Rippon, Gregory A.

Objective To determine reversion rates from chronic migraine to episodic migraine during long-term erenumab treatment. Methods A daily headache diary was completed during the 12-week, double-blind treatment phase of a placebo-controlled trial comparing erenumab 70 mg, 140 mg, and placebo, and weeks 1–12, 21–24, 37–40, and 49–52 of the open-label treatment phase. Chronic migraine to episodic migraine reversion rates were assessed over the double-blind treatment phase; persistent reversion to episodic migraine over 24 weeks (double-blind treatment phase through the first 12 weeks in the open-label treatment phase), long-term persistent reversion to episodic migraine over 64 weeks (double-blind treatment phase plus open-label treatment phase); delayed reversion to episodic migraine through the first 12 weeks of the open-label treatment phase among patients remaining in chronic migraine during the double-blind treatment phase. Results In the double-blind treatment phase, 53.1% (95% confidence interval: 47.8–58.3) of 358 erenumab-treated completers had reversion to episodic migraine; monthly reversion rates to episodic migraine were typically higher among patients receiving 140 mg versus 70 mg. Among 181 completers (receiving erenumab for 64 weeks), 98 (54.1% [95% confidence interval: 46.6–61.6]) had reversion to episodic migraine during the double-blind treatment phase; of those, 96.9% (95% confidence interval: 91.3–99.4) had persistent reversion to episodic migraine, 96.8% (95% confidence interval: 91.1–99.3) of whom had long-term persistent reversion to episodic migraine. Delayed reversion to episodic migraine occurred in 36/83 (43.4% [95% confidence interval: 32.5–54.7]) patients; of these, 77.8% (95% confidence interval: 60.9–89.9) persisted in reversion through week 64. Conclusions Patients with reversion to episodic migraine at week 12 will likely persist as episodic migraine with longer-term erenumab; others may achieve delayed reversion to episodic migraine. Clinical trial registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02066415

Background Previously published three-month placebo-controlled and one-year open-label clinical trial data have provided information on the efficacy and safety of erenumab. Methods Interim analysis was undertaken from an ongoing five-year open-label treatment phase after all patients completed three years in the open-label treatment phase or discontinued the study. Adult patients with episodic migraine enrolled in the open-label treatment phase initially received 70 mg erenumab monthly. A protocol amendment increased the dosage to 140 mg monthly to assess long-term safety of the higher dose. Safety and tolerability were assessed by monitoring adverse events, electrocardiograms, laboratory assessments, and vital signs. Results Of 383 patients enrolled in the open-label treatment phase, at data cutoff 235 (61.3%) remained in the study, all received 140 mg for ≥1 year. Median (Q1, Q3) exposure (70 or 140 mg) for all patients enrolled was 3.2 (1.3, 3.4) years. The most frequent adverse events (≥4.0/100 patient-years) were reported as viral upper respiratory tract infection, sinusitis, influenza, and back pain. Exposure-adjusted serious adverse event rates were 4.2/100 patient-years. There was no increase in cardiovascular events over time. Conclusions In this long-term study of a CGRP-receptor antibody, erenumab was found to be safe and well-tolerated with a spectrum and rate of adverse events consistent with shorter-term placebo-controlled studies. Trial registration ClinicalTrials.gov NCT01952574