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.
- 2026-04
- Cephalalgia : an international journal of headache 46(4)
- Malahat Khalili
- Faraidoon Haghdoost
- Amin Liaghatdar
- Kian Torabiardakani
- Fatemeh Mahdian
- Tariq Atkin-Jones
- Tal Levit
- Sara Moradi
- Ehsan Hedayati
- Farzaneh Ahmadi
- Sahar Khademioore
- Ahmad Sofi-Mahmudi
- Vivek Patil
- Fatemeh Mirzayeh Fashami
- Soheil Mehmandoost
- Rachel J Couban
- Kameshwar Prasad
- Seyed-Mohammad Fereshtehnejad
- Behnam Sadeghirad
- PubMed: 42011527
- DOI: 10.1177/03331024261441287
Study Design
- Type
- Meta-Analysis
- Sample size
- n = 7,281
- Population
- adults diagnosed with chronic or episodic migraine and a prior preventive treatment failure
- Methods
- Network meta-analysis of randomized controlled trials of prophylactic pharmacological interventions
- Funding
- Mixed (industry + independent)
BackgroundDespite 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.MethodsWe 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.ResultsWe 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.ConclusionEvidence 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 numberPROSPERO (CRD42024547860).