Comparative Efficacy and Safety of CGRP Monoclonal Antibodies and Oral Gepants for Migraine Prevention: Evidence from Randomized Controlled Trials and Network Meta-analysis
Sharath Chandra Anne1, Shradha Kakde2, Meghnath Kakde3, Ahmed Harb4, Anas Mansour4, Rakhshanda Khan5, Meghana Chennupati6, Harshawardhan Ramteke7
1pinnamaneni siddharta medical college, 2MGM medical college and hospital, 3smt.kashibai navale medical college and general hospital, 4Faculty of Medicine, Al-Azhar University, Cairo, Egypt, 5Ayaan Institute of medical sciences, 6Mamata Academy of Medical Sciences, 7Anhui medical university
Objective:
To compare the efficacy and safety of calcitonin gene–related peptide (CGRP) monoclonal antibodies and oral gepants for migraine prevention using network meta-analysis with SUCRA-based ranking.
Background:
Targeted CGRP pathway inhibition has revolutionized migraine prevention, providing superior efficacy and safety over traditional therapies. Recent trials up to October 2025 confirm the effectiveness of injectable CGRP monoclonal antibodies and the oral gepant atogepant as first-line preventive options.
Design/Methods:
A systematic search was conducted across major databases, and data were analyzed using a random-effects network meta-analysis with SUCRA ranking; risk of bias was assessed using RoB 2.0.
Results:
A total of 26 randomized controlled trials involving 17,620 participants were analyzed, including 9,213 receiving active CGRP-targeted therapy and 8,407 receiving placebo. Treatments included erenumab (n = 3,276), fremanezumab (n = 2,481), galcanezumab (n = 2,348), eptinezumab (n = 1,912), and atogepant (n = 1,196). The pooled mean reduction in monthly migraine days was −3.41 (95% CI −4.12 to −2.70; p < 0.001), and the odds ratio for achieving a ≥50% response was 2.41 (95% CI 1.98–2.93; p < 0.001). SUCRA rankings for efficacy were eptinezumab 93%, galcanezumab 88%, fremanezumab 82%, erenumab 79%, and atogepant 75%, while atogepant (89%) and eptinezumab (86%) ranked best for tolerability. The pooled risk ratio (RR) for adverse events was 1.08 (95% CI 0.96–1.21), with constipation (RR 1.64; 95% CI 1.30–2.07), injection-site reactions (RR 1.28; 95% CI 1.03–1.57), nausea (RR 1.22; 95% CI 0.97–1.54), and serious adverse events (RR 0.94; 95% CI 0.72–1.23) showing no significant safety concerns. Risk-of-bias assessment using RoB 2.0 rated 85% of trials as low risk, confirming consistent efficacy and excellent tolerability of CGRP monoclonal antibodies and oral gepants across migraine populations
Conclusions:
CGRP monoclonal antibodies and oral gepants demonstrated consistent, durable efficacy and excellent safety for migraine prevention, with overall low risk of bias across included trials.
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