Randomized trial testing anti-CGRP drug fremanezumab for complex regional pain syndrome—protocol published | Research

The takeaway

A 60-patient RCT is testing whether fremanezumab (anti-CGRP antibody, 225 mg SC) reduces pain in complex regional pain syndrome over 8 weeks, with CGRP biomarker analysis to guide mechanism-based treatment selection.

First anti-CGRP trial for CRPS
A randomized controlled trial is testing whether migraine drug fremanezumab can treat complex regional pain syndrome—the first formal test of anti-CGRP therapy beyond headache

What the researchers found

60 patients; CRPS 3-36 months duration; fremanezumab 225 mg vs placebo SC; 8 weeks; primary: pain intensity change; secondary: pain relief, clinical signs, CGRP biomarker prediction; proof-of-concept design.

Why it matters

CRPS has no effective treatment and can cause lifelong disability. CGRP-driven neurogenic inflammation is a key pathophysiological mechanism, making anti-CGRP antibodies a rational therapeutic approach.

How the study worked

Randomized, double-blind, placebo-controlled, proof-of-concept trial. 60 adult CRPS patients. 1:1 randomization. 8-week treatment. CGRP biomarker analysis.

What this study cannot tell us

Protocol paper—no results yet. Small sample (60). Short duration (8 weeks). CRPS is heterogeneous. Proof-of-concept, not definitive.

How to read the evidence

Published protocol—no results available. Well-designed proof-of-concept RCT.

When this study was published

Published in 2025; trial ongoing.

The bigger picture

Repurposing migraine drugs for other CGRP-driven pain conditions could expand the therapeutic impact of anti-CGRP antibodies. CRPS is the first non-migraine pain condition to be formally tested.

Questions still open

Will CGRP levels predict fremanezumab response in CRPS?
If effective, would other anti-CGRP drugs work for CRPS?
Could longer treatment duration improve outcomes?

Common questions

Could migraine drugs treat CRPS?

This is being tested right now. CRPS involves neurogenic inflammation driven by CGRP—the same neuropeptide targeted by migraine drugs like fremanezumab. A 60-patient clinical trial is underway to determine if blocking CGRP can reduce CRPS pain. Results are expected soon.

What is CRPS and why is it so hard to treat?

Complex regional pain syndrome develops after limb trauma and causes severe, chronic pain with swelling, color changes, and disability. Current treatments are limited. Because CGRP-driven neurogenic inflammation is a key mechanism, anti-CGRP antibodies used for migraine could potentially help—this trial will provide the first formal evidence.

Read the original research

The Effect of Fremanezumab on Pain in Patients with Complex Regional Pain Syndrome: Study Protocol of a Randomized, Double-Blind, Proof-of-Concept, Placebo-Controlled Trial.

Brain sciences, 15(5)

View on PubMed ↗Publisher’s paper ↗

Citation

Thiyagarajah, Abarajitha; Terkelsen, Astrid Juhl; Birklein, Frank; Finnerup, Nanna Brix; Gylfadottir, Sandra Sif. (2025). The Effect of Fremanezumab on Pain in Patients with Complex Regional Pain Syndrome: Study Protocol of a Randomized, Double-Blind, Proof-of-Concept, Placebo-Controlled Trial.. Brain sciences, 15(5). https://doi.org/10.3390/brainsci15050468