PROGRESS
(2024)Objective
To evaluate the efficacy of atogepant for the preventive treatment of chronic migraine in participants with and without acute medication overuse.
Study Summary
• Atogepant 60mg QD reduced MMDs vs placebo by -1.9 days (95% CI -3.2 to -0.6) in patients with acute medication overuse
• ≥50% MMD reduction achieved by 44.7% (30mg BID, OR 2.5 [1.5-4.0]) and 41.8% (60mg QD, OR 2.3 [1.4-3.7]) vs 24.9% placebo in the overuse subgroup
• 52.1%-61.9% reduction in proportion of atogepant-treated participants meeting acute medication overuse criteria over 12 weeks
• Similar efficacy seen in subgroup without acute medication overuse; PRO measures improved
Intervention
Atogepant 30 mg twice daily or 60 mg once daily vs placebo for 12 weeks
Inclusion Criteria
Adults 18-80 years with ≥1-year history of chronic migraine, ≥15 monthly headache days and ≥8 monthly migraine days during 4-week baseline, migraine onset before age 50
Study Design
Arms: Atogepant 30 mg BID (n=253) vs Atogepant 60 mg QD (n=256) vs Placebo (n=246)
Patients per Arm: 253 / 256 / 246 (mITT); 500/755 (66.2%) met acute medication overuse criteria
Outcome
• MHD reduction with overuse: LSMD -2.8 days (30mg BID) and -2.1 days (60mg QD) vs placebo
• Acute medication use days reduced by LSMD -2.8 (30mg BID) and -2.6 (60mg QD) days vs placebo
• ≥50% MMD reduction: OR 2.5 (30mg BID) and 2.3 (60mg QD) vs placebo in overuse subgroup
• 52.1%-61.9% of atogepant-treated participants no longer met acute medication overuse criteria
Bottom Line
Atogepant (30 mg BID or 60 mg QD) is effective for preventive treatment of chronic migraine in patients with and without acute medication overuse, reducing MMDs, MHDs, acute medication use days, and the proportion of patients meeting medication overuse criteria, with improvements in patient-reported outcomes.
Major Points
- Atogepant 30 mg BID reduced MMDs vs placebo by -2.7 days (95% CI -4.0 to -1.4) in patients with acute medication overuse
- Atogepant 60 mg QD reduced MMDs vs placebo by -1.9 days (95% CI -3.2 to -0.6) in patients with acute medication overuse
- Mean MHDs reduced by LSMD -2.8 (30mg BID) and -2.1 (60mg QD) vs placebo in overuse subgroup
- Mean acute medication use days reduced by LSMD -2.8 (30mg BID) and -2.6 (60mg QD) vs placebo in overuse subgroup
- ≥50% MMD reduction: 44.7% (30mg BID, OR 2.5) and 41.8% (60mg QD, OR 2.3) vs 24.9% placebo in overuse subgroup
- 52.1%-61.9% of atogepant-treated participants no longer met medication overuse criteria over 12 weeks
- Similar efficacy and improvements in PROs (HIT-6, MSQv2.1, AIM-D) seen in subgroup without acute medication overuse
- Class II evidence that atogepant reduces MMDs, MHDs, and acute medication use days regardless of medication overuse status
Study Design
- Study Type
- Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial (subgroup analysis)
- Randomization
- Yes
- Blinding
- Double-blind
- Sample Size
- 778
- Follow-up
- 12-week double-blind treatment period plus 4-week follow-up
- Centers
- 142
- Countries
- Multiple - North America, Europe, East Asia
Primary Outcome
Definition: Change from baseline in mean monthly migraine days (MMDs) across the 12-week treatment period (subgroup analysis by acute medication overuse status)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Placebo (acute medication overuse subgroup) | Atogepant 30 mg BID and 60 mg QD | - (30 mg BID with overuse: -4.0 to -1.4; 60 mg QD with overuse: -3.2 to -0.6; 30 mg BID without overuse: -3.5 to 0.2; 60 mg QD without overuse: -3.5 to 0.3) |
Limitations & Criticisms
- Subgroup analyses other than primary/secondary endpoints were not controlled for type I error
- Analyses not powered to compare the two atogepant dosing regimens directly
- 12-week treatment duration limits assessment of longer-term efficacy and safety
- Industry-sponsored trial (AbbVie) with multiple authors employed by sponsor
- Class II evidence (not Class I) per AAN classification
Citation
Neurology 2024;103:e209584