All four CGRP-targeting monoclonal antibodies (eptinezumab, erenumab, galcanezumab, fremanezumab) showed comparable migraine prevention efficacy in phase 2 trials with excellent safety profiles, though their effectiveness was similar to existing oral medications.
NNT 4.0-6.2All four CGRP antibodies showed clinically meaningful efficacy in migraine prevention with adverse event rates essentially indistinguishable from placebo
What the researchers found
In high-frequency episodic migraine, the reduction in monthly migraine days from baseline versus placebo at end of treatment was:
- Eptinezumab (ALD403): -1.0 days (weeks 5-8)
- Erenumab (AMG334): -1.1 days (weeks 9-12)
- Galcanezumab (LY2951742): -1.2 days (weeks 9-12)
- Fremanezumab (TEV48125, 225 mg): -2.6 days (weeks 9-12)
Numbers needed to treat (NNT) for responders were 4.7, 6.2, 4.0, and 4.0 respectively — all clinically meaningful. The odds ratios for any adverse event were remarkably close to 1.0 (1.09, 0.96, 1.07, 1.05), indicating that side effects were essentially no different from placebo. The authors noted that overall efficacy was comparable to existing oral preventive migraine medications, but the safety and tolerability advantages were the key differentiator.
Why it matters
This review captured a pivotal moment in headache medicine — when the first disease-specific preventive migraine treatments were emerging. Previous preventive medications (beta-blockers, antidepressants, antiepileptics) were all repurposed from other conditions and came with significant side effects. CGRP antibodies represented the first treatments designed specifically for migraine based on understanding the underlying peptide biology, fundamentally changing how the condition is managed.
How the study worked
Comparative review of published phase 2 randomized controlled trials for all four CGRP-targeting monoclonal antibodies in episodic and chronic migraine prevention. The authors standardized comparisons across trials by examining change from baseline in migraine days, number needed to treat, and odds ratios for adverse events.
What this study cannot tell us
This review was based on phase 2 trial data only — smaller and shorter than the subsequent phase 3 trials. Cross-trial comparisons are inherently limited because the studies had different designs, patient populations, and endpoints. Long-term safety data was not available at the time. The review noted that pregnancy safety, cardiovascular effects, and cost-effectiveness required further evaluation — questions that have since been partially addressed.
How to read the evidence
This is a comparative review of phase 2 randomized controlled trials — well-designed studies but with smaller patient populations and shorter durations than the subsequent phase 3 confirmatory trials. The cross-trial comparison format limits direct head-to-head conclusions but provides useful context for the entire CGRP antibody class.
When this study was published
Published in 2017 when these drugs were still in late-stage development, this review preceded the FDA approvals of erenumab (2018), fremanezumab (2018), galcanezumab (2018), and eptinezumab (2020). The predictions about these drugs changing headache management have been confirmed.
The bigger picture
The CGRP antibody class represents one of the most successful applications of peptide biology to clinical medicine. Understanding that the neuropeptide CGRP drives migraine pathophysiology led to four approved antibody therapies and multiple small-molecule CGRP receptor antagonists (gepants). This has validated the concept that targeting specific neuropeptide pathways can treat neurological conditions, inspiring similar approaches for other pain conditions and neurological disorders.
Questions still open
- Do any of the four CGRP antibodies have clinically meaningful advantages over the others in specific patient populations?
- What are the long-term cardiovascular safety implications of blocking CGRP, which has known vasodilatory functions?
- How do CGRP antibodies compare to the newer oral CGRP receptor antagonists (gepants) for patients who prefer non-injectable options?
Common questions
What are CGRP antibodies and how do they prevent migraines?
Which CGRP antibody is best for migraine prevention?
Read the original research
Calcitonin gene-related peptide monoclonal antibodies for migraine prevention: comparisons across randomized controlled studies.
Current opinion in neurology, 30(3), 272-280
Citation
Mitsikostas, Dimos D; Reuter, Uwe. (2017). Calcitonin gene-related peptide monoclonal antibodies for migraine prevention: comparisons across randomized controlled studies.. Current opinion in neurology, 30(3), 272-280. https://doi.org/10.1097/WCO.0000000000000438