Efficacy of mirabegron in patients with and without prior antimuscarinic therapy for overactive bladder: a post hoc analysis of a randomized European-Australian Phase 3 trial

Abstract

BackgroundAntimuscarinic agents are currently the predominant treatment option for the clinical management of the symptoms of overactive bladder (OAB). However, low rates of persistence with these agents highlight the need for novel, effective and better-tolerated oral pharmacological agents. Mirabegron is a β3-adrenoceptor agonist developed for the treatment of OAB, with a mechanism of action distinct from that of antimuscarinics. In a randomized, double-blind, placebo- and active-controlled Phase 3 trial conducted in Europe and Australia (NCT00689104), mirabegron 50 mg and 100 mg resulted in statistically significant reductions from baseline to final visit, compared with placebo, in the co-primary end points – mean number of incontinence episodes/24 h and mean number of micturitions/24 h. We conducted a post hoc, subgroup analysis of this study in order to evaluate the efficacy of mirabegron in treatment-naïve patients and patients who had discontinued prior antimuscarinic therapy because of insufficient efficacy or poor tolerability.MethodsPatients were randomized to placebo, mirabegron 50 or 100 mg, or tolterodine extended release (ER) 4 mg orally, once-daily, for 12 weeks. For the post hoc analysis, the primary patient population was divided into the following subgroups: (1) patients who had not received any prior antimuscarinic OAB medication (treatment-naïve) and (2) patients who had received prior antimuscarinic OAB medication. The latter subgroup was further subdivided into patients who discontinued due to: (3) insufficient efficacy or (4) poor tolerability. Analysis of the co-primary efficacy endpoints by subgroup was performed using analysis of covariance with treatment group, subgroup, sex, geographical region, and subgroup-by-treatment interaction as fixed factors; and baseline value as a covariate.ResultsMirabegron, 50 mg and 100 mg once-daily, demonstrated similar improvements in the frequency of incontinence episodes and micturitions in OAB patients who were antimuscarinic-naïve and who had discontinued prior antimuscarinic therapy. While mirabegron demonstrated improvements in incontinence and micturition frequency in patients who had discontinued prior antimuscarinic therapy due to insufficient efficacy, the response to tolterodine was similar to that of placebo.ConclusionIn this post hoc subgroup analysis, mirabegron provided treatment benefits in OAB patients who were antimuscarinic treatment-naïve and in patients who had received prior antimuscarinic treatment.

Cost-effectiveness of mirabegron compared to tolterodine ER 4 mg for overactive bladder in Canada

“…30 Furthermore, in a post-hoc analysis of the SCORPIO trial, designed to evaluate efficacy in treatment-naïve patients and in those previously treated with an antimuscarinic, mirabegron demonstrated significant reductions in frequency and incontinence in both subgroups, while the response to tolterodine ER 4 mg was similar to placebo. 31 The pooled analysis also demonstrated that the tolerability profile of mirabegron was similar to that of placebo and tolterodine ER 4 mg, with the exception of dry mouth, where the incidence was five times higher with tolterodine ER 4 mg than with mirabegron. 32 In a review of clinical trials of up to 12 months, the most common adverse events (AEs) observed with mirabegron were hypertension, nasopharyngitis, and urinary tract infection.…”

“…The extent to which the results of the current analysis can be extrapolated to treatment-naïve patients is not clear. However, it is notable that in a post-hoc analysis of data from the SCORPIO study, the effect of mirabegron in treatment-naïve patients was greater than that observed with tolterodine ER 4 mg. 31 A number of other antimuscarinic agents are available in Canada for treating OAB (oxybutynin, solifenacin, trospium, and fesoterodine). The cost-effectiveness of mirabegron vs. these agents in Canada is not known.…”

“…AE data were taken from the subgroup of previously treated patients in the SCORPIO study (49.6% of the total study population) 29,31 and transition probabilities between symptom levels were obtained by applying multinomial logistic regression models to the SCORPIO data. Three transition matrices were produced for each type of symptom: one for the transition between baseline and the first month; one between the first and second months; and one between the second and third months (Supplementary Table 1; available at www.cuaj.ca).…”

“…37 Patient distribution was based on the SCORPIO study. 29,31 Patients could have differing severities for each symptom and were, therefore, described using the format (Mx, Iy); for example, a patient described as (M2, I3) has 8-10 micturitions per day and 1-2 incontinence episodes.…”

“…[40][41][42]48 Unit costs per incontin- Symptom severity cutoff points between different levels were roughly based on qui ntiles for each number in pooled data from three pivotal, randomized trials of mirabegron: SCORPIO, 29,31 ARIES, 28 and CAPRICORN. 37 Patient distribution was based on the SCORPIO study.…”