Efficacy and Safety of Fremanezumab in the Preventive Treatment of Migraine: A Systematic Review of Randomized Clinical Trials

Abstract

Context: Migraine is a highly prevalent and disabling neurological condition, affecting approximately one billion people worldwide. It is the second most common type of primary headache. Among the existing therapeutic options, many demonstrate limited efficacy and significant side effects. Fremanezumab, a monoclonal antibody that selectively blocks CGRP, has been studied as a promising alternative for migraine prevention, as it acts directly on the pathophysiological mechanisms of the disease.

Objective: This systematic review aims to gather and analyze the results of randomized clinical trials evaluating the efficacy and safety of fremanezumab as a prophylactic strategy for migraine in adults. Methods: Searches were conducted in the PubMed, Cochrane CENTRAL, and LILACS databases, covering publications from 2015 to 2025 in English, Portuguese, or Spanish. After independent and double-blinded screening of 511 records, 3 randomized clinical trials were included.

Results: In all analyzed studies, fremanezumab demonstrated superiority over placebo, with reductions ranging from 3.7 to 4.6 headache days per month and higher response rates (≥ 50% reduction), observed in up to 41% of treated patients. The most common adverse events were injection site reactions and nasopharyngitis, which were generally mild. The included studies showed good methodological quality and demonstrated benefits of fremanezumab in both treatment-responsive and treatment-refractory patients.

Conclusion: Fremanezumab appears to be an effective and safe option for the prophylaxis of episodic and chronic migraine. Nonetheless, longer-duration studies with more diverse populations and economic evaluations are needed to support its widespread, evidence-based adoption in clinical practice.