Phosphodiesterase type 5 inhibitors (PDE5-Is) are used as first-line treatment for benign prostatic hyperplasia (BPH). Because it is sometimes difficult to improve storage symptoms with a PDE5-I alone, we sought to identify further treatment strategies for these patients, including combination treatment with other agents, such as anticholinergics. The combination treatment of BPH with PDE5-Is and β3-adrenoreceptor agonists has not been extensively studied. Therefore, we conducted a study to evaluate the efficacy and safety of an add-on treatment with the β3-adrenoreceptor agonist, mirabegron, in BPH patients with persistent storage symptoms despite PDE5-I tadalafil treatment.
This was a prospective, multicentre, open-labelled study conducted at 12 sites in accordance with a protocol approved by the institutional ethics committee for clinical trials. The registration for this study started in August 2016 and ended in April 2019; patients meeting the following criteria were included: aged ≥50 years, diagnosed with BPH, and having symptoms of overactive bladder (OAB) with urinary urgency. Tadalafil (5 mg once daily) was administered orally to the patients for 4 weeks and its effect was evaluated. The treatment was deemed ineffective in patients when the OABSS question 3 score was ≥2 points and the total OABSS was ≥3 points after 4-weeks of treatment. The patients in whom tadalafil was effective received 5 mg tadalafil (once daily orally) for a further 4 weeks (the monotreatment group) and those in whom it was ineffective received 5 mg tadalafil as well as 50 mg mirabegron (once daily orally) for a further 4 weeks (the combination group).
In the 61 patients enrolled in the two groups (18 in the monotreatment group and 43 in the combination group), significant improvements from the baseline were seen at week 8 in the OABSS total score, IPSS total score, IPSS voiding score, IPSS storage score, OAB-q total score, N-QOL total score, and N-QOL bother/concern subscale score. At week 8, the range of mean changes from the baseline in the two groups were as follows: -1.8 to -2.3 for the OABSS total score, -3.0 to -4.6 for the IPSS total score, -1.2 to -1.4 for the IPSS voiding score, -1.4 to -3.5 for the IPSS storage score, and -12.6 to -14.7 for the OAB-q total score. Adverse events were reported in three patients in the monotreatment group and one patient in the combination group. No cases of urinary retention or serious AEs were reported in the two groups.
Combination treatment with tadalafil and mirabegron is effective and safe in BPH patients with persistent storage symptoms after tadalafil monotreatment.