Bridging CGRP mAbs with Gepants: An innovative approach to address the wearing-off phenomenon.

Abstract

Introduction: The introduction of calcitonin gene-related peptide (CGRP)-targeted therapies, including monoclonal antibodies (mAbs) and gepants, has revolutionized migraine management by reducing attack frequency, severity, and duration. However, concerns have emerged regarding the potential wearing off effect, where treatment efficacy diminishes before the next scheduled dose. This study evaluates the long-term efficacy and safety of bridging CGRP mAbs with gepants across 16 clinic visits over 24 months of follow-up, to manage the wearing-off phenomenon of mAbs.

Methods: This was a retrospective, real-world, exploratory study. The participants included in the study were adult (≥ 18 years) patients diagnosed with migraine. Screening for patients who had received CGRP mAbs for a minimum of 12 months was done. Clinical data was collected from electronic medical records. A total of 439 patients with documented follow-up visits while taking CGRP mAbs were identified. Data was collected from one site, the American Center for Psychiatry and Neurology, Abu Dhabi, UAE.

Results: Out of the 493 patients, 65 patients had a wear-off effect of CGRP mAbs and were on bridging treatment. Eptinezumab (55.38 %) was the most prescribed CGRP mAb, followed by erenumab (26.15 %) and galcanezumab (18.46 %). Rimegepant (95.38 %) was the primary gepant used for bridging therapy. Weekly headache days (WHD) decreased significantly over the 16 visits, from 4 days at baseline to near zero by visit 16. 41.54 % of patients improved in severity, while 46.15 % remained stable.

Conclusion: These findings strongly suggest the effectiveness of gepants in managing the wearing-off phenomenon across patients on mAbs. They also underscore the importance of individualized treatment approaches. While CGRP-targeted treatments remain highly effective, ongoing research is essential to optimize long-term use and minimize fluctuations in efficacy, ultimately improving patient reported outcomes.