Anti-CGRP Migraine Antibodies Are Safe and Effective When Combined with Other Biologic Drugs | Research

The takeaway

Anti-CGRP migraine antibodies remained safe and effective when used alongside other monoclonal antibodies for different diseases, with only mild side effects in 15.8% of patients.

15.8% mild AEs from combination
Only 6 of 38 patients experienced mild adverse events from combining anti-CGRP antibodies with other biologics, and only 1 discontinued due to side effects.

What the researchers found

Anti-CGRP monoclonal antibodies were safe and effective when used alongside other monoclonal antibodies for different conditions. In 38 migraine patients taking both an anti-CGRP mAb and another mAb, monthly headache days decreased significantly at 3 months (p<0.0001) and 6 months (p<0.001), along with improvements in disability (MIDAS) and impact (HIT-6) scores. Only 15.8% of patients experienced mild adverse events from the combination, and only one patient discontinued due to side effects. At 6 months, 48.3% of patients reported meaningful improvement on the global impression of change scale.

Why it matters

Many migraine patients also have other conditions requiring monoclonal antibody therapy (e.g., autoimmune diseases, cancer). Until now, there was almost no data on whether combining anti-CGRP antibodies with other biologics was safe. This real-world study provides reassuring evidence that these combinations are well tolerated, allowing patients to receive optimal treatment for multiple conditions simultaneously without compromising migraine management.

The numbers in context

n=38 · MHDs decreased at 3 months (p<0.0001) · MHDs decreased at 6 months (p<0.001) · 48.3% PGIC ≥5 at 6 months · 15.8% mild AEs · 1 discontinuation for AEs · 71.1% added anti-CGRP to existing mAb

How the study worked

This multicenter prospective cohort study used data from the Italian Headache Registry. Patients receiving both an anti-CGRP monoclonal antibody and another monoclonal antibody for a different disease were followed for 6 months. Effectiveness was measured by monthly headache days, MIDAS disability score, HIT-6 impact score, and patient global impression of change. Adverse events were systematically recorded.

Who was studied

38 migraine patients receiving concomitant anti-CGRP and other monoclonal antibody therapy, from the Italian Headache Registry

What this study cannot tell us

The sample size of 38 patients is small, limiting statistical power for detecting rare adverse events from the combination. There was no control group of patients taking anti-CGRP mAbs alone. The study did not detail which specific other monoclonal antibodies were used or for which conditions. The 6-month follow-up may be insufficient to detect long-term safety concerns from dual biologic therapy.

How to read the evidence

This is a prospective real-world cohort study from a multicenter registry. While prospective data collection is a strength, the small sample size (n=38) and lack of a control group limit the conclusions. It provides valuable safety signal data but not definitive evidence.

When this study was published

Published in 2024, this is one of the first studies to address the safety of combining anti-CGRP antibodies with other biologics, reflecting a growing clinical reality as more patients receive multiple biologic therapies.

The bigger picture

As biologic therapies become increasingly common across medicine — from migraine to autoimmune diseases to cancer — the question of whether these drugs can be safely combined is critical. This study provides early evidence that anti-CGRP peptide-targeting antibodies don't cause problematic interactions with other biologics, a finding that will become increasingly important as the population of patients on multiple biologic therapies grows.

Questions still open

Do specific anti-CGRP and other mAb combinations have different safety profiles, or is the safety consistent across all pairings?
Could combining anti-CGRP antibodies with certain biologics actually enhance migraine treatment through complementary mechanisms?
What are the long-term immunological effects of blocking CGRP signaling while also modifying other immune pathways?

Common questions

What are anti-CGRP antibodies and why might patients need another biologic too?

Anti-CGRP antibodies (like erenumab, fremanezumab, galcanezumab) are migraine prevention drugs that block the CGRP peptide involved in migraine pain. Many migraine patients also have other conditions — like rheumatoid arthritis, psoriasis, or inflammatory bowel disease — that are treated with different biologic drugs. This study looked at whether using both types simultaneously is safe.

Were there any serious side effects from combining the biologics?

No serious adverse events were reported. Only 6 patients (15.8%) experienced mild side effects from the combination, and just 1 patient discontinued treatment because of them. This is a reassuring safety profile, though the small study size means very rare side effects could be missed.

Read the original research

Association of anti-calcitonin gene-related peptide with other monoclonal antibodies for different diseases: A multicenter, prospective, cohort study.

European journal of neurology, 31(12), e16450

View on PubMed ↗Publisher’s paper ↗

Citation

Iannone, Luigi Francesco; Romozzi, Marina; Russo, Antonio; Saporito, Gennaro; De Santis, Federico; Ornello, Raffaele; Sances, Grazia; Vaghi, Gloria; Tassorelli, Cristina; Albanese, Maria; Guerzoni, Simona; Casalena, Alfonsina; Vollono, Catello; Calabresi, Paolo; Prudenzano, Maria Pia; Mampreso, Edoardo; Volta, Giorgio Dalla; Valente, Maria Rosaria; Avino, Gianluca; Chiarugi, Alberto; Sacco, Simona; Pistoia, Francesca. (2024). Association of anti-calcitonin gene-related peptide with other monoclonal antibodies for different diseases: A multicenter, prospective, cohort study.. European journal of neurology, 31(12), e16450. https://doi.org/10.1111/ene.16450