Effectiveness and Tolerability of Pharmacological Prophylaxis in Migraine Patients With Prior Preventive Treatment Failure: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials Publisher Pubmed



Khalili M ; Haghdoost F ; Liaghatdar A ; Torabiardakani K ; Mahdian F ; Atkinjones T ; Levit T ; Moradi S ; Hedayati E ; Ahmadi F ; Khademioore S ; Sofimahmudi A ; Patil V ; Fashami FM Show All Authors
Source: Cephalalgia Published:2026

Abstract

Background: Despite advances in migraine management, some patients fail to respond to preventive treatments for migraine. We aimed to assess the comparative effects of available pharmacological prophylaxis in adults with a treatment failure history. Methods: We searched Medline, Embase, Cochrane Central, PsycINFO, Web of Science, and Scopus up to July 2025. Pairs of reviewers independently screened titles, abstracts, and full-text articles to identify randomized controlled trials of prophylactic pharmacological interventions that enrolled adults diagnosed with chronic or episodic migraine and a prior preventive treatment failure. We performed a frequentist random-effects network meta-analysis and used the GRADE approach to assess the certainty of evidence. Results: We included 18 randomized trials (7281 participants). Compared to placebo, low certainty evidence suggest fremanezumab [mean difference (MD) −3.30 (95% CI: −4.11 to −2.49)], eptinezumab [MD −3.35 (95% CI: −4.38 to −2.32)], galcanezumab [MD −2.73 (95% CI: −3.43 to −2.03)], atogepant [MD −2.30 (95% CI: −3.47 to −1.13)], and erenumab [MD −2.20 (95% CI: −2.72 to −1.68)] may be among the most effective in reducing the monthly migraine headache days. Low to moderate certainty evidence suggests that, compared with placebo, galcanezumab [relative risk (RR) 1.94 (95% CI: 1.52 to 2.48)], fremanezumab [RR 3.98 (95% CI: 2.40 to 6.59)], atogepant [RR 2.80 (95% CI: 1.73 to 4.54)], erenumab [RR 2.56 (95% CI: 2.01 to 3.26)], and eptinezumab [RR 2.35 (95% CI: 1.61 to 3.42)] may increase the likelihood of achieving a 50% response rate. Conclusion: Evidence for migraine patients with prior preventive treatment failure is limited. Low- to moderate-certainty data suggest that CGRP-targeted therapies may provide some benefit and are generally tolerable, but the available evidence is driven by a few industry-sponsored trials. Additional independent, well-powered studies with longer follow-up are needed to strengthen the evidence base. Registration number: PROSPERO (CRD42024547860). © International Headache Society 2026. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).