COMPEL
(2018)Objective
To evaluate the long-term efficacy, safety, and tolerability of onabotulinumtoxinA for the prevention of headache in adults with chronic migraine when administered every 12 weeks for 9 treatment cycles (2 years) using the fixed-site, fixed-dose injection paradigm, extending beyond the previously established 56-week data.
Study Summary
• HIT-6 disability score improved by −7.1 points at week 108 (P<0.0001), and the proportion of patients with a ≥50% reduction in headache days rose from 39.5% at week 24 to 61.1% at week 108.
• Moderate or severe headache days fell by −9.5 days at week 108 (P<0.0001).
• Treatment was well tolerated: 18.3% (131/716) had ≥1 treatment-emergent adverse event (most commonly neck pain, 4.1%), only 1 serious treatment-related AE (rash), and no deaths; 52.1% (373/716) completed the full 2-year course.
Intervention
OnabotulinumtoxinA 155 U every 12 weeks via the FDA-approved fixed-site, fixed-dose paradigm (31 sites across 7 head/neck muscle areas) for 9 treatment cycles over 108 weeks.
Inclusion Criteria
Adults ≥18 years with chronic migraine (headaches on ≥15 days/month lasting ≥4 h/day), able to follow study instructions and attend visits, with stable comorbidities; one stable oral preventive medication permitted.
Study Design
Arms: OnabotulinumtoxinA 155 U every 12 weeks, fixed-site/fixed-dose, for 9 cycles (single-arm, open-label) (N=716)
Patients per Arm: OnabotulinumtoxinA: N=716 (safety); N=715 (intention-to-treat)
Outcome
• Secondary: headache days reduced by 9.2 at week 60 (P<0.0001); HIT-6 total score improved by 7.1 points at week 108 (P<0.0001).
• Moderate/severe headache days reduced by 9.5 at week 108 (P<0.0001); ≥50% headache-day responders increased to 61.1% by week 108.
Bottom Line
In a 2-year open-label study, onabotulinumtoxinA 155 U given every 12 weeks via the fixed-site, fixed-dose paradigm produced sustained, statistically significant reductions in headache days (−10.7 days at week 108) and headache-related disability (HIT-6 −7.1) in adults with chronic migraine, with a favorable long-term safety profile (18.3% treatment-emergent AEs, no deaths), supporting its consistent efficacy and tolerability beyond one year of treatment.
Major Points
- Headache day frequency was significantly reduced from a baseline of 22.0/28 days, by 9.2 days at week 60 and 10.7 days at week 108 (both P<0.0001); significant reductions began at the first assessment (week 24, −7.4 days).
- HIT-6 total disability scores improved significantly from week 12 onward (−4.4 points) and reached −7.1 points at week 108 (P<0.0001).
- Moderate or severe headache days were reduced by 6.5 at week 24, 8.1 at week 60, and 9.5 at week 108 (all P<0.0001).
- The proportion of patients achieving a ≥50% reduction in headache days increased over time from 39.5% (week 24) to 61.1% (week 108).
- Treatment was well tolerated: 131/716 patients (18.3%) reported ≥1 treatment-emergent AE (most commonly neck pain, 4.1%), only 1 serious treatment-related AE (rash), and no deaths.
- Efficacy was generally consistent across subgroups; patients already on oral preventive treatment at baseline had a slightly smaller headache-day reduction than those not on preventives (−10.2 vs −11.2 days; P=0.029).
- 52.1% (373/716) completed all 9 treatments and the 2-year study.
Study Design
- Study Type
- International, multicenter, open-label, long-term prospective study (single-arm)
- Randomization
- No
- Blinding
- Open-label (no blinding)
- Sample Size
- 716
- Follow-up
- 112 weeks total (4-week baseline + 108-week open-label treatment; 9 treatment cycles every 12 weeks)
- Centers
- 35
- Countries
- United States, Australia, South Korea
Primary Outcome
Definition: Reduction in number of headache days per 28-day period (headache frequency) immediately before week 108, based on daily diaries (IVRS)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Not applicable (single-arm; baseline 22.0 [4.8] headache days/28 d) | 11.3 (7.4) headache days/28 d at week 108 (reduction of 10.7 days from baseline) | - | <0.0001 |
Limitations & Criticisms
- Open-label, single-arm design with no placebo or active comparator limits causal inference about long-term efficacy.
- High attrition: only 52.1% completed the study, raising potential for selection/survivor bias despite mLOCF imputation.
- Patients excluded if they had previously received onabotulinumtoxinA, limiting generalizability to treatment-naive patients.
- Reliance on modified last observation carried forward (mLOCF) imputation for substantial missing diary data.
Citation
Blumenfeld AM, Stark RJ, Freeman MC, Orejudos A, Manack Adams A. Long-term study of the efficacy and safety of OnabotulinumtoxinA for the prevention of chronic migraine: COMPEL study. The Journal of Headache and Pain. 2018;19:13.