Effectiveness and Safety of Anti-CGRP Monoclonal Antibodies for Migraine Prevention in Real-World Practice: A Systematic Review

The transition from Phase III trials to real-world evidence (RWE) is critical for understanding monoclonal antibody (mAb) performance in complex, comorbid populations. This review evaluates the real-world effectiveness and safety of calcitonin gene-related peptide (CGRP) pathway inhibitors in routine clinical practice. A systematic search of PubMed (2021–2026) identified observational studies, including prospective registries (e.g., PEARL, GARLIT, MAB-MIG) and large-scale claims analyses, regarding erenumab, fremanezumab, galcanezumab, and eptinezumab. Synthesis of 32 studies (n > 1 million patients) demonstrates robust effectiveness across diverse populations. Real-world data confirm sustained ≥ 50% responder rates (ranging from 40%–75% in most cohorts) and significant reductions in acute medication use. Benefits were maintained over 12–36 months, even in patients with chronic migraine and medication overuse headaches. Large-scale analyses (MarketScan, Medicare) indicate that CGRP inhibitors are not associated with an increased risk of myocardial infarction or stroke compared to onabotulinumtoxinA, even in older adults. Switching between ligand and receptor targets remains an effective strategy for initial non-responders. RWE establishes that anti-CGRP mAbs provide durable effectiveness and high adherence in difficult-to-treat populations. The data confirm a favorable cardiovascular safety profile, supporting their role as a cornerstone of modern migraine prevention.