The much-anticipated 39th Annual Meeting of the European Urological Association (EAU24) in 2024 has come to a successful conclusion. As the largest and most influential urology academic event in Europe, this EAU24 has undoubtedly set a new benchmark in the international urology community, and its influence is increasing day by day. In this conference, the editor has compiled 2 hot studies focusing on the treatment of bladder pain syndrome/interstitial cystitis, let's take a look.
A0237: A Prospective Study to Investigate the Efficacy and Safety of Intervesical Interferon in the Treatment of Refractory Bladder Pain Syndrome/Interstitial Cystitis
1. Background
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and distressing condition that can significantly reduce the quality of life of patients. Despite numerous studies, the exact etiology and underlying mechanisms of IC remain unclear, leading to challenges in diagnosis and treatment. The researchers proposed the role of viral infection in IC/BPS and found the presence of BK polyomavirus (BKPyV) and JCPyV in the urine of IC/BPS patients, which may be the original pathogens responsible for the development of IC/BPS. Interferon is involved in the antiviral response and can inhibit JCPyV and BKPyV infection. Therefore, interferon may be a potential treatment for IC/BPS. This study is the first to investigate the efficacy and safety of interferon intravesical infusion in patients with IC/BPS.
2. Research methods
Women with a diagnosis of IC/BPS but no urinary tract infection or neoplasm between October 2022 and March 2023, patients who meet the inclusion and exclusion criteria were included in this study after approval by the local ethics committee. Patients were treated with bladder interferon α-2b once weekly for four weeks, followed by monthly perfusions for four months for a total of eight perfusions in a course of treatment. The primary outcomes included 24-hour voiding frequency, nocturia frequency, bladder functional capacity, interstitial cystitis symptom index score (ICSI), interstitial cystitis problem index score (ICPI), and pain visual analogue scale (VAS). Adverse events were also recorded.
3 Research results
A total of 23 patients were included, and none withdrew from treatment. At the 6-month follow-up, the number of 24-hour voids was significantly reduced by 7.1 times, the number of nocturia was reduced by 1.9 times, the bladder functional capacity was increased by 47.4 ml, the ICSI was reduced by 3.9 points, the ICPI was reduced by 2.8 points, and the pain VAS was reduced by 3.2 points. No serious adverse events were reported.
4. Conclusions of the study
The rationale for exploring interferon therapy lies in the growing body of evidence that the virus is involved in the pathogenesis of IC/BPS. These results suggest that intravesical interferon may be a potentially effective and safe treatment for patients with IC/BPS.
A0245: A Phase 1/2a study preliminarily demonstrated that Brimapitide (BRM) is a potential new therapy for BPS/IC with a favorable safety profile
1. Background
BRM is a protease-resistant peptide capable of crossing cell membranes and infiltrating into cells, selectively blocking JNK MAPK cascades associated with autoimmune and inflammatory diseases. Therefore, compounds that inhibit the JNK pathway may provide considerable therapeutic value in BPS/IC. Topical administration allows active concentrations to be carried out in the area of the disease while limiting the possibility of systemic side effects.
2. Research methods
This open-label Phase 1/2a study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of BRM in subjects with BPS/IC± Hunner lesion (HL) and a numeric pain rating scale (NRS) score of 5-8, and the study has been approved by the local health authority and ethics committee. The study consisted of a 2-week screening period and a 10-week treatment period, during which Cohort 1 (C1) participants received escalating doses (5, 10, 25, 50, and 100 mg) of bladder infusion every 2 weeks. Dose escalation is determined by PK and safety. Safety and tolerability were investigated over the course of the study, and efficacy outcomes (assessment of pain, severity of HL, and patient's health status) were evaluated 1 week after the last perfusion. Cohort 2 (C2) explored the efficacy and safety outcomes of a higher dose (200mg) administered weekly.
3 Research results
A total of 13 subjects and 7 subjects were included in C1 and C2, with similar baseline characteristics. One participant in each cohort dropped out of the study due to the technical inability to obtain PK samples. In C2, 4 subjects stopped treatment early and 2 completed the study due to out-of-spec values found during stability testing (not considered a safety concern). In C1, the mean age was 59 years, the BMI was 28.6 kg/m2, and the baseline pain score was 6.6. Seventy-eight per cent of participants were women. 98% of the PK samples were < lower limit of quantification (LLOQ), and the rest were 100-fold lower than the safe level. BRM was well tolerated, with 17 treatment-emergent adverse events (TEAEs) reported in 9 participants, 76% mild, 24% moderate, and no serious adverse events (SAEs). BRM reduced participants' pain scores by 27% and resulted in a reduction in ICSI/ICPI scores (21%/15%). Sixty-seven percent of respondents reported an improvement in the Global Response Assessment Form (GRA) score. Blinded lesion grading by one examiner showed improvement during treatment in 6/10 of participants. In C2, all PK samples were <LLOQ, and 13 TEAEs were reported in 4 participants, of which 85% were mild and 15% were moderate, with no SAEs reported.
4. Conclusions of the study
BRM is generally safe and well tolerated after intravesical administration in subjects with BPS/IC. PK analysis confirmed that systemic exposure was minimal and that systemic side effects were unlikely. BRM has shown clinically relevant effects in reducing pain, and the results support further investigation as a novel treatment option for BPS/IC.
Resources:
[1] Resource Centre - EAU24 (uroweb.org)
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