Singh, Rashmi B. Halker

Background To evaluate the benefit-risk assessment of atogepant and calcitonin gene–related peptide (CGRP) monoclonal antibodies (mAbs) vs. placebo based on the number needed to treat (NNT) and the number needed to harm (NNH) in a blended episodic migraine and chronic migraine (EM + CM) population. Methods The NNT was calculated based on achievement of a ≥ 50% reduction in mean monthly migraine days (MMDs) from baseline across 12 weeks. The NNH was calculated using the proportion of participants reporting a discontinuation due to adverse events (AEs). The primary analysis included data from studies of atogepant, erenumab, galcanezumab, eptinezumab and fremanezumab. Results In the primary analysis, the calculated NNT for atogepant 60 mg vs. placebo was 4.2 (95% credible interval (CrI) = 3.1–6.7), which was the lowest relative to the CGRP mAbs in the blended EM + CM population. Participants who received atogepant 60 mg or fremanezumab showed the most favorable NNH values (−1010 (95% Crl = 44 to ∞ to number needed to benefit 80) for atogepant) resulting from lower rates of discontinuation due to AEs compared with those receiving placebo. Conclusions Atogepant demonstrated a favorable benefit-risk profile, with NNT and NNH values comparable (not statistically significant) with those of CGRP mAbs across all analyses.

Abstract Objective To estimate the number needed to treat and cost per additional responder for atogepant and rimegepant versus placebo for the preventive treatment of episodic migraine (EM) in the United States. Background Migraine has an enormous impact on a person's daily activities and quality of life, and results in significant clinical and economic burden to both individuals and society. It is important to understand the comparative efficacy and economic value of oral calcitonin gene–related peptide receptor antagonists (gepants) for preventive treatment of EM. Currently, atogepant and rimegepant are US Food and Drug Administration approved for preventive treatment of migraine (rimegepant for EM and atogepant for EM and for chronic migraine). In the absence of head‐to‐head trials, we utilized an indirect treatment comparison on efficacy data from clinical trials conducted for the preventive treatment of EM. We estimated number needed to treat, a valuable metric used in clinical practice to compare treatment efficacy, and cost per additional responder, which can be used to establish the cost effectiveness of a treatment. Methods An indirect treatment comparison was conducted to compare the efficacy of atogepant 60 mg once daily and rimegepant 75 mg once every other day as preventive treatments for EM using published data from the registrational trials of atogepant (ADVANCE) and rimegepant (BHV3000‐305). The efficacy outcome of interest was ≥50% reduction from baseline in mean monthly migraine/headache days (≥50% responder rate), which was variably defined for a base case and two scenario analyses. Number needed to treat and cost per additional responder versus placebo were calculated and compared between both treatments (weeks 9–12 in the base case analysis; weeks 1–12 and 9–12 for atogepant and during weeks 9–12 for rimegepant in the scenario analyses). Results In the base case analysis, ≥50% responder rates were 64.9% (95% confidence interval [CI], 53.9–74.5) for atogepant and 51.8% (95% CI, 42.9–60.6) for rimegepant, compared to 44.1% (95% CI, 39.4–49.0) for placebo. The median number needed to treat versus placebo in the base case scenario was 4.8 (95% CI, 3.1–9.0) for atogepant compared to 13.0 (95% CI, 5.9–75.1) for rimegepant. The cost per additional responder versus placebo in the base case scenario was estimated to be $15,823 (95% CI, $11,079–$29,516) for atogepant compared to $73,029 (95% CI, $32,901–$422,104) for rimegepant. Results of the two scenario analyses were consistent with the base case analysis. Conclusions Atogepant had substantially lower numbers needed to treat and costs per additional responder versus placebo than rimegepant for the preventive treatment of EM across all evaluated scenarios. These analyses suggest that atogepant may be more cost effective than rimegepant for the preventive treatment of EM. Limitations include differences in inclusion/exclusion criteria and in reporting of the ≥50% responder rates between trials.

Background Comparative evaluations of preventive migraine treatments can help inform clinical decision making for managing migraine in clinical practice. Methods An anchored matching-adjusted indirect comparison analysis was conducted using pooled participant-level data from two phase 3 atogepant trials (ADVANCE and PROGRESS) and one phase 2/3 rimegepant trial (BHV3000-305) to evaluate the relative efficacy and safety/tolerability of atogepant and rimegepant as preventive migraine treatments. Participants receiving atogepant 60 mg once daily, rimegepant orally disintegrating tablet 75 mg once every other day, and placebo were included. Only participants meeting the BHV3000-305 inclusion/exclusion criteria were analyzed: ≥6 monthly migraine days and ≤18 monthly headache days at baseline. The primary efficacy assessment of interest was change in monthly migraine days across weeks 1–12. Results There were 252 participants in the atogepant group and 348 in the rimegepant group. Across weeks 1–12, atogepant 60 mg demonstrated a significantly greater reduction in mean monthly migraine days compared with rimegepant 75 mg (mean difference [95% CI]: −1.65 [−2.49, −0.81]; p < 0.001). Both atogepant and rimegepant demonstrated similar safety/tolerability profiles. Conclusion In this matching-adjusted indirect comparison analysis, oral atogepant 60 mg once daily demonstrated a significantly greater reduction in monthly migraine days compared with rimegepant 75 mg orally disintegrating tablet once every other day.