Anti-CGRP migraine drugs mildly increase infection risk with NNH of 287, mainly galcanezumab and eptinezumab | Research

The takeaway

Meta-analysis of 37 RCTs (22,518 patients) shows CGRP-targeting preventive therapies mildly increase infection risk (RR 1.08, NNH 287), with galcanezumab (NNH 77) and eptinezumab (NNH 24) driving the signal while fremanezumab shows fewest infectious SAEs.

NNH = 287 for infections
CGRP-blocking migraine drugs mildly increase infection risk—287 patients treated for one additional infection—clinically manageable but important for immunocompromised patients

What the researchers found

Overall: RR 1.08 (1.01-1.14, p=0.016), NNH=287. Galcanezumab: RR 1.13 (p=0.024), NNH=77. Eptinezumab higher doses: RR 1.23 (p=0.015), NNH=24. Fremanezumab: fewest SAEs. Erenumab: most SAEs. 37 RCTs, 22,518 patients.

Why it matters

CGRP plays a role in immune defense. This is the first comprehensive analysis confirming a small but real infection risk increase with CGRP-blocking therapies—important for immunocompromised patients or public health contexts.

How the study worked

Systematic review per PRISMA-Harms. 37 placebo-controlled RCTs. Fixed/random effects NMA. Risk of bias and sensitivity analyses. Infectious SAE search in DB and OLE studies.

What this study cannot tell us

Infection definitions varied across trials. Short trial durations may underestimate long-term risk. NNH is relatively high (287). Individual drug differences may reflect dosing rather than molecular differences.

How to read the evidence

Meta-analysis of 37 RCTs with >22K patients. High-quality evidence for a small but real safety signal.

When this study was published

Published in 2025.

The bigger picture

CGRP is not just a pain mediator—it modulates immune responses. Blocking it therapeutically carries a trade-off: migraine relief at the cost of slightly reduced infection defense. This is clinically manageable but important to acknowledge.

Questions still open

Should immunocompromised patients avoid certain CGRP therapies?
Does long-term CGRP blockade increase infection severity?
Is the infection risk specific to antibodies vs small molecule CGRP blockers?

Common questions

Do CGRP migraine drugs weaken the immune system?

Slightly. This large analysis found a small increase in infection risk (8% relative increase), meaning about 1 extra infection per 287 patients treated. This is because CGRP plays a role in immune defense. For most healthy patients, this risk is very low, but immunocompromised patients should discuss it with their doctor.

Which CGRP migraine drug is safest for infections?

Fremanezumab had the fewest infection-related serious adverse events. Galcanezumab and eptinezumab showed the highest infection risk signals. If infection risk is a concern, discussing drug choice with your neurologist is worthwhile.

Read the original research

Increased infection risk in patients on preventive CGRP-targeting therapies- a meta-analysis and clinical effect assessment.

The journal of headache and pain, 26(1), 88

View on PubMed ↗Publisher’s paper ↗

Citation

Straburzyński, Marcin; Kopyt, Daria; Marschollek, Karol; Błaszczyk, Bartłomiej; Kuca-Warnawin, Ewa; Kurowska, Weronika; Misiak, Błażej; Peng, Kuan-Po; Waliszewska-Prosół, Marta; May, Arne. (2025). Increased infection risk in patients on preventive CGRP-targeting therapies- a meta-analysis and clinical effect assessment.. The journal of headache and pain, 26(1), 88. https://doi.org/10.1186/s10194-025-02040-0