Comparison of the effectiveness of repeated injections of onabotulinum toxin A for refractory idiopathic detrusor overactivity: analysis of an open label extension of a randomized trial (the RELAX study).

ABSTRACT

AIMS: To assess effects of repeat treatment with onabotulinumtoxin A (onaBoNT-A) in women with refractory idiopathic detrusor overactivity (DO). METHODS: Analysis of an open-label extension study of a large randomized placebo controlled trial of onaBoNT-A. Participants had been randomized to receive 200 IU onaBoNTA or placebo and were offered up to two further onaBoNTA injections over a 5-year period. For this analysis, the primary outcome was duration of treatment effect by patient-reported symptom return. Weibull proportional hazards regression models were fitted in a Bayesian framework to estimate missing times. Multivariable hazard regression analysis (hazard ratio, 95% credible intervals (HR, 95% CrI) compared repeated injections adjusting for differences in baseline symptom severity. Secondary outcomes included inter-injection interval, incontinence, urgency, and voiding episodes 6 weeks after injection. RESULTS: Four hundred and forty-two active injections were administered 228 patients had one, 155 had two, and 59 had three injections. Time to symptom return for injection number 1 and 2 was 84 (95%CI 63, 112) and 180 (95%CI 135, 223) days, respectively. Median inter-injection intervals for receiving second and third injection were 266 days (range 130, 1400) and 372 days (range 134, 1283). No statistically significant differences in symptom outcomes or time to symptom return (HR 0.88, 95% CrI 0.37, 2.07 for injection 2, HR 0.33, 95% CrI 0.09, 1.03 for injection 3) were observed. CONCLUSIONS: Repeated onaBoNT-A injections have consistent efficacy and duration of action. There appears to be long-term placebo effects in both groups of randomized patients, with implications for open-label extension studies.