Crescenze Iryna M, Tucky Barbara, Li Jianbo, Moore Courtenay, Shoskes Daniel A
Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH.
Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH.
Urology. 2017 Sep;107:49-54. doi: 10.1016/j.urology.2017.05.016. Epub 2017 May 18.
To evaluate the efficacy of oral cyclosporine A (CyA) in the treatment of refractory interstitial cystitis-bladder pain syndrome (IC-BPS) and to assess safety using drug level and renal function monitoring.
Patients with IC-BPS who failed at least 2 prior treatments were enrolled in an open-label study of oral CyA. Medication was started at 3 mg/kg divided twice daily for 3 months. Dose was adjusted based on side effects and the drug level was measured 2 hours after the morning dose (C2). The primary end point was moderate or marked improvement of global response assessment or >50% improvement on the Interstitial Cystitis Symptom Index (ICSI) or Interstitial Cystitis Problem Index at 3 months.
Twenty-two of 26 patients completed the 3-month follow-up; 18 completed the poststudy evaluation. The median symptom duration was 66 months (12-336). At 3 months, 31% (8/26) improved by global response assessment, 15% (4/26) had >50% improvement in the ICSI score, and 19% (5/26) had an improvement in the Interstitial Cystitis Problem Index score. Hunner lesions (HLs) predicted an improvement in the ICSI score (odds ratio = 15.4, 95% confidence interval: 1.7-224.6, P = .01), with 75% (3/4) of the responders having HL. Two patients withdrew because of hypertension or elevated serum glucose. The mean nuclear glomerular filtration rate declined at 3 months (98.9 ± 31.6 vs 84.2 ± 25.5 mL/min/1.73 m, P = .01) and reversed to baseline after discontinuation of treatment. C2 levels did not correlate with symptoms but allowed dose reduction in 11 patients.
Per American Urological Association guidelines, CyA can be effective in a proportion of patients with refractory IC-BPS. Patients with HL are more likely to benefit. Monitoring of C2 rather than trough levels can lead to dose reduction, thereby minimizing toxicity.
评估口服环孢素A（CyA）治疗难治性间质性膀胱炎-膀胱疼痛综合征（IC-BPS）的疗效，并通过药物水平和肾功能监测评估其安全性。
将至少经过2次先前治疗失败的IC-BPS患者纳入口服CyA的开放标签研究。药物开始剂量为3mg/kg，分两次服用，共3个月。根据副作用调整剂量，并在晨服后2小时测量药物水平（C2）。主要终点是3个月时总体反应评估为中度或显著改善，或间质性膀胱炎症状指数（ICSI）或间质性膀胱炎问题指数改善>50%。
26例患者中有22例完成了3个月的随访；18例完成了研究后评估。症状持续时间的中位数为66个月（12-336个月）。3个月时，根据总体反应评估，31%（8/26）的患者有所改善，15%（4/26）的患者ICSI评分改善>50%，19%（5/26）的患者间质性膀胱炎问题指数评分有所改善。Hunner溃疡（HLs）预示ICSI评分会改善（优势比=15.4，95%置信区间：1.7-224.6，P=0.01），75%（3/4）的有反应者有HL。2例患者因高血压或血糖升高而退出。3个月时平均肾小球滤过率下降（98.9±31.6 vs 84.2±25.5 mL/min/1.73 m²，P=0.01），停药后恢复至基线水平。C2水平与症状无关，但可使11例患者减少剂量。
根据美国泌尿外科学会指南，CyA对一部分难治性IC-BPS患者可能有效。有HL的患者更可能获益。监测C2而非谷值水平可导致剂量减少，从而将毒性降至最低。
