Galcanezumab 120mg/1ml solution for injection pre-filled disposable devices

This study aimed to summarize and pool real‐world evidence on the clinical effectiveness and safety of galcanezumab.

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Migraine is a leading cause of global disability, and conventional preventive therapies often suffer from poor tolerability and low adherence. Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs: erenumab, fremanezumab, galcanezumab, and eptinezumab) represent a targeted therapeutic advance, but long-term adherence and safety remain under investigation. Following PRISMA guidelines, we systematically searched PubMed, Embase, CENTRAL, Scopus, and Web of Science (2018-2024) for randomized controlled trials, real-world studies, and systematic reviews reporting adherence, tolerability, or discontinuation outcomes in adults with episodic or chronic migraine. Eleven studies (n > 50,000) met the inclusion criteria. Pooled 12-month adherence was approximately 55% (vs. ~35% for oral preventives), while discontinuation due to adverse events ranged from 5.9%-20%, most commonly constipation and injection-site reactions (relative risk, 1.32-1.55); serious adverse events were rare (<5%). Responder rates (≥50% reduction in monthly migraine days) improved from 44% at three months to 64% at 12 months, with network meta-analyses suggesting greater efficacy compared with topiramate and OnabotulinumtoxinA, though direct head-to-head RCTs remain lacking. Overall, anti-CGRP mAbs demonstrate favorable adherence, sustained tolerability, and comparative advantages over conventional therapies, but further research is needed to assess long-term safety beyond 12 months, cost-effectiveness, and use in special populations such as pregnancy.

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BackgroundVestibular migraine causes recurrent vertigo attacks that significantly impact quality of life. While various preventive medications are used, their comparative effectiveness was unknown. Previous systematic reviews have been limited by pairwise comparisons only or exclusion of newer treatments. The lack of head-to-head trials comparing all available treatments further complicates evidence-based decision-making. This evidence gap has real-world consequences, has also substantial economic burden of Vestibular migraine. There is a need for direct comparison studies between the most promising treatments to provide clearer guidance for clinical practice.ObjectiveTo determine the comparative effectiveness and safety of preventive treatments for vestibular migraine through systematic review and network meta-analysis. Given the lack of head-to-head randomized trials, a network meta-analysis (NMA) provides the most appropriate method to compare available treatments by combining both direct and indirect evidence.MethodsWe searched Embase, Scopus, PubMed, and Cochrane Library from inception to January 15, 2025. We included randomized controlled trials (RCTs) and prospective observational studies (n ≥ 30 for CGRP antagonists) comparing preventive treatments for vestibular migraine diagnosed according to either Bárány Society/International Headache Society criteria (post-2012) or Neuhauser criteria (pre-2012). Primary outcomes were monthly vertigo frequency and quality of life (DHI scores). We conducted frequentist network meta-analysis and assessed certainty using GRADE.ResultsFrom 340 identified records, nine studies met inclusion criteria. Five RCTs (419 patients) comparing seven treatments were included in the network meta-analysis. All treatments significantly reduced monthly vertigo attacks versus control. Propranolol ranked highest (P-score: 0.794; -7.04 attacks/month, 95% CI -12.77 to -1.31), followed by valproic acid (-5.95, 95% CI -9.01 to -2.89) and venlafaxine (-5.94, 95% CI -8.98 to -2.90). Galcanezumab showed moderate efficacy (-5.80, 95% CI -10.61 to -0.99) with zero discontinuations. Network heterogeneity was negligible (τ²ConclusionsAll evaluated treatments effectively reduce vertigo frequency in vestibular migraine. While propranolol showed the largest effect, this relied on indirect evidence. Galcanezumab offers the best balance of efficacy, tolerability, and evidence quality. Head-to-head trials are urgently needed.Prospero registrationCRD420251089507.

