Anti-CGRP monoclonal antibodies consistently reduced monthly migraine days by about 12-13 days across three consecutive years of treatment, though 61.5% of patients still did not achieve a 50% response by year three.
-12.9 migraine days/monthsustained reduction at year 3, consistent with years 1 and 2, in 179 patients with predominantly chronic migraine
What the researchers found
Monthly migraine days were reduced consistently across three one-year treatment cycles: -12.7 days in year 1, -12.4 days in year 2, and -12.9 days in year 3. Baseline migraine days progressively decreased across cycles from 21.1 to 19.0 to 15.9, while residual migraine days decreased from 9.6 to 9.6 to 8.5.
At the end of year 3, the 50% response rate was 38.5% (69/179 patients) in this intention-to-treat analysis. The sustained reduction in monthly migraine days confirms long-term effectiveness, but the remaining high burden of disease in many patients underscores the need for additional treatment approaches and exploration of non-CGRP pathways.
Why it matters
Most anti-CGRP antibody clinical trials lasted only 3-6 months. This 3-year real-world study provides crucial long-term effectiveness data showing the drugs maintain their benefit without wearing off. The conservative intention-to-treat approach also gives a realistic picture of outcomes, including patients who discontinued — important for setting clinical expectations.
How the study worked
This was a prospective, real-world, intention-to-treat study enrolling 179 patients who started anti-CGRP monoclonal antibodies between 2018 and 2020. Clinical data were recorded using prospectively filled headache diaries across three consecutive one-year treatment cycles. Analysis used a multivariate linear mixed model including the entire enrolled population, regardless of whether they completed all cycles.
What this study cannot tell us
This is an observational study without a control group, so natural fluctuations in migraine frequency cannot be fully accounted for. The 38.5% response rate at year 3 includes all enrolled patients (intention-to-treat), including those who discontinued, which is conservative but may underestimate effectiveness in patients who tolerate the treatment. Specific anti-CGRP antibodies used were not differentiated in the abstract. The cohort was primarily chronic migraine with medication overuse, limiting generalizability.
How to read the evidence
This is a prospective real-world observational study with intention-to-treat analysis over three years. While lacking a control group, the prospective design, diary-based outcome tracking, and conservative ITT approach provide meaningful long-term effectiveness data.
When this study was published
Published in 2025 with patients enrolled between 2018-2020, this study provides some of the longest real-world follow-up data available for anti-CGRP monoclonal antibody treatment.
The bigger picture
Anti-CGRP monoclonal antibodies have transformed migraine prevention, but long-term real-world data has been limited. This study confirms sustained effectiveness over three years while honestly revealing that a majority of treated patients still carry significant migraine burden. This supports the growing recognition that CGRP is not the only pathway driving chronic migraine, and multi-target or combination approaches may be needed.
Questions still open
- Why do over 60% of patients fail to achieve a 50% response despite consistent reductions in migraine days?
- Would combining anti-CGRP antibodies with treatments targeting other pathways improve response rates?
- Do the specific anti-CGRP antibodies (erenumab, fremanezumab, galcanezumab) differ in long-term effectiveness?
Common questions
Do anti-CGRP migraine drugs stop working over time?
Why didn't more patients achieve a 50% reduction in migraine?
Read the original research
Real world effectiveness of anti-CGRP monoclonal antibodies over three consecutive one-year treatment cycles: An intention-to-treat analysis.
Cephalalgia : an international journal of headache, 45(8), 3331024251353421
Citation
Vaghi, Gloria; Corrado, Michele; Pocora, Maria Magdalena; Bighiani, Federico; Cammarota, Francescantonio; Antoniazzi, Alessandro; Costantino, Luca; Martinelli, Daniele; Allena, Marta; Ghiotto, Natascia; Guaschino, Elena; Bottiroli, Sara; Iannone, Luigi Francesco; De Cesaris, Francesco; Montisano, Danilo Antonio; Grazzi, Licia; Sances, Grazia; Montomoli, Cristina; Tassorelli, Cristina; De Icco, Roberto. (2025). Real world effectiveness of anti-CGRP monoclonal antibodies over three consecutive one-year treatment cycles: An intention-to-treat analysis.. Cephalalgia : an international journal of headache, 45(8), 3331024251353421. https://doi.org/10.1177/03331024251353421