Comparative efficacy, safety, and number needed to treat analysis of atogepant and rimegepant for the preventive treatment of episodic migraine in Japanese participants: An indirect comparison analysis

Background In the absence of head-to-head analyses, indirect treatment comparisons (ITCs) can be used for comparative treatment evaluations. A previous ITC of atogepant and rimegepant assessed outcomes from US trials for the preventive treatment of migraine. We expand those initial analyses, and use an ITC to evaluate the efficacy, safety, and tolerability, and estimate the number needed to treat (NNT) per additional ≥50% responder for atogepant and rimegepant in Japanese participants. Methods RELEASE (M22-056) and BHV3000-309 were randomized, double-blind, placebo-controlled studies evaluating atogepant compared with placebo and rimegepant compared with placebo for the preventive treatment of episodic migraine (EM) in Japanese participants, respectively. An ITC using a random effects model compared the efficacy, safety, and tolerability of atogepant 60 mg once daily and rimegepant 75 mg once every other day. Estimates of mean differences with 95% confidence intervals (CIs) are presented for monthly migraine days (MMDs), acute medication use days, Migraine-Specific Quality of Life Questionnaire v2.1 (MSQ v2.1) Role Function-Restrictive (RFR) domain score, Migraine Disability Assessment (MIDAS), and European Quality of Life Visual Analog Scale (EQ VAS). Safety and tolerability results are presented as hazard ratios and 95% CIs. The NNT resulting in one additional person achieving a ≥ 50% reduction from baseline in mean MMDs/monthly headache days was analyzed across three responder definitions. Results Atogepant demonstrated significantly higher mean monthly acute medication use days reduction (−1.68, 95% CI: −2.72 to −0.64; P < 0.002) at weeks 1 to 12 and significantly greater improvement in MSQ v2.1 RFR domain score (5.13, 95% CI: 1.10 to 9.16; P = 0.01) at week 12. Additionally, atogepant demonstrated numerically higher mean MMD reduction at weeks 1 to 12, numerically greater reduction (improvement) in MIDAS at week 12, and numerically lower improvement in EQ VAS at week 12 relative to rimegepant (all P > 0.05). Atogepant demonstrated numerically lower likelihood of treatment-emergent adverse events (TEAEs) (0.70, 95% CI: 0.45 to 1.09) and adverse events (AEs) leading to discontinuation (0.50, 95% CI: 0.03 to 9.46) compared with rimegepant (both P > 0.05). The median NNT (95% CI) versus placebo for a ≥ 50% reduction from baseline in mean MMDs across weeks 1 to 12 was 2.5 (1.9 to 4.1) for atogepant and 16.6 (6.7 to ∞) for rimegepant. Additional responder definitions were consistent. Conclusions Among Japanese participants with EM, atogepant 60 mg demonstrated significantly or numerically greater improvements in four of five efficacy outcomes and numerically lower TEAEs and AEs leading to discontinuation compared with rimegepant 75 mg. Atogepant 60 mg had substantially lower NNTs per additional ≥50% responder versus placebo than rimegepant 75 mg. Trial Registrations: These studies are registered with ClinicalTrials.gov (NCT05861427, NCT05399485).