The Role of Bacteriuria Urinary Cytokines in the Response to Onabotulinum toxin A

Objectives: To compare proportion of patients with asymptomatic bacteriuria (ASB) and baseline differences in inflammatory cytokines and chemokines between patients who respond to Onabotulinumtoxin A (BTX-A) for refractory overactive bladder (OAB) as compared to non-responders. We hypothesize that patients with poor response to intradetrusor BTX-A will be more likely to have bacteriuria and will have higher levels of urinary proinflammatory markers as compared to those with an effective response.

Methods: This is a prospective cohort study of patients who were assigned female at birth women undergoing intradetrusor BTX-A injection for refractory idiopathic urinary urgency incontinence from 2021 to 2023. Participants completed the Urinary Distress Inventory Short Form (UDI-6) on the day of injection and again 30 days after BTX-A injection. Transurethral catheterized specimen was collected for urine culture and inflammatory cytokine analysis, and all participants had to answer “No” to the question “Do you feel like you have a UTI today?”. We defined responder status as a change of ≥11 on the UDI-6 questionnaire [minimally important clinical difference (MICD)]. Our primary outcome was the proportion of responders with and without ASB. Our secondary outcome included differences in baseline inflammatory markers at the time of BTX-A injection. We performed t-tests or Wilcoxen tests, and Chi-Square/Fisher’s Exact for continuous and categorical variables, respectively. We considered a p-value of < 0.05 to be statistically significant for demographic variables with a Dunn-Sidak correction for multiple comparisons for urinary markers.

Results: Of the 75 participants who had post-injection UDI-6 data, 45 (60%) were responders and 30 (40%) were non-responders, and 28 participants (37%) had ASB. Participants with baseline ASB were older than those without (75.5 ± 7.4 years vs 64.4 ± 13.2 years, p=0.02) but otherwise did not differ in their demographic characteristics including vaginal estrogen use and history of recurrent UTI. There was no difference in treatment response when comparing participants with and without ASB [n=17 (37.8%) responders vs n=11 (40.7%) non-responders, p=0.09). Response groups did not differ in baseline characteristics apart from age (66.0 ± 14.2 years for responders vs 74.3 ± 7.8 years for non-responders, p< 0.01). After controlling for age, no proinflammatory markers were found to be predictive of treatment response. Interestingly, when controlling for variance in cytokine expression in IL-6, age remained a significant predictor of responder status. However, this is not true of the other markers we assessed.

Conclusions: We did not find a statistically significant difference in responder status based on presence of ASB in women being treated with BTX-A. Likewise we did not find a correlation with our proinflammatory testing and treatment response. Similar comparative analyses should be performed with a larger sample size, but our results suggest that those with ASB should have similar outcomes to those without.