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

Todd J Schwedt, Uwe Reuter, Stewart Tepper, Messoud Ashina, David Kudrow, Gregor Broessner, Guy P. Boudreau, Peter McAllister, Thuy Vu, Feng Zhang, Sunfa Cheng, Hernan Picard, Shihua Wen, Joseph Kahn, Jan Klatt, Daniel Mikol

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Subcutaneous 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. Methods: There 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. Results: In 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. Conclusion: Erenumab showed early onset of efficacy with separation from placebo within the first week of treatment in both chronic and episodic migraine patients.

Original languageEnglish (US)
Article number92
JournalJournal of Headache and Pain
Volume19
Issue number1
DOIs
StatePublished - Oct 1 2018

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Migraine Disorders
Placebos
Therapeutics
Least-Squares Analysis

Keywords

  • Chronic migraine
  • Efficacy
  • Episodic migraine
  • Erenumab
  • Migraine preventive clinical trial
  • Migraine preventive medication
  • Onset of efficacy

ASJC Scopus subject areas

  • Clinical Neurology
  • Anesthesiology and Pain Medicine

Cite this

Early onset of efficacy with erenumab in patients with episodic and chronic migraine. / Schwedt, Todd J; Reuter, Uwe; Tepper, Stewart; Ashina, Messoud; Kudrow, David; Broessner, Gregor; Boudreau, Guy P.; McAllister, Peter; Vu, Thuy; Zhang, Feng; Cheng, Sunfa; Picard, Hernan; Wen, Shihua; Kahn, Joseph; Klatt, Jan; Mikol, Daniel.

In: Journal of Headache and Pain, Vol. 19, No. 1, 92, 01.10.2018.

Research output: Contribution to journalArticle

Schwedt, TJ, Reuter, U, Tepper, S, Ashina, M, Kudrow, D, Broessner, G, Boudreau, GP, McAllister, P, Vu, T, Zhang, F, Cheng, S, Picard, H, Wen, S, Kahn, J, Klatt, J & Mikol, D 2018, 'Early onset of efficacy with erenumab in patients with episodic and chronic migraine', Journal of Headache and Pain, vol. 19, no. 1, 92. https://doi.org/10.1186/s10194-018-0923-6
Schwedt, Todd J ; Reuter, Uwe ; Tepper, Stewart ; Ashina, Messoud ; Kudrow, David ; Broessner, Gregor ; Boudreau, Guy P. ; McAllister, Peter ; Vu, Thuy ; Zhang, Feng ; Cheng, Sunfa ; Picard, Hernan ; Wen, Shihua ; Kahn, Joseph ; Klatt, Jan ; Mikol, Daniel. / Early onset of efficacy with erenumab in patients with episodic and chronic migraine. In: Journal of Headache and Pain. 2018 ; Vol. 19, No. 1.
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TY - JOUR

T1 - Early onset of efficacy with erenumab in patients with episodic and chronic migraine

AU - Schwedt, Todd J

AU - Reuter, Uwe

AU - Tepper, Stewart

AU - Ashina, Messoud

AU - Kudrow, David

AU - Broessner, Gregor

AU - Boudreau, Guy P.

AU - McAllister, Peter

AU - Vu, Thuy

AU - Zhang, Feng

AU - Cheng, Sunfa

AU - Picard, Hernan

AU - Wen, Shihua

AU - Kahn, Joseph

AU - Klatt, Jan

AU - Mikol, Daniel

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Background: Subcutaneous 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. Methods: There 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. Results: In 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. Conclusion: Erenumab showed early onset of efficacy with separation from placebo within the first week of treatment in both chronic and episodic migraine patients.

AB - Background: Subcutaneous 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. Methods: There 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. Results: In 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. Conclusion: Erenumab showed early onset of efficacy with separation from placebo within the first week of treatment in both chronic and episodic migraine patients.

KW - Chronic migraine

KW - Efficacy

KW - Episodic migraine

KW - Erenumab

KW - Migraine preventive clinical trial

KW - Migraine preventive medication

KW - Onset of efficacy

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