Efficacy and Safety of Combination Pharmacotherapy for Patients with Overactive Bladder: A Rapid Evidence Assessment.

CONTEXT

Oral pharmacotherapy consisting of antimuscarinics, β3-adrenoreceptor agonists, or combinations of these agents forms the mainstay of overactive bladder (OAB) management.

OBJECTIVE

To evaluate the efficacy and safety of combination therapy in patients with OAB.

EVIDENCE ACQUISITION

A literature search was conducted in June 2018 using Embase, MEDLINE, and Cochrane databases via Ovid and relevant congress abstracts. Studies reporting the efficacy/safety of two antimuscarinics or a β3-adrenoreceptor agonist plus an antimuscarinic were included.

EVIDENCE SYNTHESIS

Publications reported on clinical efficacy, safety, and health-related quality of life (HRQoL) for mirabegron (M) plus solifenacin (S) from three 12-wk randomised controlled trials (RCTs)-SYMPHONY, SYNERGY, and BESIDE-and a 12-mo RCT, SYNERGY II. SYMPHONY reported statistically significant improvements in clinical symptoms and HRQoL with combination therapy versus solifenacin 5 mg (S5) and placebo. In SYNERGY, there were consistent improvements in urinary incontinence (UI) episodes/24 h and micturitions/24 h (coprimary endpoints), and in secondary efficacy parameters with mirabegron 25 mg (M25) + S5 and mirabegron 50 mg (M50) + S5 versus respective monotherapies. In patients with an inadequate response to S5 monotherapy (BESIDE), greater improvements in UI (primary endpoint) were noted for M50 + S5 versus S5 (p = 0.001). Combination therapy was noninferior to solifenacin 10 mg (S10) for reduction in UI and superior to S10 for improvement in micturition frequency (p < 0.001), and resulted in greater improvements from baseline in OAB-5 Dimension scores versus S5 and S10 (p < 0.01). In SYNERGY II, clinically meaningful and sustained improvements in clinical outcomes were observed for M50 + S5 versus M50 or S5. Combination therapy was well tolerated in all four trials. The incidence of adverse events (AEs) was similar across groups, and there were no notable differences in the incidence of specific AEs. Positive efficacy outcomes were observed in five studies of dual antimuscarinic therapy (trospium + solifenacin).

CONCLUSIONS

Mirabegron plus solifenacin provides effective, well-tolerated treatment for patients with OAB. Limited data for dual antimuscarinic therapy suggest a benefit in patients with moderate-to-severe symptoms.

PATIENT SUMMARY

Overactive bladder (OAB) is treated with medicines called antimuscarinics, such as solifenacin, propiverine, or trospium, or another β-adrenoreceptor agonist medicine called mirabegron, which works in a different way. We looked at published scientific studies of patients with OAB treated with mirabegron plus solifenacin together, or with two antimuscarinics. We found that mirabegron plus solifenacin can help reduce symptoms and improve quality of life. Patients tolerate this treatment well, with few patients experiencing side effects.