Persistence and Reasons for Treatment Discontinuation of Anti-CGRP Therapies in Migraine Prophylaxis: A Systematic Review and Meta-analysis of Real-World Studies.

INTRODUCTION

Anti-calcitonin gene-related peptide (anti-CGRP) therapies have become a mainstay of migraine prophylaxis. In routine care, treatment persistence and the reasons patients discontinue are indicators of long-term effectiveness, tolerability, and acceptability, but the available real-world evidence is fragmented across settings. We aimed to synthesize treatment persistence at 3, 6, and 12 months and to summarize the documented reasons for discontinuation.

METHODS

This systematic review and meta-analysis (PROSPERO CRD420261298053) searched Embase (via Ovid) and PubMed for real-world studies with a clinical follow-up of adults receiving an anti-CGRP therapy for migraine prophylaxis with longitudinal follow-up. Persistence, defined as the proportion of patients remaining on treatment from initiation, was pooled using random-effects meta-analysis of proportions. Reasons for discontinuation were pooled descriptively. Exploratory subgroup analyses examined migraine type, drug class, and individual monoclonal antibody.

RESULTS

Fifty-three studies were included. Pooled persistence was 93.3% (95% CI 90.2-95.9) at 3 months, 84.2% (80.4-87.6) at 6 months and 76.2% (69.7-82.2) at 12 months, with substantial heterogeneity throughout (I2 82-93%). Among 1242 documented discontinuation events, lack of efficacy was the leading reason (63.7%), followed by adverse events or poor tolerability (15.1%). Persistence did not differ significantly by migraine type or between individual monoclonal antibodies. Atogepant showed lower 3-month persistence than monoclonal antibodies (83.5% vs. 94.2%; p = 0.013), although data were limited to early follow-up.

CONCLUSIONS

Approximately three-quarters of patients remain on anti-CGRP therapy at 1 year, with most discontinuation occurring within the first six months and driven mainly by perceived lack of efficacy rather than tolerability. Marked between-study heterogeneity warrants cautious interpretation and more standardized reporting of persistence in future real-world studies.