted between the two groups in terms of persistence on therapy (hazard ratio [HR] 1.12; 95% confidence interval [CI] 0.91–1.39; p = 0.277; relative to teriflunomide). The annual relapse rate was also comparable (p = 0.237) between patients treated with dimethyl fumarate (0.07; 95% CI 0.05–0.10) and teriflunomide (0.09; 95% CI 0.07–0.12). There were no significant differences in time to first relapse (HR 0.78; 95% CI 0.50–1.21), disability progression (HR 0.55; 95% CI 0.27–1.12), or confirmed improvement in condition (HR 1.17; 95% CI 0.57–2.36).
Conclusion
The battle between teriflunomide and dimethyl fumarate ended in a draw. Data from real clinical practice show that persistence on therapy, annual relapse rate, time to first relapse, confirmed improvement in condition, and disability progression are comparable in patients treated with these two DMDs. The real winners of this match are mainly the patients themselves, as they can benefit from the current options of disease-modifying treatment for MS.
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Source: Hillert J., Tsai J.A., Nouhi M. et al. A comparative study of teriflunomide and dimethyl fumarate within the Swedish MS Registry. Mult Scler 2021 Jun 3: 13524585211019649, doi: 10.1177/13524585211019649 [Epub ahead of print].
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