Abstract text (incl. figure legends and references)

Question: To assess the long-term effects of discontinuation and retreatment of anti-CGRP mAbs in resistant chronic migraine (CM) patients.

Methods: A monocentric prospective cohort study, enrolling 53 severe (resistant to ≥3 preventive treatments) CM patients (96.2% with medication-overuse [MO]), treated with erenumab, galcanezumab or fremanezumab for 12-months, who discontinued and re-started treatment (fig.1). The primary outcome was the percentage of patients that maintained a sustained clinical response after six months of discontinuation. The clinical effectiveness was evaluated using monthly migraine days (MMDs), response rates and acute medications use. Secondary outcomes were the effect of re-treatment up to three months, using the same parameters reported for the primary outcome.

Results: After 6 months of discontinuation only 8 patients (15.1%) achieved a sustained response without treatment. At month-3 after discontinuation, most patients (38, 71.7%) had already restarted treatment, mainly after the mandatory period of discontinuation (1 to 3 months [34, 64.2%]) (fig.2). Patients with a sustained response compared to patients who restarted therapy showed less MO at baseline (75% vs 100% p=0.02) and reduced MMDs (10.6±7.8 vs 3.8±2.4, p=0.010), days with analgesic use (9.8±7.7 vs 3.6 ±2.6, p=0.014) and lower MIDAS score (24.2±24.6 vs 7.8±16.3, p=0.001) at month-12 of treatment, respectively. Patients re-treated for 3-months (n=39, 73.5%), reported an amelioration in all outcome measures regaining a response similar to that observed at the end of treatment. However, 6 patients (15.3%) did not show any amelioration during retreatment, and one patient withdrawn treatment.

Conclusions: Discontinuing treatment after 12 months did not provide long term benefits and appeared unnecessary in most patients. Two small subgroups of patients reported sustained benefit during discontinuation or, contrariwise, a worsening in MMDs during the second treatment cycle.