Newer overactive bladder agent viable alternative to antimuscarinics

April 23, 2013

Data from a recent multicenter study provide new evidence that the beta-3 adrenoceptor agonist mirabegron (Myrbetriq) appears to be a viable alternative in patients with overactive bladder who are poor responders to antimuscarinic agents or intolerant of their adverse events.

Milan, Italy-Data from a recent multicenter study provide new evidence that the beta-3 adrenoceptor agonist mirabegron (Myrbetriq) appears to be a viable alternative in patients with overactive bladder (OAB) who are poor responders to antimuscarinic agents or intolerant of their adverse events.

“Some patients have a suboptimal response to antimuscarinic therapy or experience bothersome adverse events, such as dry mouth, constipation, or blurred vision that often lead to the discontinuation of treatment. At all doses, mirabegron revealed a very low incidence of typical antimuscarinic side effects and a statistically significant benefit for OAB symptoms over placebo,” said first author Victor Nitti MD, professor of urology and obstetrics/gynecology and vice chairman of urology at New York University Langone Medical Center, New York.

“These data suggest that mirabegron can be efficacious in subjects with overactive bladder, particularly in those experiencing intolerable dry mouth,” said Dr. Nitti, who presented the findings at the European Association of Urology annual congress in Milan, Italy.

In a pooled analysis of three phase III randomized, double-blind, placebo-controlled, 12-week studies, which assessed three doses of mirabegron (25 mg, 50 mg, and 100 mg) in patients with OAB, Dr. Nitti reviewed the incidence of adverse events commonly associated with the use of antimuscarinics. One study arm used tolterodine extended release (Detrol LA), 4 mg, as an active control. All three studies had exactly the same methodology and inclusion and exclusion criteria.

The studies enrolled 4,611 male and female patients aged ≥18 years with OAB symptoms, such as urinary frequency and urgency, with and without urgency incontinence, for ≥3 months. Following a 2-week, single-blind, placebo run-in period, patients were randomized if, during a 3-day micturition diary period, they recorded ≥8 micturitions/24 hours and three or more urgency episodes (grade 3 or 4 on the Patient Perception of Intensity and Urgency Scale).

The patients received mirabegron, 25 mg (432 patients); mirabegron, 50 mg (1,375 patients); mirabegron, 100 mg (929); tolterodine, 4 mg (495); and placebo (1,380). Adverse events that began or worsened after the first dose of the study drug until 30 days after the last dose were recorded.

 

Dry mouth incidence 5x lower

The incidence of common antimuscarinic-associated adverse events was generally low across the treatment groups. However, incidence of dry mouth was five times higher in the tolterodine treatment group (50/495 patients; 10.1%) versus the mirabegron group (54/2,736 patients; 2.0%) and the placebo group (29/1,380 patients; 2.1%). There was no increase in side effects with increasing mirabegron dosage, and there was no significant difference between doses.

Pruritus had a fivefold higher occurrence rate in the tolterodine group (7/495 patients; 1.4%) versus the mirabegron group (7/2,736 patients; 0.3%) and the placebo group (5/1,380 patients; 0.4%). Incidences of dry mouth and pruritus in the mirabegron groups were similar to that in the placebo group. Urinary retention was higher in both the tolterodine group (3/495 patients; 0.6%) and placebo group (6/1,380 patients; 0.4%) compared with mirabegron-treated patients (1/2,736 patients; <0.1%).

The incidence of dry mouth and pruritus for tolterodine in this trial (10.1% and 1.4%, respectively) was markedly lower than the incidence reported in the meta-analysis (29.6% and 15.4%, respectively).

“This study emphasizes that dry mouth, one of the most common reasons for withdrawal from antimuscarinic therapy, is not a problem with this particular compound. Mirabegron acts by binding to beta-3 adrenoceptors, which are mostly found in the detrusor muscle, by enhancing the storage function and relaxing the urinary bladder, thereby improving the symptoms associated with OAB,” Dr. Nitti said.

Dr. Nitti is a consultant and investigator for Astellas.UT