Rationale for Correct Answer

The correct answer is: Yes, because current evidence suggests combining gepants with anti-CGRP monoclonal antibodies is safe and can be effective in managing breakthrough migraines

The data from modeling ligand-targeting CGRP monoclonal antibodies indicate that CGRP plasma levels exhibit a pattern of initial decrease followed by an increase within a month. Up to 36% to 55% of CGRP is still circulating freely during this time frame. This finding supports the potential therapeutic advantages of adding a gepant to a CGRP monoclonal to achieve additional treatment benefits.1

Evidence from 2 case studies demonstrates the absence of significant treatment emergent adverse events when combining rimegepant with erenumab.2 Similarly, small studies investigating the coadministration of rimegepant or ubrogepant with anti-CGRP monoclonal antibodies have reported no serious adverse events.1,3 One case of first-degree heart block was deemed to be treatment related.1 One participant had a transient increase in blood pressure3 and another had slightly elevated liver enzymes.1 No potential Hy’s law cases were observed.1,3

Gepants are extensively metabolized in the liver by cytochrome P450 3A4 (CYP3A4). Typically, when 2 drugs are metabolized in the same pathway, it is expected to impact their drug levels. When atogepant and ubrogepant were taken every 3 days for 4 weeks, no clinically relevant pharmacokinetic changes or unexpected side effects were noted.4

1. Berman G, et al. Headache. 2020;60(8):1734-42;
2. Mullin K, et al. Neurology. 2020;94(20): e2121-5;
3. Jakate A, et al. Headache. 2021;61(4):642-52;
4. Blumenfeld AM, et al. Headache. 2023;63(3):322-32.