See a virtual headache specialist in 1-2 days! Get HALF off your first month!

IT's BACK: TorqueGlide (with cannabinoids) is now in stock!

Migraine Book on Amazon

New Safety Insights from CGRP Antibody Study

Posted on June 01 2025, By: Cerebral Torque

← Back to Migraine Resource Hub
This content is sponsored by

New Safety Insights from CGRP Antibody Study

An analysis of 14,285 safety reports reveals new potential signals for eptinezumab while confirming excellent overall safety for all four CGRP antibodies
Study Published in Headache • May 2025

Read the complete research study:

View Full Study in Headache Journal

Study Overview

A new pharmacovigilance study published in Headache: The Journal of Head and Face Pain has analyzed safety data from the European Union's EudraVigilance database for all four FDA-approved CGRP monoclonal antibodies. 

14,285
Total Safety Reports
From EudraVigilance database across all four antibodies
15
Safety Signals
11 for eptinezumab, 4 for galcanezumab
86%
Female Patients
Consistent with migraine demographics

Understanding Safety Signals and ROR

Safety signals are statistical patterns that suggest a medication might be associated with a particular side effect more often than expected. They don't prove the medication causes the side effect - they indicate areas needing further investigation.

ROR (Reporting Odds Ratio) compares how often a side effect is reported with one medication versus another. An ROR of 6.93 for palpitations means palpitations were reported almost 7 times more often with that medication compared to the comparison drug (topiramate in this study).

Event numbers (like "13 vs 18 events") show the actual reported cases: 13 reports of palpitations with eptinezumab compared to 18 reports with topiramate. Even though topiramate had more total reports, the ROR calculation accounts for the total number of patients taking each drug, showing eptinezumab had disproportionately more palpitation reports relative to its usage.

Most importantly, the analysis confirmed that the vast majority of reported side effects were non-serious and consistent with established safety profiles from clinical trials.

Safety Report Distribution

Reports by Medication
Erenumab (Aimovig) 7,547 reports (53%)
Fremanezumab (Ajovy) 3,241 reports (23%)
Galcanezumab (Emgality) 2,996 reports (21%)
Eptinezumab (Vyepti) 501 reports (3%)

The distribution reflects approval timelines and usage patterns. Erenumab, approved first in 2018, accounts for over half of all reports. Eptinezumab's smaller representation reflects its more recent European approval (2022) and intravenous administration limiting broader use.

Confirmed Expected Side Effects

The study validated known side effect patterns that align with clinical trial data:

Erenumab: Constipation remained the most distinctive side effect, reported in over 1,000 cases. This gastrointestinal effect reflects erenumab's unique mechanism as a CGRP receptor blocker.

Injection Site Reactions: All three subcutaneous antibodies (fremanezumab, galcanezumab, erenumab) showed expected local reactions including pain, redness, and swelling.

Allergic Reactions: Skin reactions like pruritus and urticaria appeared across all antibodies, reflecting normal immune responses to protein medications.

New Safety Signals for Eptinezumab

The study's most significant finding was identifying 11 potential new safety signals for eptinezumab that hadn't been clearly recognized in clinical trials. These signals warrant further investigation to determine clinical significance.

Palpitations
ROR: 6.93
13 vs 18 events
Oropharyngeal Pain
ROR: 7.19
12 vs 16 events
Erythema (Skin Redness)
ROR: 12.31
9 vs 7 events
COVID-19 Association
ROR: 9.62
15 vs 15 events
Migraine Reports
ROR: 3.94
78 vs 197 events

Understanding the COVID-19 Signal

The COVID-19 association is one of the more puzzling findings. Despite equal case numbers (15 each for eptinezumab and topiramate), the ROR of 9.62 suggests eptinezumab patients were statistically more likely to have COVID-19 reported as an adverse event. Possible explanations include reporting artifacts from IV infusion settings requiring more frequent COVID testing, theoretical immune system effects from CGRP blockade, or statistical coincidence with small numbers. Clinical trials didn't show increased infection rates, and this finding requires further investigation to determine if it represents a real association or statistical artifact.

Additional eptinezumab signals identified: The study found 6 additional statistically significant signals including anaphylactic reaction (ROR: 42.05), pruritus (ROR: 11.45), hypersensitivity (ROR: 4.19), throat irritation (ROR: 36.09), nasal congestion (ROR: 15.98), and influenza-like illness (ROR: 16.74). Most of these represent allergic or infusion-related reactions consistent with intravenous protein administration.

Cardiovascular Considerations

The palpitations signal for eptinezumab is noteworthy because cardiovascular effects have emerged as a potential class concern. Previous studies have noted hypertension, Raynaud's phenomenon, and other cardiovascular events across different CGRP antibodies.

Importantly, palpitations were also statistically significant for erenumab and galcanezumab, suggesting this might represent a class-wide effect rather than being specific to eptinezumab. This aligns with CGRP's known cardiovascular protective functions.

Why More Signals for Eptinezumab?

Several factors may explain eptinezumab's additional signals: intravenous administration in healthcare settings leads to closer monitoring and more immediate reporting; the controlled environment allows detection of effects that might be missed with home injections; and potential pharmacological differences in tissue distribution or metabolism.

Throat Pain Mechanism

The oropharyngeal pain signal is interesting because CGRP is present in sensory nerves of the upper airways. Blocking CGRP might disrupt normal sensory functions in this area, leading to altered pain perception. This finding was also noted in a previous FDA database analysis, strengthening the signal.

Reassuring Overall Safety Profile

Despite identifying new potential signals, the study's conclusions remain reassuring for patients and providers. The analysis confirmed that CGRP antibodies maintain excellent safety profiles in real-world use.

1
Serious Safety Signal
Anaphylactic reactions - already known and labeled
Most
Side Effects
Were non-serious and matched clinical trial data

The only serious safety signal was anaphylactic reactions with eptinezumab, already recognized and included in prescribing information. Healthcare providers monitor for allergic reactions during IV infusions, with emergency treatments readily available.

Class Effects vs. Individual Differences

The study revealed both shared class effects and medication-specific patterns. Cardiovascular signals appeared across multiple antibodies, suggesting potential class-wide effects related to CGRP's cardiovascular functions. However, the distribution and intensity of signals varied between medications, indicating important individual differences.

The Migraine Signal Paradox

One finding was "migraine" appearing as a safety signal. This likely represents treatment failure rather than medication-induced migraines. When preventive medications don't work effectively, continued migraine attacks might be reported as adverse events, creating this statistical association.

Specific guidance by medication

Specific guidance by medication:

Eptinezumab patients: Be aware of potential throat discomfort after infusions and report any heart palpitations or racing to your provider.

All CGRP antibody patients: Report any new or concerning cardiovascular symptoms, though these appear uncommon based on the data.

CGRP antibodies continue to demonstrate excellent safety profiles in real-world use. These findings enhance our understanding and ability to monitor for potential effects, but don't change the fundamental assessment that these are safe, effective medications for migraine prevention.

Future Research Priorities

The findings highlight the need for dedicated cardiovascular safety studies, investigation of the throat pain mechanism with eptinezumab, and long-term follow-up studies to better characterize the safety profile in broader patient populations including those with comorbidities.

Read the complete research study:

Read Full Study in Headache Journal
Disclaimer

This article is for educational purposes only and is not intended to replace professional medical advice, diagnosis, or treatment. Always consult with qualified healthcare providers regarding your specific medical conditions and treatment options. Do not stop, start, or change any medications without first discussing with your healthcare provider. If you experience concerning side effects with any CGRP antibody, contact your healthcare provider promptly.

MigraineScience Blog

Join Our Community