Irritable bowel syndrome subtype predicts treatment response and defines distinct mechanistic phenotypes in OAB-IBS...

To investigate the heterogeneity of treatment response in patients with concomitant Overactive Bladder (OAB) syndrome and Irritable Bowel Syndrome (IBS), including diarrhea-predominant (IBS-D), constipation-predominant (IBS-C), and mixed-type (IBS-M), by stratifying outcomes by both treatment strategy and IBS subtype. We hypothesized that IBS subtype would predict therapeutic response and define distinct mechanistic phenotypes.

In this prospective, observational cohort study (N = 144, screened from 259), patients were allocated to one of four non-randomized cohorts: OAB-Targeted Monotherapy (OAB-TM, n = 45), OAB-Targeted Dual Therapy (OAB-TD, n = 29), IBS-Targeted Monotherapy (IBS-TM, n = 47), or IBS-Targeted Dual Therapy (IBS-TD, n = 23). Outcomes included changes in OABSS, IBS-SSS, PHQ-9, GAD-7, and QOL scores over 8 weeks. Efficacy was compared using ANCOVA, adjusted for baseline scores. Objective data from uroflowmetry parameters and baseline predictors of response were analyzed.

Dual therapy demonstrated superior improvement over monotherapy across all symptom, mood, and QOL domains. However, stratified analysis revealed significant heterogeneity. In the IBS-targeted cohort, the superiority of dual therapy for OAB improvement was highly significant in the IBS-D subtype but not in IBS-M or IBS-C subtypes. This corresponded to distinct baseline uroflowmetry parameters: IBS-D patients typically showed high-peak tower-shaped curves, while IBS-C patients showed staccato patterns. Furthermore, baseline anxiety (GAD-7) and depression (PHQ-9) scores significantly predicted OAB cross-organ improvement in the IBS-TM cohort.

OAB-IBS comorbidity is not a monolithic entity but comprises distinct clinical phenotypes (pelvic floor-driven, central sensitization-driven, bladder-primary). These findings suggest that a uniform treatment protocol may be suboptimal, supporting a precision-medicine framework where management is tailored based on the patient's specific IBS subtype.