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Updated: May 10, 2025
Detection and Quantification of Calcitonin Gene-Related Peptide CGRP in Human Plasma Using a Modified Enzyme-Linked Immunosorbent Assay
Published on: June 16, 2023
Increased infection risk in patients on preventive CGRP-targeting therapies- a meta-analysis and clinical effect
Marcin Straburzyński1, Daria Kopyt2, Karol Marschollek3
1Department of Family Medicine and Infectious Diseases, University of Warmia and Mazury in Olsztyn, Warszawska 30, Olsztyn, 10-082, Poland. marcin.straburzynski@uwm.edu.pl.
Background:
Calcitonin gene related peptide (CGRP) pathway targeting therapies have proven efficacy, safety and tolerability. However, CGRP is also involved in immune responses, and reports of an increased risk of infection have emerged. This meta-analysis aims to verify whether CGRP-targeting therapies show evidence of increasing infection risk.
Methods:
A systematic review was conducted according to PRISMA-Harms guidelines. A PubMed and Embase search result selection and extraction was performed. Risk of bias, sensitivity analysis, and fixed/random effects network meta-analyses were conducted for incidence of infectious adverse events in the studied populations with subsequent effect size assessment. An additional infectious serious adverse event search was performed in double-blind and open-label studies.
Results:
The search and selection process yielded 37 randomized placebo-controlled trials. 22,518 patients (77.3% women) treated with erenumab, fremanezumab, galcanezumab, eptinezumab, atogepant and rimegepant participated in these studies. Preventive CGRP-targeting therapies appear to increase the infection relative risk (RR = 1.08 [1.01; 1.14], p = 0.016, Number Needed to Harm [NNH] = 287). However, in individual analyses only galcanezumab and eptinezumab showed an increase in risk of infections: galcanezumab at clinically used doses (RR 1.13 [1.02; 1.25], p = 0.024, NNH = 77); eptinezumab at higher doses (RR 1.23 [1.04; 1.45], p = 0.015, NNH = 24). Fremanezumab was associated with fewest infectious SAEs (n = 3 in 3 studies), while erenumab showed the highest incidence of these events (n = 36 in 11 studies).
Conclusions:
CGRP has multiple and often potentially opposing effects on the immune system. In effect, preventive CGRP pathway antagonists (especially eptinezumab and galcanezumab) possibly only mildly increase the risk of infections. However, it is unlikely to affect most migraine patients considering relatively high NNH, low effect size and few infectious SAEs reported so far. The result of CGRP-targeting therapies potentially depends on the type of pathogen and patient's immune status. Consequently, in immunocompromised patients or at public health levels the increased infection risk may have more pronounced effect.
Insights
Calcitonin gene-related peptide (CGRP) pathway therapies may slightly increase infection risk, particularly eptinezumab and galcanezumab. However, the overall risk for most migraine patients remains low due to a high number needed to harm.
Area of Science:
- Immunology and Neurology
- Pharmacology of CGRP pathway inhibitors
Background:
- Calcitonin gene-related peptide (CGRP) pathway targeting therapies demonstrate efficacy and safety in clinical use.
- Emerging reports suggest a potential link between CGRP involvement in immune responses and an increased risk of infection.
Purpose of the Study:
- To systematically evaluate whether CGRP-targeting therapies are associated with an increased risk of infections.
- To analyze the incidence of infectious adverse events across various CGRP antagonists used in clinical practice.
Main Methods:
- Conducted a systematic review and network meta-analysis of 37 randomized placebo-controlled trials.
- Included data from 22,518 patients treated with CGRP antagonists (erenumab, fremanezumab, galcanezumab, eptinezumab, atogepant, rimegepant).
- Assessed the relative risk and number needed to harm for infectious adverse events and serious adverse events.
Main Results:
- Preventive CGRP-targeting therapies showed a mild increase in infection risk (RR 1.08).
- Galcanezumab and eptinezumab were individually associated with increased infection risk at specific doses.
- Fremanezumab had the fewest serious infectious adverse events, while erenumab had the highest incidence.
Conclusions:
- Preventive CGRP pathway antagonists, particularly eptinezumab and galcanezumab, may slightly elevate infection risk.
- The clinical impact is likely minimal for most migraine patients due to a high number needed to harm and low effect size.
- Increased infection risk may be more pronounced in immunocompromised individuals or at a public health level.
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