Second-Line Treatments for OAB
Antimuscarinics. In adults, the AUA/SUFU guideline recommends the following oral antimuscarinics (listed in alphabetical order, no hierarchy implied): darifenacin (Enablex), fesoterodine (Toviaz), oxybutynin (Ditropan, Ditropan XL), solifenacin (Vesicare), tolterodine (Detrol LA), and trospium (Sanctura). Extended-release (ER) formulations are preferred over immediate-release (IR) due to a lower rate of dry mouth. Transdermal oxybutynin may also be offered. To improve outcomes in patients with issues related to efficacy or tolerability, the dose may be modified or a different antimuscarinic prescribed.4
Antimuscarinics have comparable efficacy and safety.4,13 The choice of medication depends on the patient’s history of prior antimuscarinic use, adverse events (AEs), patient preferences, comorbidities, use of other medications, and the availability of specific medications.4 AEs, particularly dry mouth and constipation, are commonly cited as the reason for the common discontinuation of antimuscarinics, warranting precaution (Table 2).
Frailty in elderly patients may encompass mobility deficits, weight loss, weakness, and cognitive deficits.4,14 Medications in older people can have a lower therapeutic index and a higher AE profile, and the effects of polypharmacy should be considered.4 The elderly are more prone to the cognitive deficits of antimuscarinics.15 In patients with dementia, antimuscarinics are contraindicated or must be used with extreme caution.16
Beta3-agonists. Selective beta3- agonists for OAB avoid activation of the ß1– and ß2-adrenergic receptor as well as undesirable AEs such as increased heart rate and muscle tremors.4 The ß3-agonist mirabegron (Myrbetriq 25 mg and 50 mg) was approved for OAB in the United States in 2012 for once-daily use (after the initial AUA/SUFU guideline was published; included in the newly revised Guideline) (Figure 1). No dry mouth or constipation is seen, but patients should be monitored for hypertension (see Patient-Clinician Video B with Dr. Ginsberg).
Pooled analysis of phase 3 studies showed mean change from baseline in the number of incontinence episodes per 24 hours was better with mirabegron 50 mg vs. placebo (-1.48 vs. -1.09); also reduced was mean number of micturitions per 24 hours, -1.77 vs. -1.18, respectively; the number of severe urgency episodes (grade 3 or 4) per 24 hours (-1.93 vs. -1.20); and number of UUI episodes per 24 hours (-1.28 vs. -0.93; all P<0.05). Patients in all mirabegron groups combined had approximately twice the rate of hypertension as those receiving placebo.17
Third-Line Treatments for OAB
Sacral neuromodulation (InterStim®).This device stimulates the S3 nerve to “modulate” inappropriate reflexes. Following first-stage stimulation, if patients show >50% improvement, a permanent implant involving minor surgery may be considered.
Patients 5 years postimplant18,19 have shown >50% improvement in 68% of patients with UI and >50% improvement in the 56% of those with urgency-frequency.19 The success rate for refractory UUI was 87% at 1 month and 62% at 5 years, with 80% of patients still using sacral neuromodulation at 5 years.18
In a prospective, randomized, multicenter trial evaluating the 6-month success rate of sacral neuromodulation vs. standard medical therapy in 147 patients with mild-to-moderate OAB symptoms, the sacral neuromodulation group showed significant improvements in quality of life (QoL) vs. the standard medical therapy group (all P < 0.001). Also, 86% of sacral neuromodulation subjects reported improved or greatly improved urinary symptom interference score at 6 months vs. 44% for standard medical therapy subjects.20
Percutaneous Tibial Nerve Stimulation (PTNS). The only approved PTNS system (Urgent® PC) is a minimally invasive neuromodulation system that provides retrograde electrical stimulation of the sacral nerve plexus. The system targets specific neural tissue and “jams” the pathways transmitting unwanted signals. The OrBIT (Overactive Bladder Innovative Therapy) trial found both PTNS and tolterodine ER to be equally effective in 100 patients.21 PTNS responders in the OrBIT trial were treated for an additional 9 months, with improved efficacy seen at 12 months.22