Hindorf U, Johansson M, Eriksson A, Kvifors E, Almer S H C
Department of Gastroenterology and Nutrition, University Hospital, Lund, Sweden.
Aliment Pharmacol Ther. 2009 Mar 15;29(6):654-61. doi: 10.1111/j.1365-2036.2008.03925.x. Epub 2008 Dec 22.
Adverse drug reactions are a significant reason for therapeutic failure during thiopurine treatment of inflammatory bowel disease. Some smaller series in this patient population have shown that a switch to mercaptopurine may be successful in many cases of azathioprine intolerance.
To assess the long-term outcome of mercaptopurine treatment in a large patient population with azathioprine intolerance.
We identified 135 patients (74 women; median age 40 years) with Crohn's disease (n = 88) or ulcerative colitis (n = 47) and reviewed their medical records.
A total of 70 patients (52%) tolerated mercaptopurine and were followed up for 736 (362-1080) days; 65 patients discontinued mercaptopurine due to adverse events after 25 (8-92) days. Mercaptopurine was tolerated in 71% (12/17) with hepatotoxicity and in 68% (13/19) with arthralgia/myalgia during azathioprine treatment. Previous abdominal surgery was more common in mercaptopurine intolerant patients [39/65 (60%) vs. 27/70 (39%); P = 0.02] and thiopurine methyltransferase activity was higher in mercaptopurine tolerant patients than in mercaptopurine intolerant patients [13.2 (11.4-15.3) vs. 11.8 (9.6-14.2) U/mL red blood cells; P = 0.04; n = 81].
A trial of mercaptopurine should be considered in azathioprine intolerance, as half of the patients tolerate a switch to mercaptopurine. Patients with hepatotoxicity or arthralgia/myalgia during azathioprine treatment might benefit more often than those with other types of adverse events.
药物不良反应是硫唑嘌呤治疗炎症性肠病期间治疗失败的重要原因。该患者群体中的一些较小规模研究系列表明,在许多硫唑嘌呤不耐受的病例中,换用巯嘌呤可能会成功。
评估在大量硫唑嘌呤不耐受患者中使用巯嘌呤治疗的长期疗效。
我们确定了135例患有克罗恩病(n = 88)或溃疡性结肠炎(n = 47)的患者(74名女性;中位年龄40岁),并查阅了他们的病历。
共有70例患者(52%)耐受巯嘌呤,并接受了736(362 - 1080)天的随访;65例患者在25(8 - 92)天后因不良事件停用巯嘌呤。在硫唑嘌呤治疗期间出现肝毒性的患者中,71%(12/17)耐受巯嘌呤,出现关节痛/肌痛的患者中,68%(13/19)耐受巯嘌呤。既往腹部手术在巯嘌呤不耐受患者中更为常见[39/65(60%)对27/70(39%);P = 0.02],巯嘌呤耐受患者的硫嘌呤甲基转移酶活性高于巯嘌呤不耐受患者[13.2(11.4 - 15.3)对11.8(9.6 - 14.2)U/mL红细胞;P = 0.04;n = 81]。
对于硫唑嘌呤不耐受患者,应考虑试用巯嘌呤,因为有一半的患者耐受换用巯嘌呤。在硫唑嘌呤治疗期间出现肝毒性或关节痛/肌痛的患者可能比出现其他类型不良事件的患者更常从中获益。