About 29% of migraine patients discontinued anti-CGRP monoclonal antibodies within an average of 9 months, primarily due to ineffectiveness, with most who continued treatment switching to a different anti-CGRP drug.
28.8% Discontinuation RateNearly 1 in 3 migraine patients stopped anti-CGRP antibody treatment, primarily due to ineffectiveness, highlighting the need for better response prediction and alternative CGRP-pathway therapies
What the researchers found
Of 472 patients treated with anti-CGRP/R monoclonal antibodies, 136 (28.8%) discontinued after an average of 9.0 months. Ineffectiveness was the primary reason (70.6%), followed by loss to follow-up (13.1%) and adverse events (7.3%). Most (77.9%) discontinued within the first year. Response rates (≥50% reduction in monthly headache days) were 30.5% at 3 months, 34.6% at 6 months, and 40.0% at 12 months — but only 16.9% were responding in their last month before discontinuation. After stopping, 48.5% started new treatment, with 67.6% of those switching to a different anti-CGRP antibody.
Why it matters
Understanding what happens when anti-CGRP drugs fail is critical for the ~25-30% of patients who don't respond. This study shows that switching between anti-CGRP antibodies is the most common next step — and may be rational, since different drugs target CGRP or its receptor differently. It also highlights a significant unmet need: nearly 40% of discontinuers were lost to follow-up, suggesting many patients may be left without adequate migraine care.
How the study worked
This was a prospective cohort study at the Florence Headache Center in Italy, tracking all migraine patients who discontinued anti-CGRP/R monoclonal antibody treatment. Primary outcomes were reasons for discontinuation and treatment course. Secondary outcomes included changes in monthly headache days, response rates, medication overuse, analgesic use, and MIDAS and HIT-6 disability scores at 3, 6, and 12 months.
What this study cannot tell us
This is a single-center study, which may not represent all patient populations. The 39.7% lost to follow-up after discontinuation limits understanding of long-term outcomes. The study does not compare outcomes between different anti-CGRP antibodies. No biomarker analysis was performed to predict non-response, and the definition of treatment failure was clinical rather than standardized.
How to read the evidence
This is a prospective cohort study from a single specialized headache center, providing good-quality real-world evidence. The prospective design is stronger than retrospective analysis, but single-center data limits generalizability.
When this study was published
Published in 2024, this study reflects current clinical practice with anti-CGRP monoclonal antibodies and provides timely data on real-world treatment patterns.
The bigger picture
Anti-CGRP monoclonal antibodies represent the first migraine-specific preventive therapy class, but this study reveals their real-world limitations. With nearly one-third of patients discontinuing, there's a clear need for next-generation peptide-targeted therapies. The high rate of switching between anti-CGRP drugs suggests that the CGRP pathway remains a valid target even after initial failure, potentially supporting development of more potent or differently targeted CGRP-pathway therapies.
Questions still open
- Can biomarkers predict which migraine patients will not respond to anti-CGRP antibodies?
- Is switching between anti-CGRP antibodies more effective than switching to a completely different drug class?
- What happens to the 40% of patients lost to follow-up — are they receiving adequate migraine care elsewhere?
Common questions
If one anti-CGRP migraine drug doesn't work, should I try another?
How long should I try an anti-CGRP migraine drug before deciding it doesn't work?
Read the original research
Outcomes, unmet needs, and challenges in the management of patients who withdraw from anti-CGRP monoclonal antibodies: A prospective cohort study.
Cephalalgia : an international journal of headache, 44(11), 3331024241273968
Citation
Burgalassi, Andrea; Romozzi, Marina; Vigani, Giulia; De Icco, Roberto; Raffaelli, Bianca; Boccalini, Alberto; De Cesaris, Francesco; Calabresi, Paolo; Geppetti, Pierangelo; Chiarugi, Alberto; Iannone, Luigi Francesco. (2024). Outcomes, unmet needs, and challenges in the management of patients who withdraw from anti-CGRP monoclonal antibodies: A prospective cohort study.. Cephalalgia : an international journal of headache, 44(11), 3331024241273968. https://doi.org/10.1177/03331024241273968