A phase 3, randomised, placebo-controlled study of erenumab for the prevention of chronic migraine in patients from Asia: the DRAGON study

Abstract

Abstact Background DRAGON was a phase 3, randomised, double-blind, placebo-controlled study which evaluated the efficacy and safety of erenumab in patients with chronic migraine (CM) from Asia not adequately represented in the global pivotal CM study. Methods DRAGON study was conducted across 9 Asian countries or regions including mainland China, India, the Republic of Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. Patients (N = 557) with CM (aged 18–65 years) were randomised (1:1) to receive once-monthly subcutaneous erenumab 70 mg or matching placebo for 12 weeks. The primary endpoint was the change in monthly migraine days (MMD) from baseline to the last 4 weeks of the 12-week double-blind treatment phase (DBTP). Secondary endpoints included achievement of ≥ 50% reduction in MMD, change in monthly acute headache medication days, modified migraine disability assessment (mMIDAS), and safety. Study was powered for the primary endpoint of change from baseline in MMD. Results At baseline, the mean (SD) age was 41.7 (± 10.9) years, and 81.5% (n = 454) patients were women. The mean migraine duration was 18.0 (± 11.6) years, and the mean MMD was 19.2 (± 5.4). 97.8% (n = 545) randomised patients completed the DBTP. Overall, demographics and baseline characteristics were balanced between the erenumab and placebo groups except for a slightly higher proportion of women in the placebo group. At Week 12, the adjusted mean change from baseline in MMD was − 8.2 days for erenumab and − 6.6 days for placebo, with a statistically significant difference for erenumab versus placebo (adjusted mean difference vs placebo: − 1.57 [95%CI: − 2.83, − 0.30]; P = 0.015). A greater proportion of patients treated with erenumab achieved ≥ 50% reduction in MMD versus placebo (47.0% vs 36.7%, P = 0.014). At Week 12, greater reductions in monthly acute headache medication days (− 5.34 vs − 4.66) and mMIDAS scores (− 14.67 vs − 12.93) were observed in patients treated with erenumab versus placebo. Safety and tolerability profile of erenumab was comparable to placebo, except the incidence of constipation (8.6% for erenumab vs 3.2% for placebo). Conclusion DRAGON study demonstrated the efficacy and safety of erenumab 70 mg in patients with CM from Asia. No new safety signals were observed during the DBTP compared with the previous trials. Trial registration NCT03867201

Adverse and serious adverse events incidence of pharmacological interventions for managing chronic and episodic migraine in adults: a systematic review

“…Out of 19 111 initial records after removal of duplicates, 18 777 were excluded during title and abstract screening. Three-hundred and thirty-four records were assessed for eligibility and 59 articles reporting data from 33 trials were included after full text assessment (see online supplemental appendix 2 for excluded studies) 19–57. Although many of these linked articles were cited, we only used the main trial paper for the main citation, as the other linked papers only reported some subgroup analyses, were either repetitive or combined the data.…”

“…The patients in each of the included studies satisfied the diagnostic criteria of chronic or episodic migraine in accordance with the International Classification of Headache Disorders 58. Nineteen RCTs included only participants with episodic migraine,19 21 36–45 47–49 51–53 55 nine RCTs enrolled participants exclusively with chronic migraine,20 22–26 29–31 35 57 and five RCTs had a mixed population of both chronic or episodic migraine participants 34 46 50 54 56. All of the RCTs were conducted across multiple centres.…”

“…Most of the trials utilised double-blinded designs except two trials that were classed as open-label 35 55. Treatment duration varied across the trials; one trial had a 4-week treatment duration,52 while 19 trials reported 12 weeks 20–22 29–31 34 36 37 39 40 42 47–51 53 57. Additionally, one trial had a treatment duration of 22 weeks,41 11 trials reported a 24-week treatment duration,21 25 26 35 38 43–46 54 56 and for one trial the treatment duration was 52 weeks 55…”

“…Thirty-two studies reported adverse events for 20 different dosing regimens of nine drugs with 21 780 participants 19–57. The most reported adverse events belonged to Amitriptyline 25 mg to 100 mg and galcanezumab 150 mg with 89%39 41 and 72.0%,39 respectively.…”

“…Serious adverse events were reported in 33 trials, evaluating 20 different dosing regimens of nine drugs with data from 22 615 participants 19–57. One trial did not report the number of people with SAEs, but the results indicated no treatment-related SAEs 49.…”