Efficacy and Safety of Mirabegron Plus Solifenacin Combination Therapy in Comparison with Solifenacin Monotherapy in Overactive Bladder: A Systematic Review and Meta-analysis

Background and Objective: Overactive bladder (OAB) is one of the most frequent reason for lower urinary tract symptoms (LUTS) in both genders, and is associated with significant impact on quality of life. Antimuscarinic agents represent the cornerstone of pharmacological management of OAB but persistence with treatment is limited by insufficient efficacy and undesirable side effects. Studies have shown that combination of β3-adrenoceptor agonist, mirabegron with solifenacin can be a promising alternative for patients with severe symptoms of OAB, not responding to standard dose of solifenacin monotherapy.

The purpose of this review was to evaluate the efficacy and safety of recently approved combination therapy of mirabegron 50 mg and solifenacin 5 mg in comparison with 5 mg and 10 mg of solifenacin monotherapy in patients with OAB.

Material & Methods: An electronic database search was carried out in EBM (Evidence Based Medicine) Reviews, Cochrane Library and PubMed using keywords Mirabegron, Solifenacin, Combination, Overactive bladder based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline to include relevant randomized controlled trials (RCT)s. The meta-analysis was performed by Review Manager 5.4 (RevMan 5.4) software.

Results: Total 907 studies were identified out of which, 4 RCTs involving a total of 5339 patients were eligible for analysis. In comparison to solifenacin 5 mg monotherapy, combination therapy resulted in significantly more improvement in mean voiding volume (MVV) per micturition (MD =11.90; 95% CI: 8.44 to 15.36, P<0.00001), frequency of micturitions/24h (MD=-0.41; 95% CI: -0.58 to -0.25; P < 0.0001), number of incontinence epi­sodes/24h (MD =-1.36;95% CI: -2.99 to 0.28; P < 0.00001) and frequency of urgency episodes/24h (MD =-0.56;95% CI: -0.83 to - 0.29; P < 0.0001). Even when compared with solifenacin 10 mg monotherapy, combination therapy showed significantly greater improvement in mean voiding volume per micturition(MD =9.01; 95% CI: 3.97 to 14.05, P<0.0005), number of micturitions/24h (MD=-0.43; 95% CI: -0.69 to -0.17; P < 0.001), frequency of incontinence epi­sodes/24h (MD =-0.62;95% CI: -1.42 to 0.17; P=0.12) and frequency of urgency episodes/24h (MD =-0.41; 95% CI: -0.69 to - 0.13; P =0.004). As Compared to solifenacin 5 mg monotherapy, combination therapy was found to have overall acceptable tolerability profile in terms of treatment-emergent adverse events (TEAEs) (OR =1.13; 95% CI: O.99 to 1.28, P=0.07), dry mouth (OR =1.11; 95% CI: O.86 to 1.11, P=0.41), constipation (OR =1.65; 95% CI: 1.12 to 2.44, P=0.01), and prolongation of QTc interval (OR =1.72; 95% CI: O.32 to 9.16, P=0.53). Whereas when compared to solifenacin 10 mg monotherapy, combination therapy was found to be better tolerated for all studied safety outcomes including TEAEs (OR =0.81; 95% CI: O.66 to 0.98, P=0.07), dry mouth (OR =0.53; 95% CI: O.38 to 0.75, P=0.0003), constipation (OR =0.86; 95% CI: 0.54 to 1.38, P=0.53) and prolongation of QTc interval (OR =0.36; 95% CI: O.06 to 1.96, P=0.24).

Conclusion: Combination therapy of mirabegron 50 mg and solifenacin 5 mg leads to significantly greater improvement in OAB symptoms and is better tolerated in comparison with solifenacin 10 monotherapy. In patients refractory to solifenacin 5 mg monotherapy, combination therapy seems to be a better alternative as against escalating the dose of solifenacin.