When Belgium required migraine patients to take a 3-month break from anti-CGRP antibodies, 86% experienced worsening symptoms — most within the first month — and 45% reported significant anxiety about the interruption.
86% worsenedduring mandatory 3-month CGRP antibody holiday, with 59.4% deteriorating within the first month and significant anxiety reported by 45%
What the researchers found
Among 243 patients across nine Belgian headache clinics: 86.0% reported worsening migraine during the mandatory 3-month treatment holiday, with 59.4% deteriorating within the first month. Only 3.0% improved and 11.0% experienced no change. For 5.9%, worsening extended beyond the 3-month holiday, delaying treatment resumption.
Anxiety about the holiday was reported by 45.0% of patients, with 18.6% experiencing very high anxiety levels. A significant association was found between anxiety and migraine deterioration (p=0.012). Despite the negative impact, 49.1% found the holiday useful for confirming treatment need, and 22.6% found it very useful.
Why it matters
This study provides real-world evidence that mandatory treatment holidays for anti-CGRP antibodies cause significant harm to most patients. As health systems worldwide consider cost-containment measures for expensive biologic therapies, this data shows that rigid interruption policies have real clinical consequences. The findings could influence insurance and regulatory policies in Belgium and other countries considering similar mandates.
How the study worked
Prospective multicenter study of 243 patients from nine Belgian headache clinics receiving erenumab, fremanezumab, or galcanezumab. Participants completed a structured questionnaire during their yearly follow-up visit after the treatment holiday, assessing subjective migraine evolution, anxiety levels, and perceived usefulness of the mandatory break.
What this study cannot tell us
The questionnaire relied on subjective patient reports rather than objective migraine day counts from diaries. The study did not include a control group (patients continuing treatment), so some worsening could reflect natural migraine fluctuation. The association between anxiety and worsening could be bidirectional — anxiety might worsen migraines, or worsening migraines might increase anxiety. Specific anti-CGRP antibody differences were not analyzed separately.
How to read the evidence
This is a prospective multicenter survey study of 243 patients. While it provides valuable real-world patient experience data, it relies on subjective self-report without objective headache diary validation or a control group.
When this study was published
Published in 2025, this study addresses a current and controversial health policy issue affecting migraine patients in Belgium and potentially other countries.
The bigger picture
Anti-CGRP antibodies are expensive biologics, and payers worldwide are exploring strategies to control costs, including mandatory treatment breaks. This Belgian experience provides a real-world test case showing that such policies cause rapid and significant migraine relapse in most patients. The anxiety findings add a psychosocial dimension that policymakers should consider. These results will likely inform ongoing debates about drug holiday policies for migraine biologics in other countries.
Questions still open
- Would a shorter mandatory holiday (e.g., 1 month instead of 3) identify patients who no longer need treatment while causing less harm?
- Could biomarkers predict which patients will remain stable during treatment breaks?
- Do the 3% who improved during the holiday represent patients who could permanently discontinue therapy?
Common questions
Why does Belgium require a break from CGRP migraine treatment?
How quickly do migraines come back after stopping CGRP antibodies?
Read the original research
Migraine treatment with CGRP monoclonal antibodies: patient evaluation of a mandatory treatment holiday in Belgium.
Acta neurologica Belgica, 125(4), 989-998
Citation
De Praeter, Ruben; Tuerlinckx, Evelien; Schoenen, Jean; Boon, Elizabet; Sava, Simona Liliana; Debruyne, Frederik; Delmotte, Koen; De Pauw, Adinda; Van Dycke, Annelies; Van Humbeeck, Cindy; Versijpt, Jan. (2025). Migraine treatment with CGRP monoclonal antibodies: patient evaluation of a mandatory treatment holiday in Belgium.. Acta neurologica Belgica, 125(4), 989-998. https://doi.org/10.1007/s13760-025-02782-3