Martín De Carpi J, Varea V
Sección de Gastroenterología, Hepatología y Nutrición Pediátrica, Hospital Sant Joan de Déu, Universidad de Barcelona, Esplugues de Llobregat, Barcelona, España.
An Pediatr (Barc). 2009 Mar;70(3):271-7. doi: 10.1016/j.anpedi.2008.09.014. Epub 2008 Nov 28.
The use of immunomodulatory agents has changed the management of inflammatory bowel disease. Immunosuppressive drugs (mainly thiopurines) and biological treatments (mainly monoclonal antibodies against TNFalpha) are currently most frequently and earlier used. The recent report of new cases of the rare and almost always fatal hepatosplenic T-cell lymphoma in young patients on combined therapy with azathioprine/6-mercaptopurine and infliximab suggests that the optimal strategies for reducing increased risk of side-effects need to be urgently assessed.
We report the effects of stopping immunosupressants in four Crohn's disease patients previously treated with azathioprine and infliximab for 6-12 months as combined therapy. The appearance of infusion reactions due to immunogenicity and the loss of efficacy of infliximab are evaluated.
No adverse events attributable to immunosuppression cessation or changes in infliximab efficacy have been noted during a 6-month evaluation period.
Stopping immunosuppressant therapy in Crohn's patients with a previous good response to combination therapy (azathioprine and infliximab) does not result in an increased risk of adverse events or loss of infliximab efficacy. Our results must be confirmed in larger and longer studies. Until the pathogenic role of this combined therapy in the incidence of hepatosplenic T-cell lymphoma is clearly defined, we consider that monotherapy with infliximab after a period on combined treatment is a safe and effective strategy.
免疫调节剂的使用改变了炎症性肠病的治疗方式。免疫抑制药物（主要是硫唑嘌呤）和生物治疗（主要是抗TNFα单克隆抗体）目前使用最为频繁且使用时间更早。近期有报告称，在接受硫唑嘌呤/6-巯基嘌呤与英夫利昔单抗联合治疗的年轻患者中出现了罕见且几乎总是致命的肝脾T细胞淋巴瘤新病例，这表明迫切需要评估降低副作用风险增加的最佳策略。
我们报告了4例克罗恩病患者停用免疫抑制剂的效果，这些患者此前接受硫唑嘌呤和英夫利昔单抗联合治疗6至12个月。评估了因免疫原性导致的输注反应的出现情况以及英夫利昔单抗疗效的丧失情况。
在6个月的评估期内，未观察到因停用免疫抑制剂或英夫利昔单抗疗效改变而导致的不良事件。
对于此前联合治疗（硫唑嘌呤和英夫利昔单抗）反应良好的克罗恩病患者，停用免疫抑制治疗不会增加不良事件风险或导致英夫利昔单抗疗效丧失。我们的结果必须在更大规模、更长时间的研究中得到证实。在这种联合治疗在肝脾T细胞淋巴瘤发病率中的致病作用明确之前，我们认为在联合治疗一段时间后采用英夫利昔单抗单药治疗是一种安全有效的策略。
