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

BMC Urology

Research Article

Caroline Dorrepaal¹  Marianne Wooning²  Nancy E Martin³  Mary Beth Blauwet⁴  Javier C Angulo⁵  Javier Cambronero⁶  Vik Khullar⁷ 

[1] Astellas Pharma Global Development – EU, Global Medical Science – Urology, Leiden, The Netherlands;Astellas Pharma Global Development, Global Clinical Science, Leiden, The Netherlands;Astellas Pharma Global Development, Global Medical Sciences, Northbrook, IL, USA;Astellas Pharma Global Development, Inc., Biostatistics, NorthbrookIL, USA;Hospital Universitario De Getafe, Department of Urology, Madrid, Spain;Infanta Leonor Hospital, Department of Urology, Madrid, Spain;Urogynaecology Department, St Mary’s Hospital, Imperial College, London, UK;

关键词: β-adrenoceptor agonist;    Mirabegron;    OAB;    Overactive bladder;    Post hoc analysis;   

DOI  :  10.1186/1471-2490-13-45

 received in 2013-06-14, accepted in 2013-09-09,  发布年份 2013

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Khullar et al.; licensee BioMed Central Ltd. 2013