Patient Adherence and Long-Term Tolerability of Anti-calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibodies in Migraine Prevention: A Systematic Review

Migraine is a leading cause of global disability, and conventional preventive therapies often suffer from poor tolerability and low adherence. Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs: erenumab, fremanezumab, galcanezumab, and eptinezumab) represent a targeted therapeutic advance, but long-term adherence and safety remain under investigation. Following PRISMA guidelines, we systematically searched PubMed, Embase, CENTRAL, Scopus, and Web of Science (2018-2024) for randomized controlled trials, real-world studies, and systematic reviews reporting adherence, tolerability, or discontinuation outcomes in adults with episodic or chronic migraine. Eleven studies (n > 50,000) met the inclusion criteria. Pooled 12-month adherence was approximately 55% (vs. ~35% for oral preventives), while discontinuation due to adverse events ranged from 5.9%-20%, most commonly constipation and injection-site reactions (relative risk, 1.32-1.55); serious adverse events were rare (<5%). Responder rates (≥50% reduction in monthly migraine days) improved from 44% at three months to 64% at 12 months, with network meta-analyses suggesting greater efficacy compared with topiramate and OnabotulinumtoxinA, though direct head-to-head RCTs remain lacking. Overall, anti-CGRP mAbs demonstrate favorable adherence, sustained tolerability, and comparative advantages over conventional therapies, but further research is needed to assess long-term safety beyond 12 months, cost-effectiveness, and use in special populations such as pregnancy.