CGRP monoclonal antibodies effectively reduce chronic migraine frequency and improve responder rates across diverse patient populations.

Chronic migraine (CM), defined by ≥15 headache days monthly with ≥8 migrainous features, is a severely disabling neurological disorder. Current preventive therapies often fall short due to suboptimal efficacy and poor tolerability, leaving a significant treatment gap. Monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor have emerged as a mechanism-based approach to address this, offering a novel pathway for prevention. This review synthesizes evidence on their efficacy and safety.

This systematic review integrated evidence from 11 studies (out of 1,688 identified records) evaluating CGRP-targeted monoclonal antibodies in adult patients with chronic migraine. Researchers conducted a comprehensive literature search across PubMed, Scopus, and Web of Science from inception until July 2025. The review included both randomized controlled trials (RCTs) and observational real-world studies, adhering to PRISMA 2020 guidelines and registered in PROSPERO (CRD420261284751). The primary endpoints assessed were reductions in migraine frequency, ≥50% responder rates, and safety profiles.

CGRP-targeted monoclonal antibodies consistently demonstrated significant reductions in migraine frequency and improved ≥50% responder rates across all included studies.

Randomized controlled trials showed robust efficacy of CGRP mAbs compared with placebo, confirming their effectiveness in controlled settings. Real-world studies further corroborated these findings, extending the observed benefits to more heterogeneous and treatment-resistant patient populations, highlighting broad applicability. The safety profiles were consistently favorable across both study types, indicating good tolerability. However, the review noted variability in outcome definitions, particularly between monthly migraine days and monthly headache days, and differences in study design, which contributed to heterogeneity in the overall findings.