Interstitial cystitis/bladder pain syndrome (IC/BPS) is a rare, chronic inflammatory condition of the bladder. Recently, Hunner type IC represents a distinct disease process that requires different management strategies. In a systematic review, glycosaminoglycan (GAG) substitution instillation was found to be a valuable option with limited evidence.  Another option is endoscopic ablation of the Hunner lesion directly. After ablation of the Hunner lesion, pain-related symptoms improved significantly, but the efficacy was not long-lasting due to the 2-year recurrence rate was as high as 75%. We hypothesized that intravesical instillation of hyaluronic acid and chondroitin sulfate (HACS), a GAG substitute, following transurethral ablation of Hunner lesions may reduce recurrence and prolong recurrence-free time compared to transurethral ablation alone.

This was a single-center, prospective, single-arm study in which the treatment group was compared to a historical control group. The eligible participants were patients aged > 20 years with IC/BPS who had bladder pain with a pain visual analogue scale (VAS) of 4 or higher lasting for more than 6 months and Hunner lesions confirmed through cystoscopy, who were scheduled to undergo transurethral ablation. One month after surgery, patients underwent intravesical HACS instillation and were followed-up for 2 years (HACS group). Patients in the HACS group received a sterile solution containing 800 mg/50 mL sodium hyaluronic acid (HA) (1.6%) and 1g/50mL sodium chondroitin sulfate (CS) (2%) (HACS; iAluiRil® Prefill; IBSA, Lodi, Italy) via weekly intravesical instillation for 4 weeks, once every 2 weeks for 8 weeks, and then monthly for 2 months (a total of 10 times). The historical control group consisted of patients who were registered in our institute’s IC/BPS registry and were followed up for a total of 2 years after receiving transurethral ablation of the Hunner lesions. The primary outcome was whether the recurrence rate decreased to ≤ 60% in the HACS group. Recurrence was defined as a case in which pain returned to the baseline level and identification of Hunner lesion on cystoscopy. The secondary outcomes included recurrence rate and recurrence-free time between the groups, changes in voiding symptoms from baseline using the 3-day voiding diary parameters, and changes in the quality of life and symptom severity from baseline assessed using the O’Leary-Sant IC symptom index (ICSI) and problem index (ICPI), pelvic pain and urgency/frequency (PUF) symptom scale, and visual analogue scale for pain.

Patients were enrolled from September 2017 to October 2019, and the 2-year follow-up was concluded in November 2021. A total of 78 patients were enrolled, and 51 were included in the per-protocol analysis set. The 2- year recurrence rate was 47.1% (95% CI, 32.9 to 61.5) in the HACS group and 86.2% (95% CI, 74.6 to 93.9) in the control group (P<0.001). In the multivariable logistic regression model, which included four confounders: age, gender, number of Hunner lesions and PUF symptom scale, only HACS instillation (odds ratio, 0.13; 95% CI, 0.05 to 0.35, P<0.001) was associated with a lower proportion of recurrence. The median follow-up time for the HACS group was 23.3 months (95% CI, 23.1 to 23.7) and for control group was 27.6 months (95% CI, 23.7 to 31.0). The HACS group had increased recurrence-free survival with the median interval not reached. In contrast, the control group had a median survival of 11.4 months (95% CI, 8.8 to 13.8, P<0.001) (Fig. 1). After adjusting the effect of confounders, the risk of recurrence was 61.7% lower in the HACS group than in control group (hazard ratio, 0.38; 95% CI, 0.23 to 0.65; P<0.001).  Regardless of the instillation treatment, there were significant improvements in all symptom questionnaire scores and pain compared to the baseline. However, in the HACS group, improvement was stable even after 12 months. Both the groups showed the lowest levels of daytime frequency, nocturia and urgency episodes 1 month after surgery. The differences in the voiding diary parameters between the control and HACS groups were not significant at any time. However, from 12 to 24 months, the degree of improvement in the daytime frequency, number of nocturia, and urgency episodes in the HACS group were greater than those in the control group, and more patients showed a tendency to maintain well.

In this prospective study involving patients with Hunner type IC, the recurrence rate was significantly lower among patients who received intravesical HACS instillation treatment after transurethral ablation of the Hunner lesion than among those who underwent ablation only. The patients' subjective symptoms showed significant improvement only with surgical treatment, but the maintenance period of the improved condition tended to increase in the HACS group. Among the treatment methods known to date, intravesical HACS instillation after transurethral ablation of the Hunner lesions is the most effective treatment for Hunner type IC through structural and functional regeneration of the bladder as well as improvement of subjective symptoms.

In patients with Hunner type IC, intravesical instillation of HACS after transurethral ablation significantly reduced the recurrence rate and maintained symptom improvement for more than 1 year.

Continence 7S1 (2023) 100819
DOI: 10.1016/j.cont.2023.100819