Switching OnabotulinumtoxinA and Monoclonal Antibodies Anti-CGRP in Severe, Drugs-Resistant Chronic Migraine

Abstract text (incl. figure legends and references)

Question: To assess the long-term therapeutic impact of anti-calcitonin gene related protein (CGRP) monoclonal antibodies (anti-CGRP mAbs) in drugs-resistant patients with chronic migraine (CM) with no or partial response to OnabotulinumtoxinA (BTX).

Methods: A retrospective, cohort study, enrolling 78 severe CM patients (>80% with medication-overuse [MO]), resistant to ≥3 preventative treatments, and treated with BTX and then with anti-CGRP mAbs. The study consisted of two observational periods of 9 months. A varying non-observational period of at least 6-months occurred after the last BTX treatment. The primary endpoints were the absolute change from baseline in monthly headache days (MHDs), response rates and persistence in MO at 3-, 6- and 9-months follow-up in the two cohorts separately. The secondary endpoint was the change in acute medications use per month. Finally, we performed a last observation carried forward analysis for primary and secondary endpoints.

Results: After nine months of treatment, retention rate ranged from 91.0% to 62.2% in the BTX-A cohort and from 96.2%, to 76.9% in the anti-CGRP mAbs cohort (fig.1). Approximatively 20% of patients discontinued both treatments due to inefficacy. After 9 months of treatment, 22.4% with BTX-A and 65.0% with anti-CGRP mAbs achieved a ≥50% response (fig.2). Two patients were migraine-free in the CGRP cohort. BTX-A and anti-CGRP mAbs reduced MHDs at month-9.0 by -5.0 and -12.0, respectively, and decreased the number of MO patients at month-9 (75.5% and 25% persisted in MO, respectively [fig. 3]). Only two patients discontinued treatments due to AEs.

Conclusions: Our findings in drugs-resistant CM patients indicate that patients who discontinued BTX-A undergoing anti-CGRP mAbs treatment showed a substantial clinical improvement in migraine related outcomes. Stopping BTX-A in patients with no response/partial response after the first two cycles and switching to an anti-CGRP mAb appears a viable option.