Combination GCRP Monoclonal Antibody and Gepant Treatment Shows Safety, Efficacy

Open-label data of concomitant use of CGRP monoclonal antibodies and receptor antagonists suggest that the agents can be safely and effectively combined in the treatment of migraine.

New open-label data assessing the longitudinal treatment of matched comparative groups of individuals with migraine suggest that the calcitonin gene-related peptide (CGRP) monoclonal antibodies and receptor antagonists—known as gepants—are both safe and effective when used in combination.1

All told, the study compared patients being treated with combination CGRP monoclonal antibodies and gepants (n = 17) and those being treated with standard of care therapies, topiramate or onabotulinumtoxinA (n = 14). The majority of patients in each group (CGRP, n = 15; standard of care, n = 14) had chronic migraine. Those treated with the CGRP therapies displayed similar levels of efficacy and rates adverse events (AEs), without an increase in AEs when used in combination, compared to the standard of care therapies.

The findings imply that such a combination approach may provide enhanced benefits for each group of agents, in addition to reduced adverse events and improved efficacy compared to matched controls and standard of care therapy. The data were presented at the 2021 American Headache Society (AHS) Annual Scientific Meeting, June 3-6, by Amir Soheil Tolebeyan, MD, assistant professor of neurology, Froedtert & the Medical College of Wisconsin.

“Up until now, 4 CGRP monoclonal antibodies and 2 CGRP receptor antagonists have been approved by the US Food and Drug Administration for migraine prophylaxis and abortive therapy, respectively,” Tolebeyan et al wrote. “CGRP monoclonal antibodies have proven to be more effective and, in general, have fewer risks of adverse events than the standard of care oral medications for episode or chronic migraine. They have also proven to have efficacy similar to onabotulinumtoxinA for chronic migraine prevention.”

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The CGRP group included treatment with all 4 approved monoclonal antibodies—galcanezumab (Emgality; Eli Lilly), erenumab (Aimovig; Amgen/Novartis), fremanezumab (Ajovy; Teva), and eptinezumab (Vyepti; Lundbeck). Response rates among those in the CGRP group were as follows: galcanezumab, 34%; eptinezumab, 31%; fremanezumab, 25%; erenumab 11%.

Headache frequency reductions were defined by several groupings: no benefit, 0% to 24%, 25% to 49%, 50% to 74%, and 75% to 100%. Of the 10 patients on galcanezumab, 2 patients reported no benefit, 2 reported reductions of 50% to 74%, and 6 reported 75% to 100% reductions. Of the 5 patients on fremanezumab, 1 each reported reductions of 0% to 24%, 25% to 49%, and 75% to 100%, while the remaining 2 patients reported reductions between 50% and 74%. Of the 2 patients treated with eptinezumab, 1 each reported reductions of 0% to 24% and 75% to 100%. All 3 patients treated with erenumab reported no benefit.

In the standard of care group, headache frequency was reduced by 25% or less in 1 patient on topiramate, between 25% and 49% for 1 patient on onabotulinumtoxinA and 4 on topiramate, and between 50% and 74% for 6 patients on onabotulinumtoxinA and 2 on topiramate.

“Concerns have been suggested regarding the combined use for the potential to provide an overly broad interface with CGRP systemically and increase the risk of adverse events. So far, the safety and efficacy of the concomitant use of the CGRP [monoclonal anitbodies] and gepants have been shown in just a few studies published recently,” Tolebeyan et al continued.

In total, 14 patients reported AEs across the treatment groups. Of those taking a CGRP monoclonal antibody and a gepants, 3 patients reported nausea. Of those taking onabotulinumtoxinA, 1 reported transient ptosis, and 5 reported pain. For topiramate, 1 patient reported paresthesia, and 4 reported brain fog.

Data presented by Fred Cohen, MD, internal medicine resident physician, department of medicine, Montefiore Health System, last year at the 2020 AHS Virtual Annual Scientific Meeting suggested that patients with chronic migraine receiving treatment with onabotulinumtoxinA who require additional preventive treatment can be given CGRP monoclonal antibody medications safely and effectively.

Ultimately, in a cohort of 153 patients treated with onabotulinumtoxinA, 66 continued to have 14.3 monthly headache days despite significant reductions from baseline headache days prior to treatment with onabotulinumtoxinA (baseline, 25.3 days; reduction, 10.9 days [43%]; P <.0001). The add-on of a CGRP therapy was associated with an additional decrease of 5.6 days, equating to an additional 22.3% reduction (95% CI, 4.5—6.7; P <.0001) in monthly headache days. Of the 153-patient study population, 88 (58%) were treated with erenumab, 51 (33%) were treated with galcanezumab, and 14 (9%) were treated with fremanezumab.2

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1. Tolebeyan AS, Sivakumar D, Freitag F, Shumate D, Schloemer F. CGRP Monoclonal Antibodies Along with CGRP Receptor Antagonists Are Safe and Effective Together and Compared to Standard of Care. Presented at 2021 AHS Annual Scientific Meeting; June 3-6. Abstract P155.
2. Cohen F, Armand C, Vollbracht S. Efficacy and Tolerability of CGRP Monoclonal Antibody Medications in Patients with Chronic Migraine Undergoing Treatment with OnabotulinumtoxinA. Headache. 2020;60(S1 suppl). 1-156. doi: 10.1111/head.13854