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STRIVE

Study to Evaluate the Efficacy and Safety of Erenumab in Migraine Prevention

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Year of Publication: 2017

Authors: Peter J. Goadsby, Uwe Reuter, Yngve Hallström, ..., Robert A. Lenz

Journal: New England Journal of Medicine

Citation: N Engl J Med 2017;377:2123-32

PDF: https://www.nejm.org/doi/pdf/10.1056/NEJMoa1705848

Clinical Question

Does erenumab, a fully human monoclonal antibody that inhibits the CGRP receptor, effectively prevent episodic migraine when administered monthly at doses of 70 mg or 140 mg?

Study Overview

Objective

Erenumab - To assess the efficacy and safety of erenumab, a CGRP receptor antibody, in preventing episodic migraine.

Study Summary

Monthly erenumab significantly reduced migraine frequency and medication use.
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.

Patients per Arm

317 (70 mg), 319 (140 mg), 319 (placebo)

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

      

Design

Study Type: Randomized controlled trial

Randomization: 1

Blinding: Double-blind, placebo-controlled with patients, site personnel, and sponsor personnel masked to treatment assignment

Enrollment Period: July 2015 to September 5, 2016

Follow-up Duration: 6 months (double-blind treatment phase reported)

Centers: 121

Countries: United States, Canada, Multiple European countries, Turkey

Sample Size: 955

Analysis: Linear mixed-effects model without imputation for continuous endpoints; stratified Cochran-Mantel-Haenszel test for 50% responder rate; hierarchical gatekeeping procedure for multiplicity adjustment

Inclusion Criteria

Adults 18-65 years of age
History of migraine with or without aura for ≥12 months
4-14 migraine days per month on average
<15 headache days per month on average
≥80% adherence to electronic diary during baseline phase
Protocol amendment allowed inclusion of patients on one stable migraine-preventive medication

Exclusion Criteria

Age >50 years at migraine onset
History of hemiplegic migraine or cluster headache
Botulinum toxin use within 4 months before or during baseline
Use of devices or procedures for migraine prevention within 2 months before baseline
No therapeutic response to >2 migraine-preventive treatment categories

Baseline Characteristics

Characteristic	Control	Active
Mean age	41.3 years
Female sex	85.9%
Mean migraine days per month	8.2
Mean headache days per month	9.3
Mean migraine attacks per month	5.1
Days of acute medication use per month	3.4
History of preventive failure	39.8%
Current preventive medication use	3.1%
70 mg - Mean age		41.1 years
70 mg - Female sex		84.5%
70 mg - Mean migraine days per month		8.3
140 mg - Mean age		40.4 years
140 mg - Female sex		85.3%
140 mg - Mean migraine days per month		8.3
140 mg - Mean headache days per month		9.3

Arms

Field	Erenumab 70 mg	Erenumab 140 mg	Control
Intervention	Monthly subcutaneous injection of 70 mg erenumab at day 1 and weeks 4, 8, 12, 16, and 20	Monthly subcutaneous injection of 140 mg erenumab at day 1 and weeks 4, 8, 12, 16, and 20	Monthly subcutaneous injection of placebo at day 1 and weeks 4, 8, 12, 16, and 20
Duration	6 months	6 months	6 months

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Change from baseline to months 4-6 in mean number of migraine days per month	Primary	-1.8 days	70 mg: -3.2 days; 140 mg: -3.7 days		<0.001 for both doses
≥50% reduction in mean migraine days per month	Secondary	26.6%	70 mg: 43.3%; 140 mg: 50.0%	70 mg: 2.13 (1.52-2.98); 140 mg: 2.81 (2.01-3.94)	<0.001 for both doses
Change in days of acute migraine-specific medication use per month	Secondary	-0.2 days	70 mg: -1.1 days; 140 mg: -1.6 days	70 mg difference: -0.9 (-1.2 to -0.6); 140 mg: -1.4 (-1.7 to -1.1)	<0.001 for both doses
Change in MPFID everyday-activities score	Secondary	-3.3 points	70 mg: -5.5 points; 140 mg: -5.9 points	70 mg difference: -2.2 (-3.3 to -1.2); 140 mg: -2.6 (-3.6 to -1.5)	<0.001 for both doses
Change in MPFID physical-impairment score	Secondary	-2.4 points	70 mg: -4.2 points; 140 mg: -4.8 points	70 mg difference: -1.9 (-3.0 to -0.8); 140 mg: -2.4 (-3.5 to -1.4)	<0.001 for both doses
Any adverse event	Adverse	201 (63.0%)	70 mg: 180 (57.3%); 140 mg: 177 (55.5%)
Injection-site pain	Adverse	1 (0.3%)	70 mg: 10 (3.2%); 140 mg: 1 (0.3%)
Serious adverse events	Adverse	7 (2.2%)	70 mg: 8 (2.5%); 140 mg: 6 (1.9%)
Discontinuation due to AEs	Adverse	8 (2.5%)	70 mg: 7 (2.2%); 140 mg: 7 (2.2%)

Subgroup Analysis

90.4% of erenumab patients and 87.1% of placebo patients received all 6 planned doses. Anti-erenumab binding antibodies detected in 5.6% of patients (8.0% in 70 mg group, 3.2% in 140 mg group), with neutralizing antibodies in only 0.2%

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

Funding

Amgen and Novartis (co-developers of erenumab)

Based on: STRIVE (New England Journal of Medicine, 2017)