title: Efficacy of the β3-adrenoceptor agonist mirabegron for the treatment of overactive bladder by severity of incontinence at baseline: a post hoc analysis of pooled data from three randomised phase 3 trials.
abstract: The β3-adrenoceptor agonist mirabegron is approved for treatment of the symptoms of overactive bladder (OAB). Incontinence can be the most bothersome of OAB symptoms. Hence, we conducted a post hoc analysis of pooled data from three randomised, double-blind, placebo-controlled, 12-wk, phase 3 studies of mirabegron to evaluate the efficacy of mirabegron 50mg in incontinent OAB patients and in subgroups of patients stratified by severity of incontinence at baseline (an average of two or more [FAS-I ≥ 2 subgroup] or four or more [FAS-I ≥ 4 subgroup] incontinence episodes per 24h at baseline, where FAS-I is the full analysis set-incontinence population) and to determine correlations between measures of efficacy and disease severity. Mirabegron 50mg resulted in statistically significant improvements from baseline to final visit versus placebo in mean number of incontinence episodes, micturitions, and urgency episodes per 24h and mean volume voided per micturition in the pooled incontinent population and in the FAS-I ≥ 2 and FAS-I ≥ 4 subgroups. Treatment effect versus placebo for incontinence and urgency episodes increased with increasing severity of incontinence at baseline. Moderate correlations were seen between improvement in both frequency of incontinence episodes and micturitions and baseline incontinence and micturition frequency, respectively, with mirabegron 50mg and placebo.
  
  
  RESULTS
  Incontinence can be the most bothersome of OAB symptoms; mirabegron 50mg once daily is effective for treatment of OAB symptoms in incontinent patients, and its effect increases with increasing severity of incontinence.
authors.affiliation: Department of Urology, Royal Hallamshire Hospital, Sheffield, UK. Electronic address: c.r.chapple@shef.ac.uk.
authors.forename: Christopher
authors.initials: C
authors.lastname: Chapple
authors.affiliation: St Mary's Hospital, Imperial College, Urogynaecology Department, London, UK.
authors.forename: Vik
authors.initials: V
authors.lastname: Khullar
authors.affiliation: NYU Langone Medical Center, New York, NY, USA.
authors.forename: Victor W
authors.initials: VW
authors.lastname: Nitti
authors.affiliation: Seattle Urology Research Center, Seattle, WA, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Frankel
authors.affiliation: Department of Surgery/Urology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sender
authors.initials: S
authors.lastname: Herschorn
authors.affiliation: Department of Biostatistics, Astellas Pharma Global Development, Leiden, The Netherlands.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Kaper
authors.affiliation: Department of Biostatistics, Astellas Pharma Global Development, Northbrook, IL, USA.
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Blauwet
authors.affiliation: Astellas Pharma Europe Ltd, Chertsey, Surrey.
authors.forename: Emad
authors.initials: E
authors.lastname: Siddiqui
mesh_terms: D000083:Acetanilides / Q000627:therapeutic use*; D058667:Adrenergic beta-3 Receptor Agonists / Q000627:therapeutic use*; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013844:Thiazoles / Q000627:therapeutic use*; D053201:Urinary Bladder, Overactive / Q000150:complications / Q000188:drug therapy*; D014549:Urinary Incontinence / Q000209:etiology*; D014554:Urination
chemical_list: D000083:Acetanilides; D058667:Adrenergic beta-3 Receptor Agonists; D013844:Thiazoles; C520025:mirabegron
keywords: Correlation analysis; Efficacy; Incontinence; Mirabegron; Overactive bladder; Severity