All four CGRP monoclonal antibodies significantly reduce monthly migraine days, with fremanezumab and galcanezumab showing the largest reductions, but only galcanezumab had a higher rate of adverse events than placebo.
Fremanezumab: -2.19 migraine days/monthAmong the four CGRP antibodies, fremanezumab showed the largest reduction in monthly migraine days, followed closely by galcanezumab at -2.10 days, compared to placebo.
What the researchers found
All four CGRP monoclonal antibodies significantly reduced monthly migraine days (MMDs) compared to placebo: eptinezumab (MD -1.43 days), erenumab (MD -1.61 days), fremanezumab (MD -2.19 days), and galcanezumab (MD -2.10 days).
Regarding safety, only galcanezumab showed significantly increased treatment-emergent adverse events (RR 1.11, 95% CrI 1.01–1.22) and serious adverse events (RR 2.95, 95% CrI 1.41–6.87) compared to placebo. The other three antibodies had adverse event rates comparable to placebo. Overall, the drugs performed similarly to each other across most analyses.
Why it matters
With four CGRP antibodies available, clinicians and patients need to know which one to choose. This network meta-analysis provides the most comprehensive indirect comparison to date, revealing that while all four are effective, they differ meaningfully in safety profiles. The finding that galcanezumab alone was associated with more adverse events — including serious ones — is clinically significant information for prescribing decisions.
How the study worked
This was a systematic review and network meta-analysis of 18 randomized controlled trials (n=8,926) identified from MEDLINE, Embase, ClinicalTrials.gov, and Cochrane Library databases through October 2020. Network meta-analysis allows indirect comparison between drugs that haven't been tested head-to-head by using placebo as a common comparator. Primary outcomes were changes in monthly migraine days and treatment-emergent adverse events.
What this study cannot tell us
Network meta-analysis relies on indirect comparisons, which are less reliable than head-to-head trials. The included trials varied in design, patient populations, dosing regimens, and follow-up durations. The safety signal for galcanezumab could reflect differences in trial design or patient selection rather than true drug-specific risks. Data was limited to publications through October 2020, so more recent evidence is not captured. The analysis does not distinguish between episodic and chronic migraine subgroups in detail.
How to read the evidence
This is a systematic review and network meta-analysis of 18 randomized controlled trials — a high level of evidence. However, network meta-analysis relies on indirect comparisons, which introduces uncertainty compared to direct head-to-head trials. The methodology (systematic search, multiple databases, network analysis) is rigorous.
When this study was published
Published in 2021 with data through October 2020, this analysis captures the early clinical trial evidence for CGRP antibodies. Additional real-world data and longer-term studies have since become available but were not included.
The bigger picture
The CGRP antibody class has transformed migraine prevention since 2018. As these drugs have matured in the marketplace, the clinical question has shifted from 'do they work?' to 'which one should I prescribe?' Network meta-analyses like this one help fill the gap left by the absence of head-to-head clinical trials. The safety signal for galcanezumab, while based on indirect comparison, is an important consideration as real-world data continues to accumulate.
Questions still open
- Would direct head-to-head randomized trials confirm the safety differences between galcanezumab and the other CGRP antibodies?
- Do the efficacy rankings change when episodic and chronic migraine are analyzed separately?
- How does long-term (multi-year) safety compare across the four CGRP antibodies in real-world practice?
Common questions
Which CGRP antibody is best for migraine prevention?
Are CGRP antibodies safe for long-term use?
Read the original research
Efficacy and Safety of Monoclonal Antibody Against Calcitonin Gene-Related Peptide or Its Receptor for Migraine: A Systematic Review and Network Meta-analysis.
Frontiers in pharmacology, 12, 649143
Citation
Wang, Xing; Chen, Yuqi; Song, Jinlei; You, Chao. (2021). Efficacy and Safety of Monoclonal Antibody Against Calcitonin Gene-Related Peptide or Its Receptor for Migraine: A Systematic Review and Network Meta-analysis.. Frontiers in pharmacology, 12, 649143. https://doi.org/10.3389/fphar.2021.649143