Early onset of efficacy with erenumab in patients with episodic and chronic migraine

Abstract

BackgroundSubcutaneous erenumab reduced monthly migraine days and increased the likelihood of achieving a ≥ 50% reduction at all monthly assessment points tested in 2 pivotal trials in episodic migraine (EM) and chronic migraine (CM). Early efficacy of migraine preventive medications is an important treatment characteristic to patients. Delays in achievement of efficacy can result in failed adherence. The objective of these post-hoc analyses were to evaluate efficacy in the first 4 weeks after initial subcutaneous administration of erenumab 70 mg, erenumab 140 mg, or placebo.MethodsThere is no generally accepted methodology to measure onset of action for migraine preventive medications. We used a comprehensive approach with data from both studies to evaluate change from baseline in weekly migraine days (WMD), achievement of ≥ 50% reduction in WMD, and proportion of patients experiencing migraine measured on a daily basis. The 7-day moving averages were overlaid with observed data.ResultsIn both studies (EM: N = 955; CM: N = 667), there was evidence of onset of efficacy of erenumab vs. placebo during the first week of treatment, which in some cases reached nominal significance. For EM the changes in WMD were (least squares mean [LSM] [95% CI]): placebo, − 0.1 (− 0.3, 0.0); erenumab 70 mg, − 0.3 (− 0.5, − 0.2) p = 0.130; erenumab 140 mg, − 0.6 (− 0.7, − 0.4) p < 0.001. For CM the changes were: placebo, − 0.5 (− 0.8, − 0.3); erenumab 70 mg, − 0.9 (− 1.2, − 0.7) p = 0.047; erenumab 140 mg, − 0.8 (− 1.1, − 0.5) p = 0.18. Achievement of ≥ 50% reduction in WMD was observed as early as Week 1 (adjusted OR [95% CI] erenumab vs placebo) in EM: erenumab 70 mg, 1.3 (1.0, 1.9) p = 0.097; erenumab 140 mg, 2.0 (1.4, 2.7) p < 0.001. A similar outcome was observed for CM: erenumab 70 mg, 1.8 (1.1, 2.8) p = 0.011; erenumab 140 mg, 1.9 (1.2, 2.9) p = 0.009. Seven-day moving averages of observed data showed each treatment arm differed from placebo by Week 1 (OR [95% CI]): in EM Day 3 for erenumab 140 mg, 0.7 (0.5, 1.0) p = 0.031 and at Day 7 for 70 mg, 0.6 (0.4, 0.8) p = 0.002; in CM: Day 6 for erenumab 70 mg, 0.6 (0.4, 0.9) p = 0.022 and at Day 7 for 140 mg, 0.7 (0.4, 1.0); p = 0.038.ConclusionErenumab showed early onset of efficacy with separation from placebo within the first week of treatment in both chronic and episodic migraine patients.

Effects of Anti-Calcitonin Gene-Related Peptide for Migraines: A Systematic Review with Meta-Analysis of Randomized Clinical Trials

“…Finally, the eligible studies were checked for data sources and they were found to be from 16 RCTs. These trials were included in this study for qualitative and quantitative synthesis [39,40,41,42,43,44,45,46,47,48,49,50,52,53,54,55,56,57,58,59,60,61,62,63,64]. The flow diagram of evidence selection is presented in Figure 1.…”

“…Secondary endpoints included the usage times of migraine-specific medication, cumulative hours of headache, Headache Impact Test 6 (HIT-6) score, and Migraine Specific Quality of Life Questionnaire (MSQ) score. All the trials indicated better outcomes and prevention of migraine with anti-CGRP medication, but the efficacy seemed to be diversified by the different interval and period of drug administration [39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64]. Though the synthesized evidences consistently confirmed that anti-CGRP had no serious adverse events reported and the effects of anti-CGRP remain controversial due to differences in follow-up and the percentage of response rate [65,66,67,68,69].…”

A Randomized Phase 2 Study of Erenumab for the Prevention of Episodic Migraine in Japanese Adults

“…Consistent with findings from previous global studies of episodic and chronic migraine, 19 responses to erenumab in the Japan study were The analysis included randomized patients who received ≥1 dose of investigational product and had ≥1 postbaseline measurement during the double-blind treatment phase. Consistent with findings from previous global studies of episodic and chronic migraine, 19 responses to erenumab in the Japan study were The analysis included randomized patients who received ≥1 dose of investigational product and had ≥1 postbaseline measurement during the double-blind treatment phase.…”

“…In this population of Japanese patients with episodic migraine, preventive treatment with erenumab 70 and 140 mg led to statistically significant improvements in each of the efficacy endpoints -change from baseline in MMD and MSMD as well as achievement of ≥50% response. Consistent with findings from previous global studies of episodic and chronic migraine, 19 responses to erenumab in the Japan study were The analysis included randomized patients who received ≥1 dose of investigational product and had ≥1 postbaseline measurement during the double-blind treatment phase. The adjusted analysis utilized a generalized linear mixed model, which included treatment, visit, treatment by visit interaction, stratification factor (previous/current treatment with migraine-preventive medication), and baseline value as covariates and assumed a first-order autoregressive covariance structure.…”

Antibodies against CGRP for prevention of migraine

“…22 A pooled analysis of these trials suggested that the benefit of erenumab was evident within the first week of treatment in chronic and episodic migraine. 23 These findings are supported by the ARISE study, which showed that erenumab 70mg weekly reduced monthly migraine days by 2.9 compared with 1.8 with placebo after 12 weeks' treatment (p<0.001). 24 Of patients treated with erenumab, 40% experienced a ≥50% reduction in migraine frequency (versus 30% with placebo, p=0.010).…”