Cassinotti Andrea, Actis Giovanni C, Duca Piergiorgio, Massari Alessandro, Colombo Elisabetta, Gai Elisa, Annese Vito, D'Albasio Giuseppe, Manes Gianpiero, Travis Simon, Porro Gabriele Bianchi, Ardizzone Sandro
Department of Clinical Sciences, Gastroenterology Unit, Luigi Sacco University Hospital, Milano, Italy.
Am J Gastroenterol. 2009 Nov;104(11):2760-7. doi: 10.1038/ajg.2009.410. Epub 2009 Jul 21.
Whether the duration of maintenance treatment with azathioprine (AZA) affects the outcome of ulcerative colitis (UC) is unclear. We investigated clinical outcomes and any predictive factors after withdrawal of AZA in UC.
In this multicenter observational retrospective study, 127 Italian UC patients, who were in steroid-free remission at the time of withdrawal of AZA, were followed-up for a median of 55 months or until relapse. The frequency of clinical relapse or colectomy after AZA withdrawal was analyzed according to demographic, clinical, and endoscopic variables.
After drug withdrawal, a third of the patients relapsed within 12 months, half within 2 years and two-thirds within 5 years. After multivariable analysis, predictors of relapse after drug withdrawal were lack of sustained remission during AZA maintenance (hazard ratio, HR 2.350, confidence interval, CI 95% 1.434-3.852; P=0.001), extensive colitis (HR 1.793, CI 95% 1.064-3.023, P=0.028 vs. left-sided colitis; HR 2.024, CI 95% 1.103-3.717, P=0.023 vs. distal colitis), and treatment duration, with short treatments (3-6 months) more disadvantaged than >48-month treatments (HR 2.783, CI 95% 1.267-6.114, P=0.008). Concomitant aminosalicylates were the only predictors of sustained remission during AZA therapy (P=0.009). The overall colectomy rate was 10%. Predictors of colectomy were drug-related toxicity as the cause of AZA withdrawal (P=0.041), no post-AZA drug therapy (P=0.031), and treatment duration (P<0.0005).
Discontinuation of AZA while UC is in remission is associated with a high relapse rate. Disease extent, lack of sustained remission during AZA, and discontinuation due to toxicity could stratify relapse risk. Concomitant aminosalicylates were advantageous. Prospective randomized controlled trials are needed to confirm whether treatment duration is inversely associated with outcome.
硫唑嘌呤（AZA）维持治疗的时长是否会影响溃疡性结肠炎（UC）的结局尚不清楚。我们调查了UC患者停用AZA后的临床结局及任何预测因素。
在这项多中心观察性回顾性研究中，127例意大利UC患者在停用AZA时处于无类固醇缓解状态，随访时间中位数为55个月或直至复发。根据人口统计学、临床和内镜变量分析停用AZA后临床复发或结肠切除术的频率。
停药后，三分之一的患者在12个月内复发，一半在2年内复发，三分之二在5年内复发。多变量分析后，停药后复发的预测因素包括AZA维持治疗期间未实现持续缓解（风险比，HR 2.350，95%置信区间，CI 1.434 - 3.852；P = 0.001）、广泛性结肠炎（HR 1.793，95% CI 1.064 - 3.023，与左侧结肠炎相比P = 0.028；HR 2.024，95% CI 1.103 - 3.717，与远端结肠炎相比P = 0.023）以及治疗时长，短期治疗（3 - 6个月）比治疗时长>48个月的患者更易复发（HR 2.783，95% CI 1.267 - 6.114，P = 0.008）。同时使用氨基水杨酸类药物是AZA治疗期间持续缓解的唯一预测因素（P = 0.009）。总体结肠切除术率为10%。结肠切除术的预测因素包括因药物相关毒性而停用AZA（P = 0.041）、停用AZA后未进行药物治疗（P = 0.031）以及治疗时长（P < 0.0005）。
UC缓解期停用AZA与高复发率相关。疾病范围、AZA治疗期间缺乏持续缓解以及因毒性而停药可对复发风险进行分层。同时使用氨基水杨酸类药物具有优势。需要进行前瞻性随机对照试验来证实治疗时长是否与结局呈负相关。
