Phenotype-oriented Multimodal Therapy for Refractory Interstitial Cystitis / Bladder Pain Syndrome in Women: a Prospective Comparative Study

Abstract

The objective: to evaluate the efficacy of phenotype-oriented multimodal pharmacotherapy for interstitial cystitis / bladder pain syndrome (IC/BPS) in women: 1) to compare triple therapy (botulinum toxin type A (BoNT/A) + gabapentin + hydroxychloroquine (HCQ)) with BoNT/A monotherapy in refractory IC/BPS; 2) to determine the efficacy of the oral combination of gabapentin + HCQ in primary IC/BPS; 3) to establish the prognostic significance of the cystoscopic phenotype for therapeutic response. Materials and methods. A prospective single-center open-label non-randomized comparative study (n = 107 women, aged 18–65 years, Interstitial Cystitis Symptom Index (ICSI) ≥ 12 points). Group 1 (G1, n = 33): primary IC/BPS – gabapentin 900 mg/day + HCQ 400 mg/day, 6 months. Group 2 (G2, n = 37): refractory IC/BPS – monotherapy with BoNT/A 200 U. Group 3 (G3, n = 37): refractory IC/BPS – BoNT/A 200 U + gabapentin + HCQ, 6 months. Cystoscopic phenotyping (Hunner/non-Hunner, European Society for the Study of Interstitial Cystitis 3C/2C) was performed prior to treatment. Primary endpoints: ICSI, Interstitial Cystitis Problem Index, visual analogue scale (VAS), functional bladder capacity (FBC). Follow-up: 12 months. Results. G2 and G3 were not significantly different (p > 0.05). After 6 months: overall efficacy 81.1% (G3) vs 54.1% (G2; p < 0.05); reduction in VAS 66.7% vs 46.8%; increase in FBC 117.0% vs 81.7%. After 12 months, the advantages of G3 persisted: VAS 3.7 ± 0.4 vs 6.3 ± 0.6 points (p < 0.05). Hunner lesion recurrence: 23.8% (G3) vs 70.0% (G2; p < 0.001). G1: efficacy 81.8%, reduction in VAS 58.6%. A non-Hunner phenotype is an independent predictor of a favorable outcome (odds ratio (OR) = 2.84; 95% confidence interval [1.38–5.86]; p = 0.004). No serious complications were reported. Conclusions. Triple therapy (BoNT/A + gabapentin + HCQ) is significantly more effective than BoNT/A monotherapy for recurrent IC/BPS over a 12-month period. The oral combination of gabapentin + HCQ shows promise as a first-line therapy for primary IC/BPS. The cystoscopic phenotype is an independent predictor of response (OR = 2.84; p = 0.004) and should be included in the standard workup for IC/BPS.