Tailored Treatment. Who is Teriflunomide Suitable For?
The authors of the recently published study cited below not only focused on the safety and efficacy of teriflunomide in real-world clinical practice but also on the risk factors for its insufficient effectiveness. Who is teriflunomide most suitable for, and when should alternatives be considered?
Ambitious Goals for MS Treatment
Multiple sclerosis (MS) is a chronic autoimmune-mediated disease of the central nervous system. Although it is not curable, it is quite treatable. Especially in the past two decades, there has been a rapid development in therapeutic options for MS, and for this reason, the bar for treatment goals is set higher and higher. The currently widely accepted goal is the concept of NEDA-3 (No Evidence of Disease Activity 3). It is defined by the absence of relapses, progression on the EDSS (Expanded Disability Status Scale) scale, and new lesions on magnetic resonance imaging (MRI).
One of the disease-modifying drugs (DMDs) used in the treatment of relapsing-remitting MS (RRMS) is teriflunomide, an oral medication administered once daily. It affects the disease by reducing the proliferation of activated T and B lymphocytes through inhibition of mitochondrial respiration via dihydroorotate dehydrogenase inhibition. The efficacy of teriflunomide has already been demonstrated in clinical trials. However, the authors of the cited study focused on its efficacy and safety in real-world clinical practice, which differs from ideal study conditions in many criteria. As a measure of efficacy, they chose the already mentioned concept of NEDA-3. Who is teriflunomide suitable for, and which patients are at a higher risk of therapy failure?
Study Methodology
This prospective observational cohort study from real-world clinical practice included a total of 217 RRMS patients on teriflunomide therapy. Using a multivariate Cox proportional hazards regression model, risk factors for therapy failure were identified.
Results
For 82% of the observed patients, teriflunomide was the first DMD used. After one year of treatment, 79% of the subjects achieved NEDA-3 status. Furthermore, there was a significant reduction in annual relapse rate (ARR; from 0.79 ± 0.80 to 0.16 ± 0.70; p < 0.001), and the average EDSS value did not significantly change compared to baseline values (1.40 ± 1.67 vs. 1.56 ± 1.88; p > 0.05).
Risk factors for not achieving NEDA-3 status were:
- Male gender (hazard ratio [HR] 1.856; 95% confidence interval [CI] 1.118–3.082; p < 0.05)
- Baseline EDSS ≥ 4 (HR 2.682; 95% CI 1.375–5.231; p < 0.01)
- Higher frequency of relapses before treatment (HR 3.056; 95% CI 1.737–5.377; p < 0.01)
The occurrence of adverse events was consistent with the occurrence in original studies. The most common were hair thinning, elevated alanine aminotransferase (ALT), and leukopenia. The latter two adverse events were also the most common reasons for discontinuing teriflunomide therapy. The persistence rate on therapy was 86.9% after 6 months, 72.4% after 1 year, and 52.8% after 24 months.
Conclusion
The conclusions of this study confirm the safety and efficacy of teriflunomide in real-world clinical practice. They show that the greatest benefit from this DMD is likely to be seen in previously untreated women with a smaller number of relapses in history and a lesser degree of neurological impairment before starting treatment.
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Source: Zhang Y., Yin H., Zhang D. et al. Real-world outcomes of teriflunomide in relapsing-remitting multiple sclerosis: a prospective cohort study. J Neurol 2022 Sep; 269 (9): 4808–4816, doi: 10.1007/s00415-022-11118-7.
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