Mirabegron in combination with solifenacin significantly reduced overactive bladder (OAB) symptoms, in a small preliminary study from Japan.

A total of 223 patients (84% female), aged over 20, mean 65 years, with overactive bladder, currently being treated with either 2.5 mg or 5 mg of solifenacin, entered the treatment phase of the study. Mirabegron was given at 25 mg once daily for the first eight weeks of the 16-week open label study, and increased to 50 mg once daily if ineffective at eight weeks. Overall 130 patients increased their mirabegron dose at this time point.

Efficacy was assessed using the Overactive Bladder Symptom Score (OABSS). Overall, this score decreased significantly in patients taking combination therapy, with further improvement seen when increasing the dose of mirabegron. In all treatment groups the threshold for minimal clinically important change i.e. 3 points was exceeded (range -3.4 to -4.0).

Across all treatment groups, urinary frequency, nocturia episodes, urgency episodes and urgency incontinence episodes all decreased, see below, while the mean volume voided per micturition increased.

• Reduction in mean number of micturitions/24 hours ranged from -1.89 to -2.36

• Reduction in mean number of nocturia episodes/night ranged from -0.31 to -0.60

• Reduction in urgency episodes/24 hours ranged from -1.57 to -2.59

• Reduction in urinary incontinence episodes/24 hours ranged from -1.06 to -1.32

Overall, 23% of patients reported new side effects during the study (almost all of which were deemed mild or moderate). The most common side effect was constipation, seen in 5-9% of patients. Only one patient reported the new onset of dry mouth, and four discontinued treatment because of side effects.

This was an open label study with no placebo arm, over a relatively short time period of 16 weeks of treatment. So the results must therefore be interpreted with caution.

Mirabegron is a beta-3 adrenoceptor agonist which works by relaxing detrusor smooth muscle during bladder storage, and increasing bladder capacity, thus aiming to reduce urgency episodes and urinary frequency. It does not have the classic side effects associated with antimuscarinic therapy such as dry mouth. A technology appraisal by NICE in 2013 recommended use of mirabegron for patients where antimuscarinics are either contraindicated, not tolerated or ineffective.

Clearly, combination therapy represents a promising development in the medical treatment of the symptoms of overactive bladder. Formal, double blind, randomised controlled trials are shortly due to report and it will be interesting to see if these findings are replicated in a more rigorous trial setting.

More importantly, the results will need to be analysed to see if improvements in symptoms are clinically significant to patients in order to justify the addition of a further long-term therapy, and a significant increase in the cost of medical treatment.

Dr Jonathan Rees