Low-dose azathioprine or mercaptopurine in combination with allopurinol can bypass many adverse drug reactions in patients with inflammatory bowel disease
Low-dose azathioprine or mercaptopurine in combination with allopurinol can bypass many adverse drug reactions in patients with inflammatory bowel disease
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DOI：
10.1111/j.1365-2036.2009.04221.x
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发表时间：
2010-03-15
影响因子：
7.6
通讯作者：
Florin, T. H. J.
中科院分区：
文献类型：
--
作者：
Ansari, A.;Patel, N.;Florin, T. H. J.
背景硫嘌呤类药物硫唑嘌呤和巯基嘌呤（MP）是治疗IBD的常用药物。然而，治疗失败所造成的药物不良反应happened.AimTo研究别嘌呤醇与减少剂量的巯基嘌呤的组合，试图避免药物不良反应，在治疗IBD.MethodsPatients药物反应，以全剂量巯基嘌呤被招募在两个IBD中心的联合治疗，在这个回顾性研究。通过测量硫嘌呤甲基转移酶（英国患者）或硫鸟嘌呤核苷酸和甲基-6MP（澳大利亚患者）指导给药。反应监测临床活动indics.ResultsOf 41例患者，25例非肝和16例肝炎反应。32例患者（78%）实现了临床缓解，中位随访时间为41周（范围0.5-400）。对联合治疗无反应的患者倾向于早期失败，并出现相同的不良反应。在最高四分位数范围内，甲基-6MP发生不良反应的相对风险为2.7在下三个四分位数中，甲基-6MP的（1.3-28）倍（95%置信区间）。结论来自我们中心的联合经验是IBD中该联合治疗策略的最大报告经验，首次提供证据证明硫嘌呤和别嘌呤醇联合治疗可避免非肝炎药物不良反应。
BackgroundThe thiopurine drugs, azathioprine and mercaptopurine (MP), are established treatments for IBD. However, therapeutic failure caused by adverse drug reactions occurs frequently.AimTo study combination of allopurinol with reduced-dose thiopurine in an attempt to avoid adverse drug reactions in the treatment of IBD.MethodsPatients with drug reactions to full-dose thiopurines were recruited for combination therapy in two IBD centres in this retrospective study. Dosing was guided by measuring thiopurine methyltransferase (for UK patients) or thioguanine nucleotides and methyl-6MP (Australian patients). Response was monitored by clinical activity indices.ResultsOf 41 patients, 25 had non-hepatic and 16 had hepatitic reactions. Clinical remission was achieved in 32 patients (78%) with a median follow-up of 41 weeks (range 0.5-400). Patients who did not respond to combination therapy tended to fail early with the same adverse reaction. The relative risk of having an adverse reaction with methyl-6MP in the top interquartile range was 2.7 (1.3-28) times that with methyl-6MP in the lower three quartiles (95% confidence interval).ConclusionThe combined experience from our centres is the largest reported experience of this combination therapy strategy in IBD, and the first to provide evidence for benefit in thiopurine and allopurinol co-therapy to avoid non-hepatitic adverse drug reactions.