Safety and Efficacy of Atogepant for Migraine Prevention: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Migraine represents a widespread neurological disorder that causes substantial disability and impacts on quality of life and functioning. An oral calcitonin gene-related peptide (CGRP) receptor antagonist, atogepant, is a new targeted preventive treatment for migraine. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety profile of atogepant in migraine prevention. According to the PRISMA guidelines, relevant studies were identified through a thorough database search in the PubMed, Cochrane, and ScienceDirect databases to identify all randomized controlled trials (RCTs) evaluating atogepant in adults with episodic or chronic migraine. A total of six high-quality RCTs and 3,453 patients were included. The outcomes evaluated were monthly migraine days (MMDs), monthly headache days (MHDs), acute migraine medication use, and adverse events. Pooled analysis demonstrated that atogepant significantly reduced MMDs (mean difference (MD) = -1.47; 95% CI -1.73 to -1.21), MHDs (MD = -1.71; 95% CI -1.95 to -1.48), and acute migraine medication use (MD = -1.69; 95% CI -1.94 to -1.44) compared with placebo across dose levels. Higher doses with reductions were observed, particularly with the 60 mg once-daily and 30 mg twice-daily doses. Atogepant was effective in hard-to-treat populations such as those with chronic migraine and headaches related to medication overuse. The overall risk of adverse events was slightly higher with atogepant than with placebo (RR = 1.13; 95% CI 1.01 to 1.25), although most events were mild to moderate, including nausea, constipation, fatigue, and decreased appetite. Findings from the subgroup analyses indicated that the 30 mg twice-daily regimen may be linked to an increased risk of adverse events, suggesting differences in tolerability between doses. In general, atogepant was well tolerated and safe, demonstrating good safety and tolerability relative to other traditional preventive migraine medications. This study provides evidence supporting the effectiveness and tolerability of atogepant as an oral preventive treatment for episodic and chronic migraine.