An open-label prospective study of the real-life use of onabotulinumtoxinA for the treatment of chronic migraine: the REPOSE study

Abstract

Background: The PREEMPT Studies established onabotulinumtoxinA as preventive treatment for adults with chronic migraine (CM). The purpose of the REal-life use of botulinum toxin for the symptomatic treatment of adults with chronic migraine, measuring healthcare resource utilisation, and Patient-reported OutcomeS observed in practice (REPOSE) Study was to observe real-life, long-term (24-month) use of onabotulinumtoxinA in adults with CM and report on the utilisation, effectiveness, safety, and tolerability.

Methods: The REPOSE Study was a European, open-label, multicentre, prospective, noninterventional study. Patients received onabotulinumtoxinA approximately every 12 weeks according to their physician's usual practice, guided by the summary of product characteristics (SPC). Patients were observed for 24 months after initiating onabotulinumtoxinA treatment. Outcome measures were collected at baseline and all administration visits and included onabotulinumtoxinA injection practices, headache-day frequency, Migraine-Specific Quality-of-Life Questionnaire (MSQ), EuroQol 5-Dimension Questionnaire (EQ-5D), and adverse drug reactions (ADRs) to evaluate safety/tolerability.

Results: Of 641 patients enrolled, 633 received ≥1 dose of onabotulinumtoxinA for a total of 3499 treatment sessions. At baseline, mean (SD) age was 45.4 (11.7) years; patients were predominantly women (85.3%). Injection practices closely followed the SPC in mean dosage (155.1 U) and injection sites per session (31.4), with the exception of a prolongation of the recommended 12-week dosing interval, with 79.1% of patients receiving ≥1 treatment session that was > 13 weeks after the previous treatment session. Headache-day frequency was reduced from a baseline mean (SD) of 20.6 (5.4) to 7.4 (6.6) days at administration visit 8 (P < 0.001). Each MSQ domain (restrictive, preventive, and emotional) was significantly reduced from baseline through each administration visit (P < 0.001). The median EQ-5D total and health state scores were significantly improved from baseline through each administration visit (P < 0.001). Overall, 18.3% of patients reported an ADR; most were mild to moderate intensity, with only 1.3% of patients reporting a serious ADR. Eyelid ptosis (5.4%), neck pain (2.8%), and musculoskeletal stiffness (2.7%) were the most frequently reported.

Conclusions: Long-term, real-world preventive treatment of CM with onabotulinumtoxinA showed effectiveness with a sustained reduction in headache-day frequency and significant improvement in quality-of-life measures. ADRs were mild to moderate, with no new safety concerns identified.

Trial registration: Trial registration number: NCT01686581. Name of registry: ClinicalTrials.gov. URL of registry: https://clinicaltrials.gov/ct2/show/NCT01686581 . Date of retrospective registration: September 18, 2012. Date of enrolment of first patient: July 23, 2012.

Keywords: Chronic migraine; Clinical setting; Effectiveness; Long-term; OnabotulinumtoxinA; Real world; Safety.

Fig. 1

Mean change from baseline in frequency of headache days. Patient-reported estimate of number of days in a month with a headache (≥4 h) at each administration visit through visit 8.^† Mean (SD) headache-day frequency at baseline was 20.6 (5.4) days per month. *P < 0.001 Wilcoxon signed rank test for change versus baseline (level of significance: 5%). ^†The numbers of patients in administration (Admin) visits 9–13 were as follows: Admin 9, n = 119; Admin 10, n = 50; Admin 11, n = 24; Admin 12, n = 13; Admin 13, n = 7. Mean changes from baseline for Admin visits 9–13 were each significant (Admin 9–12, P < 0.001; Admin 13, P = 0.016)

Fig. 2

Mean (SD) change from baseline in all MSQ dimensions. a) Mean role-function restrictive score at baseline was 36.2 (17.8); b) mean role-function preventive score at baseline was 50.2 (22.8); c) mean role-function emotional score at baseline was 42.4 (25.6; P < 0.001). All dimensions evaluated at administration visit 2 through administration visit 8.^† MSQ = Migraine-Specific Quality-of-Life Questionnaire. *P < 0.001 Wilcoxon signed rank test for change versus baseline (level of significance, 5%). ^†The numbers of patients in administration (Admin) visits 9–13 in all dimensions were as follows: Admin 9, n = 117; Admin 10, n = 50; Admin 11, n = 23; Admin 12, n = 13; Admin 13, n = 6. Mean changes from baseline for the restrictive and preventive scores Admin visits 9–13 were each significant (Admin 9–12, P < 0.001; Admin 13, P = 0.031). Mean changes from baseline for the emotional score Admin visits 9–13 were each significant (Admin 9–11, P < 0.001; Admin 12, P = 0.010; Admin 13, P = 0.031)

Fig. 3

Change from baseline in proportion of patients per level of perceived problems in EQ-5D dimensions. a) Usual activities; b) pain/discomfort; c) anxiety/depression; d) mobility; and e) self-care. All dimensions evaluated at administration visit 1 through visit 8.* EQ-5D = EuroQol 5-Dimension Questionnaire. *The numbers of patients in administration (Admin) visits 9–13 in all dimensions were as follows: Admin 9, n = 119; Admin 10, n = 50; Admin 11, n = 24; Admin 12, n = 13; Admin 13, n = 7

Fig. 4

Median change from baseline in EQ-5D total and health state score. a) Median EQ-5D total score at baseline was 0.69; b) Median EQ-5D health state score at baseline was 50.0. Both scores were evaluated at administration visit 2 through administration visit 8.^† EQ-5D = EuroQol 5-Dimension Questionnaire. *P < 0.001 Wilcoxon signed rank test for change versus baseline (level of significance, 5%). ^†The numbers of patients in administration (Admin) visits 9–13 were as follows: Admin 9, n = 111; Admin 10, n = 47; Admin 11, n = 23; Admin 12, n = 12; Admin 13, n = 6. Median changes from baseline for Admin visits 9–13 were each significant for the total score (Admin 9–11, P < 0.001; Admin 12, P = 0.006; Admin 13, P = 0.031) and the health state score (Admin 9–11, P < 0.001; Admin 12, P = 0.002; Admin 13, P = 0.031)