Optimising outcome on thiopurines in inflammatory bowel disease by co-prescription of allopurinol
Optimising outcome on thiopurines in inflammatory bowel disease by co-prescription of allopurinol
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DOI：
10.1016/j.crohns.2012.02.007
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发表时间：
2012-10-01
影响因子：
8
通讯作者：
Sanderson, Jeremy D.
中科院分区：
文献类型：
--
作者：
Smith, Melissa A.;Blaker, Paul;Sanderson, Jeremy D.
背景和目的：硫唑嘌呤和巯嘌呤仍然是炎症性肠病的一线免疫调节治疗方法。毒性和无反应是重要问题。别嘌呤醇与减少剂量（25-33%）硫唑嘌呤或巯嘌呤的联合处方可以克服这些问题。我们在一个大型单中心队列中展示了联合处方的结果。方法：确定了接受硫嘌呤/别嘌呤醇联合处方的患者。确定了联合治疗的适应症和结果。比较单药治疗和联合治疗的血液参数和代谢结果。寻找与联合治疗相关的毒性。结果：确定了 110 名接受联合治疗的患者。在可以单独研究硫嘌呤效果的患者中，60/79 (76%) 的患者获得了临床缓解。 20/25 的肝毒性患者耐受联合治疗并使肝功能测试正常化。 24/28 的非典型副作用患者可以耐受联合治疗。 13/20 的无反应者对联合治疗有反应。在开始接受联合治疗作为一线治疗的患者中，15/23 实现了临床缓解。联合治疗时硫鸟嘌呤核苷酸显着升高，甲基化代谢物显着降低。联合治疗的平均细胞体积较高，总白细胞和中性粒细胞计数较低。发生了 13 例不良事件，其中 6 例是联合治疗特有的（3 例皮疹、2 例肝功能检查异常、1 例剂量错误）。所有症状都很轻微且具有自限性。结论：这是使用别嘌呤醇优化硫嘌呤治疗结果的最大的已发表经验。联合治疗使大量患者获得成功治疗，否则这些患者将被标记为硫嘌呤治疗失败。遇到了一些自限性副作用。 (C) 2012 年欧洲克罗恩病和结肠炎组织。由 Elsevier B.V. 出版。保留所有权利。
Background and aims: Azathioprine and mercaptopurine remain first line immunomodulatory treatments for inflammatory bowel disease. Toxicity and non-response are significant issues. Co-prescription of allopurinol with reduced-dose (25-33%) azathioprine or mercaptopurine may overcome these problems. We present the outcome of co-prescription in a large single-centre cohort.Method: Patients on thiopurine/allopurinol co-prescription were identified. Indication for and outcome on combination treatment were established. Blood parameters and metabolite results were compared on single agent and combination treatment. Toxicity associated with combination treatment was sought.Results: 110 patients on combination treatment were identified. Clinical remission was achieved in 60/79 (76%) of patients in whom the effect of thiopurine could be studied in isolation. 20/25 patients with hepatotoxicity tolerated combination treatment and normalised their liver function tests. 24/28 patients with atypical side effects tolerated co-therapy. 13/20 non-responders responded to combination treatment. In patients started on combination treatment as first line therapy, 15/23 achieved clinical remission. Thioguanine nucleotides were significantly higher and methylated metabolites significantly lower on combination therapy. Mean cell volume was higher and total white cell and neutrophil counts lower on combination treatment. 13 adverse events occurred, including 6 specific to co-therapy (3 rash, 2 abnormal liver function tests, 1 dosing error). All were minor and self-limiting.Conclusion: This is the largest published experience of the use of allopurinol to optimise outcomes on thiopurine treatment. Combination therapy permitted successful treatment of a significant number of patients who would otherwise have been labelled as thiopurine failures. A few self-limiting side effects were encountered. (C) 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.