Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia; Department of Gastroenterology, National University Hospital, Singapore.
J Gastroenterol Hepatol. 2013 Oct;28(10):1595-9. doi: 10.1111/jgh.12263.
Anti-tumor necrosis factor (TNF) antibodies are effective in maintaining remission in Crohn's disease. However, a significant proportion of patients lose response to these agents with time. This study aimed to determine whether the introduction of a thiopurine in patients who have lost response to anti-TNF monotherapy results in regained response.
Five patients (four males; aged 22-38 years) with active Crohn's disease, who had an initial response to anti-TNF therapy but had lost response, were commenced on azathioprine or mercaptopurine at standard doses while continuing anti-TNF therapy. All had previously failed thiopurine therapy prior to starting anti-TNF treatment.
All patients experienced improved clinical symptoms within 2-6 months, with benefit sustained over a mean follow-up of 19 months. Two patients with an elevated C-reactive protein at the time of thiopurine addition demonstrated a fall in C-reactive protein. Colonoscopy before and after thiopurine addition in four patients showed improvement in all, with mucosal healing achieved in two. No adverse effects of treatment were noted.
Addition of a thiopurine in patients who have lost response to anti-TNF monotherapy is an effective strategy to recapture response even if the patient has previously failed thiopurine therapy. Thiopurines may reduce immunogenicity or act synergistically with anti-TNF therapy.
抗肿瘤坏死因子（TNF）抗体在维持克罗恩病缓解方面非常有效。然而，随着时间的推移，相当一部分患者对这些药物失去了反应。本研究旨在确定在对 TNF 单药治疗失去反应的患者中引入硫嘌呤是否会导致再次应答。
5 名（男 4 例；年龄 22-38 岁）患有活动期克罗恩病的患者，他们对 TNF 治疗有初始反应，但已失去反应，开始给予标准剂量的硫唑嘌呤或巯基嘌呤，同时继续 TNF 治疗。所有患者在开始 TNF 治疗前均已对硫嘌呤治疗失败。
所有患者在 2-6 个月内临床症状均得到改善，平均随访 19 个月时仍持续获益。2 名在添加硫嘌呤时 C 反应蛋白升高的患者，C 反应蛋白下降。4 例患者在添加硫嘌呤前后行结肠镜检查，均显示所有患者均有改善，其中 2 例达到黏膜愈合。未观察到治疗的不良反应。
在对 TNF 单药治疗失去反应的患者中添加硫嘌呤是一种有效的策略，可以重新获得应答，即使患者之前对硫嘌呤治疗失败。硫嘌呤可能会降低免疫原性或与 TNF 治疗协同作用。
