Efficacy and effectiveness of anti-CGRP monoclonal antibodies treatment in the prevention of cluster headache attacks: A systematic review and meta-analysis.

BackgroundCluster headache (CH) is one of the most severe types of pain, yet pharmacological treatment options are limited. In the present study, we aimed to systematically evaluate the effect of treatment with monoclonal antibodies (mAbs) blocking calcitonin gene-related peptide (CGRP) in the prevention of episodic cluster headache (eCH) and chronic (cCH) cluster headache.MethodsWe searched Embase, Medline, Cochrane CENTRAL and Web of Science. Included were all clinical trials, case series and single case reports that reported the effects of anti-CGRP treatment on CH. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were used for abstracting data. Risk of bias was evaluated using the Risk of Bias 2 (RoB 2) tool for randomized trials and Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) for non-randomized studies. The collected data from all studies were summarized using descriptive statistics. Data from randomized trials were additionally reported as odds ratio (OR) with 95% confidence interval (CI) using a random-effects meta-analysis. Given the variability in study design and the diverse formats of reported outcome data, we primarily focused on the ≥ 50% responder rate reported closest to the 4-week point following drug administration, which was consistently reported in almost all studies.ResultsFrom 734 identified records, 25 articles were included, comprising a total of 1587 patients. Meta-analysis of randomized, placebo-controlled trials suggests that anti-CGRP treatment had a statistically significant positive effect in eCH (OR = 1.65, 95% CI = 1.07-2.55, p = 0.02), with galcanezumab 300 mg and eptinezumab 400 mg being more effective than placebo in achieving a ≥ 50% responder rate in eCH attacks at the 4-week mark following administration. Simultaneously, a significant mean reduction in weekly attack frequency at week 4 was observed only for galcanezumab 300 mg (p = 0.04). Despite findings from some non-randomized trials, the meta-analysis showed no statistically significant effect in cCH (OR = 1.07, 95% CI = 0.78-1.48, p = 0.68).ConclusionsOur analysis revealed a beneficial effect of anti-CGRP mAbs in eCH, while no effect was observed in cCH. Despite these positive findings, the favourable results with galcanezumab and eptinezumab in eCH should be interpreted with caution due to discrepancies in the outcome data and the challenges associated with selecting endpoints in CH trials. The discrepancy between real-world data and findings from controlled trials further highlights the need for continued discussions among experts to develop more adequate methods for conducting CH trials.Trial RegistrationPROSPERO ID: CRD420250609351.