Long‐term safety and efficacy of antimuscarinic add‐on therapy in patients with overactive bladder who had a suboptimal response to mirabegron monotherapy: A multicenter, randomized study in Japan (MILAI II study)

OBJECTIVES: To evaluate the long‐term safety (primary objective) and efficacy (secondary objective) of antimuscarinic add‐on therapy in patients receiving mirabegron. METHODS: During a 2‐week screening period, patients (aged ≥20 years, mirabegron treatment for ≥6 weeks, residual overactive bladder symptoms) received mirabegron 50 mg once daily. These patients were subsequently randomized to 52 weeks’ treatment with mirabegron 50 mg/day plus an antimuscarinic (solifenacin 5 mg, propiverine 20 mg, imidafenacin 0.2 mg, or tolterodine 4 mg) with the potential to double the antimuscarinic dose (except for tolterodine) at week 8. Safety assessments included treatment‐emergent adverse events, vital signs, 12‐lead electrocardiograms, post‐void residual volume, and laboratory evaluations. Efficacy was assessed using changes from baseline in overactive bladder symptom score total score; overactive bladder questionnaire short form score; micturitions, urgency episodes, urinary incontinence episodes, and urgency urinary incontinence episodes/24 h; mean volume voided per micturition; and number of night‐time micturitions. RESULTS: Overall, 80.2% of patients (88.1% women, mean age 65 years) experienced at least one treatment‐emergent adverse event, with similar rates for all treatments. The adverse events most commonly reported were dry mouth, nasopharyngitis, and constipation. No marked change was observed in systolic or diastolic blood pressure for any treatment, although pulse rate increased slightly in the mirabegron and propiverine, and mirabegron and tolterodine groups. For all treatments, significant improvements were observed in all efficacy parameters, including overactive bladder symptom score total and questionnaire short form scores. CONCLUSIONS: Antimuscarinic add‐on therapy is well tolerated and effective after initial treatment with mirabegron in patients with overactive bladder symptoms.