Summary

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• Mayzent (siponimod) is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
• This summary is based on the review of seven systematic reviews/meta-analyses. ^[1-7]
• Effectiveness in Progressive MS (PMS): Disease-modifying therapies (DMTs) such as mitoxantrone, siponimod, and ocrelizumab effectively delay disease progression. Mitoxantrone is particularly effective in mitigating disability progression, while ocrelizumab and natalizumab perform best in functional performance tests (T25FW and 9HPT, respectively).
• Relapse Reduction and Disability Mitigation in RRMS: Alemtuzumab, mitoxantrone, natalizumab, and fingolimod are the most effective in reducing relapse frequency in relapsing-remitting multiple sclerosis (RRMS). Mitoxantrone, alemtuzumab, and natalizumab are also highly effective in preventing disability worsening.
• Comparative Efficacy in Relapsing MS (RMS): Alemtuzumab shows the highest efficacy in reducing the annualized relapse rate, while ofatumumab is most effective in reducing disability progression. Interferon beta-1b has the best safety profile for serious adverse events (SAEs).
• Rituximab and laquinimod show a better safety profile compared to placebo in minimizing adverse events (AEs), while natalizumab and ocrelizumab are associated with a lower incidence of serious adverse events (SAEs) compared to placebo.
• Siponimod has been linked to an increased risk of cardiovascular AEs, particularly bradyarrhythmia and hypertension, and common AEs include headache, back pain, and upper respiratory tract infections; there is limited evidence on serious adverse events (SAEs) for siponimod, with no significant difference from placebo.
• Pharmacogenetic Considerations: Genetic variants in CYP2C9 significantly impact the metabolism of siponimod, necessitating genetic testing before treatment. Siponimod is contraindicated in patients with the CYP2C9 *3/*3 genotype, and patients with CYP2C9 *1/*3 or *2/*3 genotypes require dose adjustments due to reduced metabolic rates, with potential long-term safety implications for poor metabolizers.