Treatment of overactive bladder follows an algorithmic pathway, starting with conservative measures and medications and culminating in third-line therapies, such as posterior tibial nerve stimulation, sacral neuromodulation and intradetrusor onabotulinumtoxinA injections (BTX-A). Although these have high success rates, the literature is sparse on how to manage third line therapy failures. We examined practice patterns regarding patients who failed BTX-A performed in a tertiary care center.

All patients undergoing intradetrusor BTX-A injection for neurogenic and non-neurogenic overactive bladder at a tertiary care center from 2016-2018 were retrospectively reviewed. Patient demographics and clinical information including age, gender, race, body mass index, procedural indication, BTX-A dose, subjective improvement, interval between injections, adverse events, follow up, and subsequent therapies were recorded. Failure of initial BTX-A injection was defined as an unsatisfactory subjective response after a maximum of two injections. Lost to follow up was defined as no patient contact for at least 6 months after initial BTX-A injection. Adverse events included 30 day readmission, urinary tract infection and urinary retention requiring catheterization. Appropriate statistical tests were performed.

A total of 282 patients underwent 516 intradetrusor BTX-A injections. Patients were predominantly female (82.3%), with an average age of 64.2±14.5 years and body mass index of 30.8±8.3 kg/m2. 33.6% (n=95) of the population had a diagnosis of a neurogenic bladder. Among non-neurogenic patients, 88% reported overactive bladder wet symptoms. The average number of BTX-A injections per patient was 2.1 over the study period, with a failure rate of 33% and overall adverse event rate of 11.7%. No demographic differences were noticed between patients who failed and those who had successful injections. The adverse event rate for failures (16%) was not significantly higher than the successes (9.5%, p=0.12). There was also no statistically significant difference between successes and failures amongst those who had a diagnosis of a neurogenic bladder (34.9% vs 31.2%, p=0.59). Among failures, time to follow up (62.2±95.6 vs. 123±113.0 days, p<0.01) was shorter and these patients were more likely to undergo repeat injection at a higher dose (p<0.01). Of the 93 failures, 38.7% were lost to follow up. In order of decreasing frequency, the remaining patients underwent medical pharmacotherapy (including anticholinergics and beta-3 agonists), repeat intradetrusor BTX-A injections (either at the same dose or a higher dose), sacral neuromodulation, or other surgical therapy, such as an artificial urinary sphincter, bulking agent, mid urethral sling, urinary diversion, or suprapubic catheter (Table 1). No patients went on to percutaneous tibial nerve stimulation.

About one third of patients who failed BTX-A injections in this tertiary care practice were lost to follow up. Additionally, almost one quarter of the failures were re-prescribed either an anticholinergic or beta-3 agonist. Only 9 patients (9.7%) were offered sacral neuromodulation and no patients underwent percutaneous tibial nerve stimulation. When analyzing the demographics of the cohort, there was also no difference in the rate of failures amongst neurogenics or non-neurogenics. In this population, more patients were offered a second line therapy after failing a third line therapy rather than offering an alternative third line therapy, such as percutaneous tibial nerve stimulation or sacral neuromodulation.

Patients who are offered BTX-A injections have commonly already failed first and second line therapies. However, pharmacotherapy, which is a second line treatment option, was the most common next step in patients who subjectively failed BTX-A injections for neurogenic and non-neurogenic overactive bladder. Less frequently, other third line therapies were offered, such as repeat BTX-A injections, either at the same dose or a higher dose, or sacral neuromodulation. Very few patients were offered a surgical option, such as a urinary diversion. Overall, failures did not have a higher adverse rate, but were more likely to be lost to follow up.