Comparative Efficacy and Safety of Atogepant as Prophylaxis for Chronic and Episodic Migraine in Adults: a Systematic Review with Meta-Analysis and Trial Sequential Analysis
Paweł Chochoł1, Aishwarya Koppanatham2, Enzo Von Quednow3, Aisha Rizwan Ahmed4, Natalia Arturo5, Thomas Varkey6
1University of Warmia and Mazury in Olsztyn, Poland, 2Andhra Medical College, 3Complejo Hospitalario Universitario de Albacete, 4Jinnah medical and dental college, 5universidad medical college, 6Banner University Medical Center
Objective:

To evaluate the efficacy and safety outcomes of atogepant compared to placebo as migraine  prophylaxis.

Background:

Migraine affects 15% of the global population and is a major cause of disability. Preventive treatments are vital for reducing attack frequency, severity, and disability, and improving quality of life. Recent advancements, including CGRP antagonists like atogepant, have shown significant efficacy and safety in clinical trials.

Design/Methods:

PubMed, EMBASE, and Cochrane Central databases were searched for randomized controlled trials (RCTs) comparing atogepant with placebo for migraine prevention. Efficacy and safety outcomes were analyzed using Review Manager 5.4, with standardized mean differences (SMDs) and risk ratios (RRs) calculated using random-effects models. Subgroup analyses by dose and prior oral preventative failure were performed. Trial sequential analysis assessed the robustness of the findings.


Results:

Four RCTs with 2,813 patients, including 1,354 receiving atogepant, were analyzed. Atogepant significantly reduced mean monthly migraine days (SMD -0.39, 95% CI [-0.49, -0.29]), monthly headache days (SMD -0.40, 95% CI [-0.51, -0.30]), acute medication use (SMD -0.44, 95% CI [-0.70, -0.18]), and increased the 50% responder rate (RR 1.84, 95% CI [1.40, 2.42]) compared to placebo. It also improved quality of life, particularly in role function–restrictive (SMD 0.46, 95% CI [0.27, 0.66]), daily activities (SMD -0.37, 95% CI [-0.47, -0.27]), and physical impairment (SMD -0.34, 95% CI [-0.44, -0.24]) domains, and reduced headache impact (SMD -0.46, 95% CI [-0.61, -0.32]). Subgroup analysis showed benefits in patients who failed prior oral preventatives, with no dose-dependent response. Trial sequential analysis confirmed adequate study power.


Conclusions:

This meta-analysis indicates that atogepant effectively reduces migraine frequency and acute medication use while improving quality of life. Despite reports of adverse effects like constipation and nausea, the benefits outweigh the risks. Long-term safety trials and studies on chronic migraine are needed to validate these findings.

10.1212/WNL.0000000000208366
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.