Related Experiment Video
Updated: Jun 26, 2026
Detection and Quantification of Calcitonin Gene-Related Peptide (CGRP) in Human Plasma Using a Modified Enzyme-Linked Immunosorbent Assay
Published on: June 16, 2023
ESTELA-Study: Long-Term Effectiveness and Safety of Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies in
Alba Somovilla1, Iris Fernández-Lázaro1, Josué Pagán2,3
1Headache Unit, Department of Neurology, Health Research Institute, La Princesa University Hospital, Madrid, Spain.
Background:
Anti-CGRP antibodies are effective and safe in real-world migraine management, but guidelines recommend discontinuation after 12-18 months due to limited long-term data and remaining uncertainties regarding optimal treatment duration and sustained safety, highlighting the need for large-scale long-term real-world evidence. This study evaluated their safety and effectiveness in patients treated for ≥2 years.
Methods:
This multicenter retrospective study included patients from 13 headache units who received the same anti-CGRP antibody for ≥24 months, excluding discontinuation periods. Baseline characteristics, monthly headache days (MHD), monthly migraine days (MMD), and adverse events (AEs) were recorded at baseline, 6 months, 1, 2, 3, and 4 years. Descriptive statistics were used to summarize clinical characteristics, and appropriate parametric or non-parametric tests were applied for group comparisons. Multivariate analyses were performed to explore associations between baseline variables and long-term treatment response.
Results:
A total of 454 patients (91% female, mean age 48) were analyzed, with follow-up at 2 years (n = 454), 3 years (n = 135), and 4 years (n = 17). Treatments included erenumab (39%), galcanezumab (34%), and fremanezumab (27%). Fifty-seven percent maintained continuous therapy, while 43% restarted after discontinuation. Sustained reductions in MHD and MMD were observed at 2, 3, and 4 years (MHD from 20 to 6, 6, 5/MMD from 14 to 4, 4, and 2). Medication overuse decreased from 78% to 13%, 20%, and 18%. Loss of effectiveness occurred in 4.2% after 2 years. AEs appeared in <20%, mostly mild (>80%), leading to discontinuation in 0.4%. Multivariate analysis showed that shorter disease duration prior to anti-CGRP initiation, earlier anti-CGRP initiation, and greater MHD/MMD reduction at 6 months were associated with better long-term outcomes.
Conclusions:
Anti-CGRP mAbs demonstrate sustained long-term safety and effectiveness, with consistent reduction in headache and migraine days and lower medication overuse. Early initiation and greater initial improvement predict better long-term outcomes. Findings support extending therapy beyond 12-18 months, supporting optimization of clinical protocols.
