Efficacy and safety of CGRP monoclonal antibodies in chronic migraine: a systematic review integrating randomized and real-world evidence

BACKGROUND AND OBJECTIVES: Chronic migraine (CM) is a highly disabling neurological disorder characterized by ≥ 15 headache days per month, of which at least 8 exhibit migrainous features. Despite the availability of preventive therapies, conventional treatments are often limited by suboptimal efficacy and poor tolerability. Monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor have emerged as mechanism-based preventive options. This systematic review aims to evaluate the efficacy, safety, and clinical relevance of CGRP-targeted monoclonal antibodies in the prevention of chronic migraine. MATERIALS AND METHODS: A comprehensive literature search of PubMed, Scopus, and Web of Science was conducted from database inception to July 2025. Randomized controlled trials and observational real-world studies evaluating CGRP-targeted monoclonal antibodies in adult patients with chronic migraine were included. The review followed PRISMA 2020 guidelines (Page et al. 2021), was registered in the PROSPERO database (CRD420261284751), and included 11 studies out of 1,688 identified records. RESULTS: Across included studies, CGRP-targeted monoclonal antibodies consistently demonstrated reductions in migraine frequency, improvements in ≥ 50% responder rates, and favorable safety profiles. Randomized controlled trials showed robust efficacy compared with placebo, while real-world studies confirmed effectiveness in more heterogeneous and treatment-resistant populations. However, variability in outcome definitions, particularly between monthly migraine days and monthly headache days, and differences in study design contributed to heterogeneity across findings. CONCLUSIONS: CGRP-targeted monoclonal antibodies represent an effective and well-tolerated preventive option for chronic migraine, with clinically meaningful benefits across both controlled and real-world settings. While current evidence is strong, further research is needed to evaluate long-term outcomes, optimize treatment strategies, and improve standardization of outcome measures. TRIAL REGISTRATION: This systematic review was registered in the PROSPERO database (CRD420261284751).