Efficacy and Safety of Fremanezumab in Episodic Migraine: A Systematic Review and Meta-analysis.

BACKGROUND: Fremanezumab, a calcitonin gene-related peptide monoclonal antibody, is approved for migraine prevention, yet evidence specific to episodic migraine remains limited. We synthesized randomized evidence on its efficacy and safety. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO CRD420261385104), we systematically searched PubMed, Embase, and Scopus from inception to June 5, 2026, for placebo-controlled randomized controlled trials (RCTs) evaluating fremanezumab for episodic migraine prevention. Primary outcomes were the ≥50% responder rate and change in monthly migraine days. Random-effects meta-analyses were performed, and risk of bias was assessed using the Cochrane RoB 2 tool. RESULTS: Four RCTs including 1764 participants were included. Fremanezumab significantly increased the ≥50% responder rate (risk ratio: 1.81, 95% CI: 1.53-2.15) and reduced monthly migraine days (mean difference: -1.98, 95% CI: -2.93 to -1.03), headache days, acute medication-use days, and migraine-related disability. Overall safety was comparable to placebo, with no significant differences in treatment-emergent adverse events, serious adverse events, or treatment discontinuations; injection-site induration occurred more frequently with fremanezumab. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This meta-analysis strengthens the evidence supporting fremanezumab as an effective and generally well-tolerated preventive therapy for episodic migraine. The demonstrated reductions in migraine frequency, disability, and acute medication use, together with flexible monthly and quarterly dosing, support its use in appropriately selected patients and may facilitate individualized treatment decisions by clinicians and pharmacists. Although the inclusion of pediatric data expands the current evidence base, these findings should be interpreted cautiously because they are derived from a single randomized trial. CONCLUSION: Fremanezumab is an effective and generally well-tolerated preventive treatment for episodic migraine. Evidence is robust in adults, whereas pediatric findings remain preliminary and warrant confirmation in future randomized trials.