Long-term study of the efficacy and safety of OnabotulinumtoxinA for the prevention of chronic migraine: COMPEL study

Abstract

Background: OnabotulinumtoxinA is approved for the prevention of headache in those with chronic migraine (CM); however, more clinical data on the risk-benefit profile for treatment beyond one year is desirable.

Methods: The Chronic Migraine OnabotulinuMtoxinA Prolonged Efficacy open Label (COMPEL) Study ( ClinicalTrials.gov , NCT01516892) is an international, multicenter, open-label long-term prospective study. Adults with CM received 155 U of onabotulinumtoxinA (31 sites in a fixed-site, fixed-dose paradigm across 7 head/neck muscles) every 12 weeks (±7 days) for 9 treatment cycles (108 weeks). The primary outcome was headache day reductions at 108 weeks; secondary outcomes were headache day reductions at 60 weeks and change in the 6-item Headache Impact Test (HIT-6) score. Safety and tolerability were assessed by reviewing the frequency and nature of adverse events (AEs). AEs were determined at each visit through patient self-report, general non-directed and, for specific AEs, directed questioning, and physical examination. Subgroup analyses for safety and efficacy included, but were not limited to, patients with/without concomitant oral preventive treatment and acute medication overuse at baseline.

Results: Enrolled patients (N = 716) were 18-73 years old and most were female (n = 607, 84.8%). At baseline, patients reported an average 22.0 (SD = 4.8) headache days per month. 52.1% of patients (n = 373) completed the study. By 60 and 108 weeks, a significant reduction in headache days (- 9.2 days and - 10.7 days, respectively, P < 0.0001) was observed. Significant improvements (P < 0.0001) in HIT-6 scores (- 7.1 point change at week 108) were also demonstrated. 131 patients (18.3%) reported ≥1 treatment-emergent adverse events; most frequently reported was neck pain (n = 29, 4.1%). One patient reported a serious treatment-related adverse event (rash). No deaths were reported.

Conclusions: The COMPEL Study provides additional clinical evidence for the consistency of the efficacy and for the long-term safety and tolerability of onabotulinumtoxinA for the prevention of headache in those with CM who have been treated with onabotulinumtoxinA every 12 weeks over 2 years (9 treatments) with the fixed-site, fixed-dose injection paradigm.

Trial registration: Trial registration number: NCT01516892 . Name of registry: clinicaltrials.gov . Date of registration: January 20 2012. Date of enrollment of first patient: December 2011.

Keywords: Chronic migraine; Efficacy; Long-term; OnabotulinumtoxinA; Prophylaxis; Safety.

Conflict of interest statement

Ethics approval and consent to participate

The study received ethical approval from the Institutional Review Board or Independent Ethics Committee at each site, and written informed consent was obtained from patients before study enrollment.

Consent for publication

Not applicable.

Competing interests

Andrew M. Blumenfeld has served on advisory boards and/or has consulted for Allergan, Pernix, Teva, Avanir, Depomed, and Supernus, and has received funding for travel, speaking, and/or royalty payments from Allergan. Richard J. Stark has served on advisory boards and/or has consulted for Allergan, has served on advisory boards for Novartis and has received funding for travel and/or speaking payments from Allergan, MSD, AbbVie and SciGen, and from In Vivo Academy relating to a Pfizer-sponsored project. Marshall C. Freeman has served on advisory boards and/or has consulted or received research support from Alder, Allergan, Avani, Dr. Reddy’s Laboratories, Eli Lilly, Scion, and Teva. Amelia Orejudos is an employee of Allergan plc. Aubrey Manack Adams is an employee of Allergan plc and owns stock in the company.

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Figures

Fig. 1

Overview of COMPEL Study design. HIT-6 = 6-item Headache Impact Test; IVRS = interaction voice response system; PHQ-9 = 9-item Patient Health Questionnaire. Adapted from Blumenfeld AM, Aurora SK, Laranjo K, Papapetropoulos S. Unmet Clinical Needs in Chronic Migraine: Rationale for Study and Design of COMPEL, an Open-Label, Multicenter Study of the Long-Term Efficacy, Safety, and Tolerability of OnabotulinumtoxinA for Headache Prophylaxis in Adults With Chronic Migraine. BMC Neurol. 2015; 15: 1–9

Fig. 2

Patients who completed/withdrew from the study, including a summary of reasons for study withdrawal

Fig. 3

Oral preventive treatments* currently or previously used by the enrolled population (N = 716). *Oral preventive treatments defined, for the purposes of this study, as any oral medication specifically prescribed for daily use for prevention of headache. NSAID = nonsteroidal anti-inflammatory drug

Fig. 4

Long-term effect of onabotulinumtoxinA on number of and change vs baseline. a) Number of headache days and b) number of moderate or severe headache days per 28-d period preceding the visit over 108 wk. (depicting the outcomes of treatment after 9 cycles). *P < 0.0001; paired t-test used to compare visit to baseline

Fig. 5

Long-term effect of onabotulinumtoxinA by country. a) HIT-6 total score and b) change in HIT-6 total score vs baseline, depicting the outcomes after 5 (wk 60) and 9 (wk 180) treatments. HIT-6 = 6-item Headache Impact Test. *Indicates P < 0.001 vs baseline; paired t-test used to compare visit to baseline. †Indicates P = 0.0008 for comparison between subgroups; 1-way analysis of variance

Fig. 6

Long-term effect of onabotulinumtoxinA by country. a) Number of headache days per 28-d period and b) change in number of headache days vs baseline, depicting the outcomes after 5 (wk 60) and 9 (wk 180) treatments. *P < 0.001; paired t-test used to compare visit to baseline. †P-value for comparing among subgroups is from one-way analysis of variance