The anti-CGRP antibody fremanezumab reduces migraine frequency and medication overuse in patients trapped in a cycle of headache and painkiller overuse.
High MOH reversion rate at 1 yearReal-world studies showed that many patients who had been trapped in a cycle of medication overuse were able to break free after a year of fremanezumab treatment.
What the researchers found
Fremanezumab, an anti-CGRP monoclonal antibody, effectively reduced migraine frequency, acute medication use, and headache-related disability in adults with migraine complicated by medication overuse. Clinical trial post hoc analyses showed significant reductions in monthly migraine days, acute headache medication use days, and HIT-6 disability scores compared to placebo over 12 weeks. Real-world studies demonstrated sustained reductions in monthly headache days at 6 months and a high reversion rate from medication overuse headache after one year of treatment.
Why it matters
Medication overuse headache is a vicious cycle where the very drugs used to treat migraines end up making them worse. This review shows that fremanezumab — which works by blocking the CGRP peptide pathway rather than simply masking pain — can break this cycle, reducing both migraine frequency and the reliance on overused medications. This is particularly important because these patients are among the hardest to treat.
The numbers in context
n=1,422 · 2 clinical trials + 7 real-world studies · 176 records screened · 12-week trial periods · 6-month and 1-year real-world follow-up · reduced monthly migraine days, medication use, and HIT-6 scores
How the study worked
This systematic review searched PubMed and Embase databases for studies on fremanezumab in adults with migraine complicated by medication overuse. From 176 records, 2 clinical trials and 7 real-world studies were included. Randomized controlled trials were assessed for bias using the Cochrane RoB 2 tool, and real-world studies were evaluated using ROBINS-I and ROB-ME tools.
Who was studied
Adults with migraine complicated by medication overuse
What this study cannot tell us
Most efficacy data came from post hoc analyses of clinical trials rather than pre-specified primary endpoints for this population. The overall quality of evidence was limited, and real-world studies lacked standardized reporting criteria. More robust prospective studies are needed to confirm long-term benefits.
How to read the evidence
This is a systematic review combining 2 clinical trials and 7 real-world studies, but the clinical trial data came from post hoc analyses rather than pre-specified endpoints. The overall evidence quality is moderate, limited by the lack of randomized trials specifically designed for medication overuse headache patients.
When this study was published
Published in 2025 with searches updated through June 2024, this review reflects the current state of evidence for fremanezumab in medication overuse headache.
The bigger picture
Anti-CGRP therapies represent a paradigm shift in migraine treatment because they target the underlying peptide signaling rather than just providing acute pain relief. This review extends their evidence base to one of the most challenging migraine populations — those with medication overuse — and supports the idea that peptide-targeted prevention can succeed where traditional approaches have failed.
Questions still open
- How does fremanezumab compare to other anti-CGRP antibodies (erenumab, galcanezumab) specifically in medication overuse headache patients?
- What is the optimal duration of fremanezumab treatment before attempting to discontinue in patients who have reverted from medication overuse headache?
- Could early initiation of anti-CGRP therapy prevent the development of medication overuse headache in high-risk migraine patients?
Common questions
What is CGRP and why is blocking it helpful for migraines?
What is medication overuse headache and why is it so hard to treat?
Read the original research
Fremanezumab for the Treatment of Migraine Complicated by Medication Overuse: A Systematic Review.
Clinical drug investigation, 45(5), 247-254
Citation
Hajjaj, Ibrahim; Baraldi, Carlo; Pellesi, Lanfranco. (2025). Fremanezumab for the Treatment of Migraine Complicated by Medication Overuse: A Systematic Review.. Clinical drug investigation, 45(5), 247-254. https://doi.org/10.1007/s40261-025-01433-y