Abstract text (incl. figure legends and references)

Objective: We aimed to critically review the role of CGRP-mAbs (monoclonal antibodies against the calcitonin gene-related peptide or receptor) namely erenumab, galcanezumab, fremanezumab and eptinezumab for chronic migraine (CM) prevention.

Methods: We searched PUBMED for all CGRP-mAbs trials conducted for CM prevention in adults. We analyzed the pivotal double-blind (DB) placebo-controlled trials of at least 12 weeks duration for efficacy and safety, post-hoc studies for subgroup analysis, patient-reported outcomes (PRO) for meaningful differences, and long-term trials for safety and effectiveness.

Results: We analyzed a total of 61 studies. The results are summarized in table1. In the DB trials, the difference in reduction of migraine headaches days between CGRP-mAbs and placebo ranged from 1.7 to 2.6 days. ≥50% responder rate varied from 27.6% to 61.4%. The best results for both these outcomes were obtained by 300mg quarterly (12 weekly) intravenous eptinezumab. The difference in reduction of acute medication days between CGRP-mAbs and placebo ranged from 1.2 to 2.6 (the best result was obtained by monthly subcutaneous140mg erenumab). Mild, self-limiting adverse effects were reported. Post-hoc analyses showed that these drugs were effective in patients with coexistent medication overuse and prior failure to multiple preventives. PRO such as disability, functionality, and quality of life also showed significant and meaningful improvements. Long-term trials (1to 5years) showed consistent efficacy, no significant immunogenicity and no new safety concerns. References: Figure 1 and 2.

Conclusion: Erenumab, galcanezumab, fremanezumab and eptinezumab showed statistically superior and clinically meaningful efficacy compared with placebo for the prevention of CM with good long-term tolerability and safety profile.