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

Pellesi L, Yangjeh A, Hajjaj I, Onan D, Waliszewska-Prosół M, Martelletti P

Pain and therapy, 2026

Abstract

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…

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