Erenumab CM-MO
(2019)Objective
To determine the effect of erenumab, a human anti-CGRP receptor monoclonal antibody, in patients with chronic migraine and medication overuse, as a planned subgroup analysis of a pivotal CM prevention trial.
Study Summary
• ≥50% MMD reduction achieved by 36% (70 mg, OR 2.67 [1.36–5.22]) and 35% (140 mg, OR 2.51 [1.28–4.94]) vs 18% with placebo
• Acute migraine-specific medication treatment days fell by −5.4 (70 mg) and −4.9 (140 mg) vs −2.1 days with placebo
• Erenumab improved HIT-6, MIDAS, and MSQ scores beyond minimally important differences and shifted many patients from medication-overuse to nonoveruse status
Intervention
Subcutaneous erenumab 70 mg or 140 mg monthly vs placebo for 3 months in patients with chronic migraine, with prespecified subgroup analysis by baseline medication overuse status.
Inclusion Criteria
Adults with chronic migraine (≥15 headache days/month, ≥8 migraine days/month); medication overuse subgroup defined per IHS-style criteria as ≥15 days/month simple analgesics, ≥10 days/month triptans, or ≥10 days/month combination therapy.
Study Design
Arms: Placebo (n=286) vs Erenumab 70 mg monthly SC (n=191) vs Erenumab 140 mg monthly SC (n=190); medication overuse subgroup: Placebo n=117, Erenumab 70 mg n=79, Erenumab 140 mg n=78
Patients per Arm: Medication overuse subgroup: Placebo 117, Erenumab 70 mg 79, Erenumab 140 mg 78 (Total subgroup n=274 of 667 randomized)
Outcome
• ≥50% responders (medication overuse): 36% and 35% (erenumab) vs 18% (placebo)
• Acute migraine-specific medication days: −5.4 and −4.9 vs −2.1 days; treatment differences −3.3 (70 mg) and −2.8 (140 mg)
• Transition to nonoveruse at month 3: simple analgesics 60%/71% vs 52% placebo; triptans 65%/54% vs 33% placebo; combination 45%/59% vs 40% placebo
• AE profile similar across groups; most common erenumab AEs were injection-site erythema, muscle spasms, and migraine
Bottom Line
In patients with chronic migraine and medication overuse, erenumab 70 mg or 140 mg monthly approximately doubled the chance of ≥50% migraine-day reduction at 3 months (≈35% vs 18% placebo), cut monthly migraine days by ~6.6 days vs 3.5 with placebo, and meaningfully reduced acute migraine-specific medication days while improving disability and quality-of-life measures, supporting CGRP-receptor blockade as an effective preventive option in this hard-to-treat population.
Major Points
- 274 of 667 randomized CM patients (41%) met medication overuse criteria; this subgroup had higher baseline MMD (19.0 vs 17.3) and more prior preventive failures (75% vs 63%).
- At month 3, erenumab 70 mg and 140 mg both reduced MMD by −6.6 days vs −3.5 days with placebo in the medication-overuse subgroup (treatment difference −3.1 days, 95% CI −4.8 to −1.4).
- ≥50% MMD responder rates in the medication-overuse subgroup: 36% (70 mg, OR 2.67 [1.36–5.22]) and 35% (140 mg, OR 2.51 [1.28–4.94]) vs 18% (placebo).
- Acute migraine-specific medication days fell by −5.4 (70 mg) and −4.9 (140 mg) vs −2.1 days (placebo) in the medication-overuse subgroup.
- Substantial transition from overuse to nonoveruse status at month 3 with erenumab, particularly for simple analgesics (60%/71% vs 52% placebo) and triptans (65%/54% vs 33% placebo).
- HIT-6, MIDAS, and MSQ Role Function–Restrictive and Emotional Functioning scores improved beyond minimally important differences in both subgroups.
- Effects in the medication-overuse subgroup were similar in magnitude to those in the non–medication-overuse subgroup; safety profile mirrored the parent trial.
- Class II evidence that erenumab reduces MMD at 3 months in CM with medication overuse.
Study Design
- Study Type
- Preplanned subgroup analysis of a phase 3 randomized, double-blind, placebo-controlled trial in chronic migraine
- Randomization
- Yes
- Blinding
- Double-blind (patient and investigator)
- Sample Size
- 667
- Follow-up
- 3-month double-blind treatment phase
- Centers
- 69
Primary Outcome
Definition: Change from baseline in monthly migraine days (MMD) at month 3 in patients with chronic migraine and medication overuse
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Placebo: −3.5 days (95% CI −4.6 to −2.4) | Erenumab 70 mg: −6.6 days (−8.0 to −5.3); Erenumab 140 mg: −6.6 days (−8.0 to −5.3) | - (−4.8 to −1.4 (treatment difference, medication overuse subgroup)) |
Limitations & Criticisms
- Subgroup analysis with no adjustment of p values for multiple comparisons; some analyses (PROs by overuse subgroup, overuse-by-visit) were post hoc
- Short 3-month double-blind phase limits assessment of durability and long-term safety
- Patients on opioid overuse and those on concurrent preventives were excluded, limiting generalizability to a subset of real-world refractory CM patients
- Industry-sponsored (Amgen) with multiple Amgen-employed authors
Citation
Neurology 2019;92:e2309-e2320. doi:10.1212/WNL.0000000000007497