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硫鸟嘌呤用于对硫唑嘌呤/巯嘌呤不耐受或耐药的克罗恩病患者。

Tioguanine in patients with Crohn's disease intolerant or resistant to azathioprine/mercaptopurine.

作者信息

Bonaz B, Boitard J, Marteau P, Lémann M, Coffin B, Flourié B, Belaiche J, Cadiot G, Metman E-H, Cortot A, Colombel J-F

机构信息

Département d'Hépato-Gastroentérologie, CHU de Grenoble, France.

出版信息

Aliment Pharmacol Ther. 2003 Aug 15;18(4):401-8. doi: 10.1046/j.1365-2036.2003.01683.x.

Abstract

BACKGROUND

Tioguanine (TG) is an antimetabolite which may be regarded as an alternative to azathioprine (AZA)/mercaptopurine (MP) in patients with inflammatory bowel diseases.

AIMS

: To evaluate the tolerance and efficacy of TG in patients with Crohn's disease, intolerant or resistant to AZA/MP.

METHODS

An open prospective study was made on Crohn's disease patients treated with TG. Intolerance to AZA/MP was defined as a reaction occurring within 1 month after introduction of AZA/MP, including pancreatitis, abdominal pain, fever, arthralgia, myalgia, cutaneous rash, fatigue, alopecia, hepatitis and digestive intolerance. Resistance to AZA/MP was defined as the persistence of activity after at least 3 months of AZA/MP therapy.

RESULTS

Forty-nine Crohn's disease patients (36 women, 13 men; intolerance: n = 39; resistance: n= 10) were treated with TG (20 mg/day). Clinical pancreatitis did not recur under TG. Five patients (10%) had to stop TG due to intolerant reactions observed 13-21 days after TG was started. No haematological side-effects were observed under TG. The probability of clinical remission without corticosteroids or infliximab at 6 and 12 months was 46% and 79%, respectively, in the 40 patients with active disease at baseline. The probability of clinical relapse during maintenance TG therapy at 6 and 12 months was 29% and 53%, respectively, in the 28 patients in remission at baseline or who had achieved remission on TG.

CONCLUSIONS

TG is a possible alternative treatment in Crohn's disease patients, intolerant (especially for pancreatitis) or resistant to AZA/MP.

摘要

背景

硫鸟嘌呤(TG)是一种抗代谢药物,在炎症性肠病患者中可被视为硫唑嘌呤(AZA)/巯嘌呤(MP)的替代药物。

目的

评估TG对不耐受或抵抗AZA/MP的克罗恩病患者的耐受性和疗效。

方法

对接受TG治疗的克罗恩病患者进行了一项开放性前瞻性研究。对AZA/MP不耐受定义为在引入AZA/MP后1个月内出现的反应,包括胰腺炎、腹痛、发热、关节痛、肌痛、皮疹、疲劳、脱发、肝炎和消化不耐受。对AZA/MP抵抗定义为在接受AZA/MP治疗至少3个月后疾病仍持续活动。

结果

49例克罗恩病患者(36例女性,13例男性;不耐受:n = 39;抵抗:n = 10)接受了TG(20mg/天)治疗。在TG治疗期间临床胰腺炎未复发。5例患者(10%)在开始TG治疗后13 - 21天因出现不耐受反应而不得不停止治疗。在TG治疗期间未观察到血液学副作用。在基线时有活动性疾病的40例患者中,6个月和12个月时不使用皮质类固醇或英夫利昔单抗而实现临床缓解的概率分别为46%和79%。在基线时处于缓解期或在TG治疗后实现缓解的28例患者中,TG维持治疗6个月和12个月时临床复发的概率分别为29%和53%。

结论

对于不耐受(尤其是胰腺炎)或抵抗AZA/MP的克罗恩病患者,TG是一种可能的替代治疗方法。

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