Mirabegron Add-on Therapy to Tamsulosin for the Treatment of Overactive Bladder in Men with Lower Urinary Tract Symptoms: A Randomized, Placebo-controlled Study (MATCH)

Abstract

Background: Men with lower urinary tract symptoms (LUTS) treated with a-blockers (eg, tamsulosin) may experience overactive bladder (OAB) symptoms and receive add-on antimuscarinics. Mirabegron (a b3-adrenoreceptor agonist) is an alternative add-on therapy. Objective: To evaluate the efficacy of mirabegron versus placebo in men with OAB symptoms receiving tamsulosin for LUTS. Design, setting, and participants: Japanese and Korean men with OAB treated with tamsulosin for LUTS (January 2016-July 2017). Intervention: Single-blind, 4-wk screening: tamsulosin plus placebo orally once daily; double-blind, 12-wk treatment: patients randomized (n = 568) to mirabegron 50 mg or placebo, as add-on to tamsulosin. Outcome measurements and statistical analysis: Primary endpoint: baseline to end of treatment (EoT) change in the mean number of micturitions/24 h, based on a 3-d voiding diary. Secondary endpoints: change in other diary variables and patient-reported outcomes from baseline to EoT. The primary endpoint was analyzed by analysis of covariance, including treatment group and region as fixed factors and baseline as a covariate. Results and limitations: Mirabegron add-on therapy was superior to placebo in improving the primary endpoint (adjusted mean difference [95% confidence interval] vs placebo-0.52 [-0.82 to-0.21]) and secondary endpoints, including mean volume voided/micturition (12.08 [6.33-17.84]), OAB symptom score (-0.65 [-1.04 to-0.26]), International Prostate Symptom Score total (-1.19 [-1.94 to-0.44]), storage (-0.78 [-1.13 to-0.43]), quality of life scores (-0.29 [-0.51 to-0.07]), OAB symptom bother (-4.52 [-6.91 to-2.13]), and total health-related quality of life (2.79 [1.13 to 4.44]). Differences, compared with placebo, in urgency, urgency urinary incontinence, and nocturia were not statistically significant. Mirabegron was well tolerated, with no major safety concerns. Limitations included a lack of antimuscarinic comparison. Conclusions: The mirabegron add-on therapy to tamsulosin for 12 wk in men with LUTS and OAB symptoms demonstrated superior efficacy to placebo and was well tolerated. Patient summary: We looked at the efficacy and safety of mirabegron compared with placebo in men being treated with tamsulosin but who still had overactive bladder symptoms. Mirabegron improved overactive bladder symptoms and patient-reported outcomes compared with placebo, and was well tolerated.

Mirabegron Vs Placebo Add-on Therapy in Men With Overactive Bladder Symptoms Receiving Tamsulosin for Underlying Benign Prostatic Hyperplasia: A Safety Analysis From the Randomized, Phase 4 PLUS Study

“…previous studies that found the majority of TEAEs were mild or moderate following TAM + MIRA treatment. 19,23 Furthermore, similar low incidences of serious TEAEs were reported in both PLUS (2.8%) and in MATCH (2.1%) following TAM + MIRA treatment. 19 No deaths were reported in either study, which comprised 1283 randomized patients overall.…”

“…19,23 Furthermore, similar low incidences of serious TEAEs were reported in both PLUS (2.8%) and in MATCH (2.1%) following TAM + MIRA treatment. 19 No deaths were reported in either study, which comprised 1283 randomized patients overall. In PLUS, a low proportion of TAM + MIRA patients experienced a TEAE that caused the patient to discontinue from the study.…”

“…Conversely, in both the similar MATCH study involving Japanese and Korean men and the pooled analysis of male patients from 5 Phase 3 studies, similar incidences of TEAEs were reported in both the mirabegron and placebo groups. 18,19 It is interesting to note, however, that similar incidences of overall TEAEs were noted in the TAM + MIRA groups from both PLUS (25.9%) and MATCH (23.4%). 19 In our study, a higher incidence of drug-related TEAEs was reported for the TAM + MIRA group, whereas similar incidences were observed for both groups in MATCH.…”

“…18,19 It is interesting to note, however, that similar incidences of overall TEAEs were noted in the TAM + MIRA groups from both PLUS (25.9%) and MATCH (23.4%). 19 In our study, a higher incidence of drug-related TEAEs was reported for the TAM + MIRA group, whereas similar incidences were observed for both groups in MATCH. Overall, over 90% of the TEAEs reported in PLUS were mild or moderate in severity.…”

“…Regarding add-on treatment, in the MATCH study, 565 Japanese and Korean men with OAB symptoms received either mirabegron or placebo in combination with tamsulosin. 19 No unexpected safety concerns were noted in this 12-week, randomized study.…”