Hypothesis / aims of study
Onabotulinum toxin-A intradetrusor injection (BTX-A) has been proven to be an effective and safe therapy for treating overactive bladder (OAB) refractory to anticholinergics. Given that poor response to BTX-A therapy is uncommon but still exist, we aimed to identify whether primary non-responders could be predicted based on baseline clinical, demographic or urodynamic parameters.
Study design, materials and methods
This is a retrospective review of patients with refractory idiopathic Overactive Bladder (I-OAB) who underwent intradetrusor injection of Onabotulinum toxin-A 100 units (Botox®) at our tertiary center in Canada from January 2005 to December 2015. Response to treatment was evaluated by clinical assessment, urodynamics, and validated questionnaires (OABSS, ICIQ-SF, IIQ-7). Findings before and at 12 weeks after the first Botox injection were compared. Subjects were determined to be responders or non-responders, as defined by an increase in maximum cystometric bladder capacity (MCBC) of more than 30%. Non-responder status was confirmed by a second intradetrusor injection with neither clinical nor urodynamic improvement.
A total of 13 men and 52 women with a mean age of 70 years (range 21 to 94) were included based on availability of data to define responders. Overall, after 12 weeks, 63% (41/65) of the patients showed significant treatment response pertaining to subjective symptoms, and urodynamic variables (P<0.005). 24 patients (36%) qualified as non-responders. When comparing the two groups, analysis of pre-treatment demographic and UDS parameters revealed significant higher baseline first desire to void volume (FDV), and postvoid residual (PVR) in the non-responders (P<0.05). There were no significant differences between responders and non-responders in regard to age, gender, body mass index, OAB type (wet or dry) nor other of the measured UDS variables (Table 1). There was a trend for higher baseline bladder compliance (BC) in non-responders (18.8 ± 15.08 versus 13.3 ± 9.38 cm H2O, P = 0.0887). In a multivariate logistic regression model, no significant predictors for response could be recognized.
Interpretation of results
The results of this study demonstrate that poor responders to BTX-A had a higher FDV and PVR pre-treatment value. In these patients, 100 U BTX-A, could not achieve satisfactory clinical or urodynamic response sufficient to relieve OAB symptoms and improve health related quality of life. Their FDV values at 12 weeks did not change from baseline (141.2 ml at baseline to 132.8 ml at 12 weeks; p=0.6826). Similarly, PVR was unchanged at 12 weeks posttreatment (50.1ml at baseline to 72.3 ml at 12 weeks; p=0.1220). In responders, the baseline values for FDV and PVR were significantly less, with improvements in MCBC, MVP, MDP and BC, at 12 weeks.
The literature data further showed that intradetrusor injections of BTX-A not only increases the bladder capacity but also decreases the bladder sensation. This phenomenon may result from inhibition of sensory input and lead to a reduction in detrusor contractility. This indicates the substantial effects of BTX-A on afferent sensory fibers contributing to the clinical effectiveness of botulinum A toxin. The increased baseline PVR volume and decreased sensation of bladder filling in non-responders suggests an impairment of these nociceptive sensory fibers, which might have resulted in poor response to this therapy.