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Botulinum toxin type A (BoNT-A) is an established preventive therapy for chronic migraines; however, uncertainty remains regarding its comparative efficacy and safety. Thus, we aimed to summarize current evidence from high-quality systematic reviews of the therapeutic effects of BoNT-A in migraine management. An umbrella review was conducted following PRISMA guidelines and registered in PROSPERO. High-quality systematic reviews with meta-analysis evaluating BoNT-A efficacy were identified through five databases up to August 2024. Primary outcomes included monthly headache frequency and severity. Methodological quality and risk of bias were assessed using the umbrella review checklist. Fourteen articles were included. Overall, quantitative evidence indicated favorable effects of BoNT-A compared with placebo for chronic migraines, across headache frequency, headache severity, and acute medication use, but less efficacy than topiramate and the CGRP monoclonal antibodies (CGRPmAbs) galcanezumab and fremanezumab. Though the adverse events were frequent, BoNT-A was generally well-tolerated. Comparative data suggested superior tolerability versus topiramate and a safety profile like CGRPmAbs. Although botulinum toxin type A is widely used as a preventive treatment for chronic migraines, the available evidence supports its efficacy at a moderate level. Further head-to-head and long-term analyses are needed to clarify its comparative role alongside newer biologic treatments.

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ObjectiveCalcitonin gene-related peptide (CGRP) inhibitors, including monoclonal antibodies (mAbs) and small-molecule antagonists (gepants), have transformed migraine treatment. Although clinical trials established their efficacy and initial safety, post-marketing surveillance is essential for understanding their real-world safety profile in a broader population. Therefore, this study aims to systematically review and synthesize findings from published pharmacovigilance studies that analyze potential safety signals for CGRP inhibitors using major international databases, including the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), the World Health Organization's (WHO's) VigiBase, and EudraVigilance, in order to establish a comprehensive real-world safety profile to guide clinical practice.MethodsA systematic search was conducted in major electronic databases for studies published up to September 2025. Study selection, data extraction, and quality assessment were performed by two independent researchers. We included original research articles analyzing FAERS, VigiBase, or EudraVigilance for AEs associated with erenumab, galcanezumab, fremanezumab, eptinezumab, rimegepant, ubrogepant, atogepant, or zavegepant. Data on key signals of disproportionate reporting (SDRs) and quantitative measures of disproportionality were extracted and synthesized thematically.ResultsThe search identified 30 eligible studies. For mAbs, consistent SDRs included injection site reactions, alopecia (e.g., fremanezumab reporting odds ratio (ROR) ranging from 2.73 to 6.9), constipation (primarily for erenumab, RORs ranging from 4.92 to 17.94), and a range of cardiovascular events. For gepants, common SDRs included nausea and fatigue or somnolence, with highly specific SDRs for severe constipation for atogepant (ROR025 = 19.99) and dysgeusia for zavegepant (ROR025 = 212.07), linked to its nasal administration. A critical divergence was observed for rare but serious cerebrovascular events: SDRs for reversible cerebral vasoconstriction syndrome (RCVS [erenumab ROR 9.43, 95% confidence interval {CI} 4.5-19.8]) and cervical artery dissection (CeAD [galcanezumab ROR 14.0, 95% CI 6.22-31.4]) were associated with certain mAbs. Conversely, no such SDRs have been detected for gepants to date, although this distinction requires confirmation as real-world exposure increases. However, a class-level SDR for cerebrovascular diseases as a whole was identified for CGRP inhibitors as a group (ROR 1.22, 95% CI 1.12-1.33). Also notable were shared SDRs for Raynaud's phenomenon and alopecia across both subclasses. Finally, concerning safety in pregnancy, the data are complex: while comprehensive class-level analyses did not identify a disproportionality signal compared to triptans, some analyses of individual drugs have identified reporting patterns that warrant cautious interpretation, underscoring the need for further dedicated pharmacovigilance studies to fully clarify the safety profile in this population.ConclusionsThis systematic review confirms that CGRP inhibitors have a manageable yet complex safety profile. It distinguishes rare, serious cerebrovascular events (RCVS, CeAD) associated with some mAbs but not with gepants, as well as shared adverse effects such as Raynaud's phenomenon and alopecia. Significant heterogeneity in safety profiles-from erenumab's pronounced constipation SDR to zavegepant's unique dysgeusia-challenges the view of CGRP inhibitors as a monolithic category. These findings provide a clear rationale for personalized risk assessment, enabling clinicians to tailor treatment to individual patient profiles.

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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.

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