To evaluate the relative efficacy of rimegepant, atogepant, and monoclonal antibody (mAb) treatments for the prevention of migraine.

Novel treatments that antagonize calcitonin gene-related peptide activity have demonstrated efficacy and safety for the preventive treatment of migraine. These include the small molecule oral gepants and injectable mAbs. None of these therapies have been compared in head-to-head trials.

A comprehensive systematic literature review was conducted in MEDLINE and Embase. Efficacy was compared via network meta-analyses. The evidence base consisted of placebo-controlled trials in patients with episodic migraine, for FDA approved doses of the following treatments: rimegepant, atogepant, erenumab, galcanezumab, eptinezumab, and fremanezumab. Change in MMDs was measured from baseline to 12-weeks, while number achieving a ≥50% reduction in baseline MMDs employed a binomial likelihood and cloglog link model (assuming constant event rates over the trial durations) to account for differing reporting times.

For change in MMDs and number achieving a ≥50% reduction in baseline MMDs, significantly favorable differences were seen for active treatments vs. placebo. Due to a sparse network of evidence, fixed-effects models were utilized. Results for change in MMDs vs placebo ranged from eptinezumab 100mg (mean difference -0.71 MMDs [95% credible interval; -1.27,-0.13]) to erenumab 140mg (-1.77[-2.31,-1.23]) for the mAbs and are as follows for the oral treatments: rimegepant 75mg (-0.90[-1.47,-0.33]), atogepant 10mg (-1.09[-1.53,-0.64]), atogepant 30mg (-1.13[-1.53,-0.72]), atogepant 60mg (-1.19[-1.58,-0.78]). For number achieving a 50% reduction in baseline MMDs, estimates vs placebo ranged from eptinezumab 100mg (hazard ratio 1.47 [95% credible interval; 1.10, 1.97]) to erenumab 140mg (2.05[1.60,2.60]) for the mAbs, and are as follows for the oral treatments: rimegepant 75mg (1.53[1.21,1.96]), atogepant 10mg (1.98[1.58,2.50]), atogepant 30mg (2.00[1.61,2.48]), atogepant 60mg (2.02[1.63,2.50]).

Rimegepant, atogepant, and mAbs were all effective treatment options for the prevention of migraine when compared vs placebo and generally showed similar effects when compared to one another.