Secondary Analysis of Interstitial Cystitis/Bladder Pain Syndrome Patients Enrolled in a Recurrent Urinary Tract Infection Prevention Study Provides a Novel Paradigm for Etio-Pathogenesis and Practical Management of This Infection Phenotype

Introduction: A subset of interstitial cystitis/bladder pain syndrome (IC/BPS) patients experience recurrent urinary tract infection (rUTI) associated with symptom flares. Recurrent UTI subjects with associated IC/BPS were enrolled in the first North American early clinical experience trial evaluating a new sublingual UTI preventative vaccine, MV140. It has been shown that women with rUTI develop an imbalance in the T helper 1 and 2 (Th2 over-expression) in the bladder mucosa. Our hypothesis-generating secondary analysis will suggest that this infection subcategory of IC/BPS patients develop a similar imbalance of Th1-Th2 response type to bacteria present in their urinary microbiome, leading to a bladder hypersensitivity that responds to mucosal immune modulation. Methods: Female participants with >= 3 documented UTI/year underwent a 3-month vaccination treatment period with a 9-month efficacy period after completion of vaccine treatment (total 12 months). There were no exclusion criteria for subjects in relation to baseline urinary symptoms and/or discomfort/pain. Primary outcome was no UTI following vaccination. Secondary outcomes included change in UTI incidence, overall patient-reported subjective global assessment (SGA responder defined as moderately or markedly improved on 7-point scale), and safety. Results: Sixteen subjects with IC/BPS-related symptoms and rUTI (mean age 47; range 23-74 years; mean number of UTI episodes in previous year 6.1 +/- 4.2) were eligible to be included in the Health Canada-approved MV140 vaccine study for prevention of rUTI. All subjects completed the 3-month vaccination period. One subject was lost to follow-up after their 6-month visit. Six subjects were UTI-free, while all 16 subjects had a reduction in UTI episodes compared to the year pre-vaccination. The total post-vaccination reduction in UTI episodes compared to pre-vaccination was 80% (0.1 UTI/subject/month from 0.5 UTI/subject/month, respectively). At 12 months, 13 subjects (81%) were SGA responders (moderately or markedly improved), and the responders reported a reduction in IC/BPS symptoms, with 8 subjects reporting significant or almost complete resolution of their specific long-term bladder discomfort/pain and bothersome urinary frequency or urgency. Four subjects reported mild and self-limited adverse events during vaccination period, but none were related to MV140 vaccine. Conclusion: Sublingual MV140 vaccine in IC/BPS patients with rUTI not only achieved UTI-free or reduced UTI incidence status but also, after approximately 9 months post vaccination, resolution of patients' long-term treatment-refractory IC/BPS symptoms. This suggests some cases of IC/BPS may be etiologically based on Th2-driven hypersensitivity to bacteria within or entering the urinary microbiome that responds to a vaccine whose mechanism of action is to normalize or balance the bladder Th1/Th2 mucosal immune system.