Objective:

Evaluate the benefit-risk assessment of atogepant and calcitonin gene– related peptide (CGRP) monoclonal antibodies (mAbs) vs placebo based on number needed to treat (NNT) and number needed to harm (NNH) in a blended episodic and chronic migraine population (EM+CM).

Background:

Atogepant is a calcitonin gene-related peptide (CGRP) receptor antagonist approved in the U.S. for the preventive treatment of migraine in adults.

Design/Methods:

The NNT was calculated based on achievement of a ≥50% reduction in mean monthly migraine days (MMDs) from baseline across 12 weeks. A random effects model was used in the meta-analysis of trials to calculate the median ≥50% response rates, NNTs, and credible intervals (CrI) versus placebo at 12 weeks. The NNH was calculated using the proportion of participants reporting a discontinuation due to adverse events (AEs). A cloglog link model was used to estimate median discontinuation rates due to AEs at 12 weeks and calculate NNH and CrI. The base-case analysis included data from core studies of atogepant 60 mg, erenumab 70 mg and 140 mg, galcanezumab 120 mg, eptinezumab 100 mg and 300 mg, and fremanezumab 225 mg and 675 mg. Additional scenario analyses were conducted, including dose-response relationship studies, Asian studies, and dedicated inadequate prior treatment studies (only for NNH).

Results:

Based on the base-case scenario, the calculated NNT for atogepant 60 mg vs placebo was 4.2, which was comparable with CGRP mAbs in the blended EM+CM population. Participants who received atogepant 60 mg or fremanezumab (225 mg or 675 mg) demonstrated lower rates of discontinuation due to AEs compared with those receiving placebo, resulting in negative NNH values. Comparable NNT and NNH values were observed for atogepant 60 mg relative to the mAbs across all scenario analyses.

Conclusions:

Atogepant demonstrated a favorable benefit-risk profile, with NNT and NNH values comparable with those of CGRP mAbs across all scenarios.