Galcanezumab Efficacy and Safety Confirmed in Meta-Analysis of Real-World Studies

A meta-analysis of 36 real-world studies involving 3,859 participants demonstrated that galcanezumab (Emgality; Eli Lilly) substantially reduced monthly migraine and headache days while maintaining a favorable safety profile in a cohort of individuals wtih chronic or episodic migraine.1

Within the first month of treatment, participants experienced mean reductions of 6.93 monthly migraine days (MMD) and 8.55 monthly headache days (MHD), with effects progressively improving through 12 months of treatment. Within the first 3 months, more than 60% of participants achieved at least a 50% reduction in monthly migraine or headache days, according to the findings published in the journal Headache.1

Migraine affects more than 1 billion people worldwide and represents a leading cause of disability, particularly among young women, senior author Ivan Cavero-Redondo, PhD, of the Faculty of Nursing at University of Castilla-La Mancha, and colleagues wrote. While randomized controlled trials have established galcanezumab's efficacy and shown treatment-related adverse events rates to be low, real-world outcomes can differ from controlled study conditions.

Diverse International Study Population

The systematic search of databases comprised PubMed, Scopus, and Web of Science from inception through February 2025. The final analysis included 19 prospective, 16 retrospective, and one cross-sectional study. Investigations were conducted primarily in European countries (particularly Italy and Spain), with additional studies from Asia, Brazil, Australia, and the United States.

"Our analysis included a wide range of adult patients, that is, young and older, male and female, with and without medication overuse, with and without multiple previous treatment failures...responders and nonresponders, patients with episodic migraine and chronic migraine, and patients previously treated with CGRP monoclonal antibodies," Cavero-Redondo et al wrote.

The mean age of the participants ranged from 35.5 to 69.8 years, 80.17% had chronic migraine, 81.4% were women, and 60.9% had a history of medication overuse.

Improvement Across Outcome Measures

The treatment effects showed progressive improvement across multiple outcome measures. For MMD, mean reductions ranged from 6.93 days at 1 month to 10.90 days at 12 months, while MHD decreased from 8.55 days at 1 month to 10.97 days at 12 months, according to the study.

Participants also experienced substantial improvements in functional measures, with Headache Impact Test-6 scores declining 7.96 to 11.97 points across the 12-month period. Migraine Disability Assessment Scale (MIDAS) scores showed reductions of 42.61 points at 3 months and 50.52 to 55.17 points from 6 to 12 months.

Days requiring acute migraine medication decreased 6.79 to 13.01 days, while acute medication intake fell 11.85 to 19.35 units across the treatment period. Pain intensity scores declined 1.67 to 2.29 points from 3 to 12 months.

Researchers also reported clinically meaninful benefits across response rates. At 3 months, 63% of participants achieved at least a 50% reduction in monthly migraine days, with similar proportions maintained through 6 months. Approximately one-third of participants achieved at least a 75% response rate, while 3% to 7% experienced complete response.

Adverse events occurred in 23% of participants at 3 months, 25% at 6 months, and 35% at 12 months, with constipation the most common (6% at 3 months and 16% at 6 months. Cavero-Redondo and colleagues characterized overall adverse event profiel as low and mild.

Factors Associated with Treatment Response

Results of metaregression analyses revealed that treatment response was associated with several different factors. The researchers reported that higher baseline outcome values were associated with greater absolute reductions in MMD, MIDAS scores, medication days, and acute medication intake. Conversely, medication overuse showed negative associations with improvements in MIDAS score at 9 and 12 months, they wrote.

Female sex was associated with smaller treatment effects for MMD across all time points and for MHD at 3 months. Of note, Cavero-Redondo et al found that European studies demonstrated slightly greater reductions in several outcomes compared with non-European populations.

Among the study's limitations the authors acknowledge the absence of control groups in the majority of studies included in the meta-analysis. They also noted considerable heterogeneity across outcomes, potential publication bias for some measures, and geographic concentration in Spain and Italy for European studies. They also suggested that better results at later time points may partly reflect treatment discontinuation by nonresponders.1

Authors' Commentary

The high heterogeneity observed across studies, the authors cautioned, limits the certainty of evidence, underscoring the need for additional high-quality, controlled comparative research to confirm galcanezumab's effectiveness and safety profile. Future studies examining demographic, genetic, and treatment-change factors are needed to identify optimal treatment strategies and determine which participant subgroups may derive the greatest benefit from this therapy.1

Cavero-Redondo and colleagues concluded, however: "Galcanezumab may play a key role in the management of migraine in clinical practice, providing effective and well-tolerated treatment. Importantly, it offers a therapeutic option for patients with multiple comorbidities or a high baseline disease burden, improving quality of life by alleviating migraine and reducing the need for acute medication."1

Galcanezumab, approved by the FDA in 2018 for migraine prevention, is the only CGRP monoclonal antibody that has demonstrated 50%, 75%, and 100% responder rates in adults with episodic migraine during the first 1 to 6 months of treatment. The FDA approved expansion of the original indication in June 2019 to include the treatment of episodic cluster headache.2

References

1. Fernández-Bravo-Rodrigo J, Pascual-Morena C, Saz-Lara A, et al. Real-world effectiveness and safety of galcanezumab for the treatment of migraine: A systematic review and meta-analysis. Headache. Published online November 17, 2025. doi:10.1111/head.70003
2. FDA approves first treatment for episodic cluster headache that reduces the frequency of attacks. News release. FDA. June 4, 2019. Accessed November 25, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-episodic-cluster-headache-reduces-frequency-attacks