Alicia Ault

May 29, 2015

NEW ORLEANS — For patients with overactive bladder, the addition of mirabegron (Myrbetriq, Astellas Pharma) to solifenacin (Vesicare, Astellas Pharma) appears to confer added control and benefit without any troubling adverse effects, according to results from the phase 3b BESIDE trial.

This is good news for patients who don't respond to monotherapy, said Marcus Drake, BM BCh, from the University of Bristol and the Bristol Urological Institute in the United Kingdom.

"The detrimental impact of overactive bladder is clear, especially for patients with urgency urinary incontinence," he said here at the American Urological Association (AUA) 2015 Annual Meeting.

Mirabegron, a beta-3 adrenergic agonist already approved by the US Food and Drug Administration, has a different mechanism of action than previously approved pharmacologic therapies, which "raised the obvious possibility of combination treatment," Dr Drake explained.

Many clinicians have been trying out combination therapy since the approval of mirabegron, but no safety or efficacy data are available, said Deborah Lightner, MD, from the Mayo Clinic in Rochester, Minnesota, who is on the AUA guidelines committee for overactive bladder.

"I'm really pleased they did this head-to-head study," she told Medscape Medical News. But "I'm not quite sure that the results are as impressive as they want them to be."

Patients were randomized to one of three treatments: a combination regimen consisting of solifenacin 5 mg plus mirabegron 25 mg for the 4 weeks followed by mirabegron 50 mg for 8 weeks; monotherapy with solifenacin 5 mg for 12 weeks; or monotherapy with solifenacin 10 mg for 12 weeks.

The BESIDE Study

All 2172 participants who completed the study experienced symptoms of overactive bladder for at least 3 months. After a 2-week washout period, they received a month-long course of solifenacin 5 mg daily, but still experienced at least one incontinence episode.

The decrease in mean daily incontinence episodes was significantly greater in the combination group than in the 5 mg monotherapy group (1.84 vs 1.55; P = .001), but was not significantly different in the 10 mg monotherapy group (1.67).

The decrease in the mean number of daily micturitions was also greater in the combination group than in the 5 mg monotherapy group (1.59 vs 1.14). Overall, the combination was noninferior to 10 mg monotherapy, but it was superior for daily reduction in micturitions.

The reduction in the number and frequency of leaks was significant with the combination, but "is that clinically meaningful? I'm not sure we know from the study," said Dr Lightner.

Reduction in Adverse Effects

There were fewer adverse effects with the combination, although at least one treatment-emergent adverse event was reported by 36% of the combination group, 33% of the 5 mg monotherapy group, and 39% of the 10 mg monotherapy group. The most common events were dry mouth, constipation, and peripheral edema.

"The dry mouth rate was noticeably better for the combination therapy than for solifenacin 10 mg," Dr Drake reported. The rate of constipation was similar in all groups, and there were no acute retention incidents.

"The treatments are compatible with known problems with the individual monotherapies, with no problems in vital signs," Dr Drake reported.

A reduction in adverse effects — in particular dry mouth — could be a huge benefit, said Dr Lightner.

This study shows that "you can avoid higher doses of an antimuscarinic and achieve at least the same result," she told Medscape Medical News. That could mean that patients are more likely to stay on therapy, Dr Lightner pointed out.

Having studies of the drug therapies is good, "but I don't want to lose sight of the fact that this is an industry-sponsored trial," she added.

Medications should not be considered in isolation, said Dr Lightner. "Behavioral therapy is the primary effective therapy for patients with overactive bladder."

This study was funded by Astellas Pharma. Dr Drake reports financial relationships with Allergan, Astellas, and Ferring. Dr Lightner has disclosed no relevant financial relationships.

American Urological Association (AUA) 2015 Annual Meeting: Abstract PII-LBA9. Presented May 17, 2015.


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