False nonresponders to anti-calcitonin gene-related peptide monoclonal antibodies: A real-world analysis beyond migraine frequency reduction.

OBJECTIVES/

backgroundReimbursement criteria for anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (MAbs) typically rely on predefined reductions in monthly migraine days (MMD). However, this approach may fail to capture the full spectrum of treatment benefits, potentially leading to premature discontinuation in patients experiencing meaningful improvements in other parameters.

methodsThis was a retrospective observational cohort study of prospectively collected data from a multicenter headache unit (Hospital Universitari de Bellvitge and Hospital de Viladecans, Barcelona, Spain) between December 2019 and September 2024. We included patients with migraine who initiated anti-CGRP MAbs and who, at 6 months, would not meet institutional reimbursement criteria for response (≥50% reduction in MMD or ≥30% reduction in MMD with ≥1-point Headache Impact Test-6 improvement) but nonetheless continued treatment ("false nonresponders"). As a comparison group, we included patients who discontinued treatment within the first 6 months due to lack of efficacy ("true nonresponders"). Outcome measures included headache frequency, disability, analgesic use, and overall treatment perception, assessed via headache diaries and patient-reported outcomes.

resultsOf 415 patients initiating MAbs, 106 were classified as false nonresponders. By month 6, 91.5% (95% confidence interval [CI] = 84.5-96.0) demonstrated improvements in at least one assessed outcome. Some of the most frequent benefits were Migraine Disability Assessment Score improvement (60.2%, 95% CI = 49.5-70.2), Patient Global Impression of Change score ≥ 5 (54.5%, 95% CI = 44.2-64.6), Headache Impact Test-6 reduction (44.1%, 95% CI = 34.3-54.3), medication-overuse headache resolution (46.4%, 95% CI = 33.0-60.3), chronic to episodic migraine conversion (41.2%, 95% CI = 27.6-55.9), and a reduction in ≥50% of severe intensity days (29.3%, 95% CI = 19.4-41.0). Additionally, 82 patients continued treatment until 12 months, when 18.3% (95% CI = 10.6-28.4) of those eventually met reimbursement criteria, underscoring the potential for late response. In contrast, 76 patients were classified as true nonresponders for discontinuing treatment within the first 6 months; among the 38 who reached the month 6 evaluation, only 65.8% (95% CI = 48.6-80.4) demonstrated improvement in at least one parameter. Compared to false nonresponders, they had a more severe baseline profile, including higher frequency and intensity, greater disability and analgesic use, poorer quality of life, higher depression rates, and more frequent prior onabotulinumtoxinA use.

conclusionA substantial proportion of patients with migraine classified as nonresponders to anti-CGRP MAbs at 6 months show measurable improvements beyond frequency reduction. These "false nonresponders" may benefit from continued treatment, highlighting the need for a more comprehensive assessment that includes intensity, analgesic use, disability, and quality of life to prevent premature discontinuation of potentially effective therapies. Conversely, patients with a worse baseline profile and limited early improvement may be appropriately identified as true nonresponders, justifying early treatment discontinuation.