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(2017)Objective
Erenumab - To assess the efficacy and safety of erenumab, a CGRP receptor antibody, in preventing episodic migraine.
Study Summary
• Both 70 mg and 140 mg doses improved physical function and daily activity scores.
• Well tolerated, with adverse event rates similar to placebo.
Intervention
Phase 3, randomized, double-blind, placebo-controlled trial. 955 patients with 4–14 migraine days/month were assigned to monthly subcutaneous erenumab 70 mg, 140 mg, or placebo for 6 months. Primary endpoint was change in monthly migraine days; secondary endpoints included ≥50% responder rate, use of acute migraine medication, and Migraine Physical Function Impact Diary scores.
Inclusion Criteria
Adults aged 18–65 with episodic migraine (4–14 migraine days/month), with or without aura, and ≤2 prior preventive treatment failures.
Study Design
Arms: Erenumab 70 mg, Erenumab 140 mg, Placebo
Patients per Arm: 317 (70 mg), 319 (140 mg), 319 (placebo)
Outcome
• ≥50% reduction in migraine days: 43.3% (70 mg), 50.0% (140 mg), vs. 26.6% (placebo); ORs: 2.13 & 2.81
• Acute migraine medication use: −1.1 (70 mg), −1.6 (140 mg), vs. −0.2 (placebo); P<0.001
• MPFID Everyday Activities: −5.5 (70 mg), −5.9 (140 mg), vs. −3.3 (placebo); P<0.001
• MPFID Physical Impairment: −4.2 (70 mg), −4.8 (140 mg), vs. −2.4 (placebo); P<0.001
• Adverse events similar across groups; injection-site pain slightly more common with 70 mg.
Bottom Line
Erenumab administered subcutaneously at a monthly dose of 70 mg or 140 mg significantly reduced migraine frequency, the effects of migraines on daily activities, and the use of acute migraine-specific medication over 6 months with a safety profile similar to placebo
Major Points
- First phase 3 trial of CGRP pathway-targeted therapy for episodic migraine prevention
- 955 patients randomized 1:1:1 to erenumab 70 mg, 140 mg, or placebo for 6 months
- Mean migraine days reduced by 3.2 days (70 mg) and 3.7 days (140 mg) vs 1.8 days placebo
- 50% responder rates: 43.3% (70 mg), 50.0% (140 mg) vs 26.6% placebo
- Significant reductions in acute medication use and improvements in physical functioning
- Rapid onset of effect from month 1
- Safety profile similar to placebo with no cardiovascular safety signals
Study Design
- Study Type
- Randomized controlled trial
- Randomization
- Yes
- Blinding
- Double-blind, placebo-controlled with patients, site personnel, and sponsor personnel masked to treatment assignment
- Sample Size
- 955
- Follow-up
- 6 months (double-blind treatment phase reported)
- Centers
- 121
- Countries
- United States, Canada, Multiple European countries, Turkey
Primary Outcome
Definition: Change from baseline to months 4-6 in mean number of migraine days per month
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| -1.8 days | 70 mg: -3.2 days; 140 mg: -3.7 days | - (70 mg: -1.9 to -0.9; 140 mg: -2.3 to -1.4) | <0.001 for both doses |
Limitations & Criticisms
- Exclusion of patients with no response to >2 migraine-preventive drug classes limits generalizability
- Long-term safety and durability of effect require further study
- 6-month follow-up relatively short for chronic preventive therapy
- No direct comparison with existing oral migraine-preventive treatments
- Industry-sponsored trial with authors having financial relationships with sponsor
- Medical writer funded by Amgen wrote first draft
Citation
N Engl J Med 2017;377:2123-32