Discontinuing Monoclonal Antibodies Targeting CGRP Pathway After One-Year Treatment: An Observational Longitudinal Cohort Study

Abstract Background : The monoclonal antibodies anti-calcitonin gene-related peptide (mAbs anti-CGRP) pathway revolutionized migraine prevention. However, some drug agencies limited the treatment to one year due to their high costs. This study aimed at evaluating the effect of discontinuing mAbs anti-CGRP on monthly migraine days (MMDs) and disability in high-frequency episodic (HFEM) and chronic migraine (CM) patients. Methods : This observational longitudinal cohort study was conducted at 10 Italian headache centres (November 2019-July 2021). Consecutive adult patients followed up for three months (F-UP1-3) after discontinuation of a one-year erenumab/galcanezumab treatment were enrolled. The primary endpoint was the change in F-UP MMDs. Secondary endpoints included variation in pain intensity (Numerical Rating Scale, NRS), monthly painkiller intake (MPI), and HIT-6 scores. We also assessed from F-UP1 to 3 the ≥50% response rates (RR), relapse rate to CM, and recurrence of Medication Overuse (MO). Results : We enrolled 154 patients (72.1% female, 48.2±11.1 years, 107 CM, 47 HFEM); 91 were treated with erenumab, 63 with galcanezumab. From F-UP1 to F-UP3, MMDs, MPI, NRS, and HIT-6 progressively increased but were still lower at F-UP 3 than baseline (Friedman's analysis of rank, p<.001). In the F-UP 1-3 visits, ≥50%RR frequency did not differ significantly between CM and HFEM patients. However, the median reduction in RR at F-UP3 was higher in HFEM (-47.7% [25th, -79.5; 75th ,-17.0]) than in CM patients (-25.5% [25th, -47.1; 75th ,-3.3]; Mann-Whitney U test; p=.032). Of the 84 baseline CM patients who had reverted to EM, 28 (33.3%) relapsed to CM at F-UP1, 35 (41.7)% at F-UP2, 39 (46.4%) at F-UP3. Of the 64 baseline MO patients ceasing MO, 15 (18.3%) relapsed to MO at F-UP1, 26 (31.6%) at F-UP2, and 30 (42.3%, 11 missing data) at F-UP3. Lower MMDs, MPI, NRS, and HIT-6 and higher RR in the last month of therapy characterized patients with 50% RR at F-UP1 and F-UP3 (Mann-Whitney U test; consistently p<.01). Conclusion : Migraine frequency and disability gradually increased after anti-CGRP mAbs interruption. Most patients did not relapse to MO or CM despite the increase in MMDs. Our data suggest to reconsider mAbs anti-CGRP discontinuation.