Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease:: an open randomised trial
Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease:: an open randomised trial
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DOI：
10.1016/s0140-6736(08)60304-9
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发表时间：
2008-02-23
期刊：
影响因子：
168.9
通讯作者：
Hommes, Daniel
中科院分区：
文献类型：
--
作者：
D'Haens, Geert;Baert, Filip;Hommes, Daniel
大多数活动性克罗恩病患者最初接受皮质类固醇治疗。虽然这种方法通常可以控制症状，但许多患者对皮质类固醇产生耐药性或依赖性，长期暴露与死亡风险增加有关。我们的目的是比较早期使用联合免疫抑制与传统的管理活动性克罗恩病的患者谁以前没有收到糖皮质激素，抗代谢药，或infliximab.Methods的有效性，我们做了一个为期2年的开放标签随机试验，在18个中心在比利时，荷兰，和德国之间，2001年5月，2004年1月。我们将133例患者随机分为早期联合免疫抑制治疗组和常规治疗组。67名被分配接受联合免疫抑制的患者在第0周、第2周和第6周接受3次英夫利西单抗（5 mg/kg体重）输注以及硫唑嘌呤。我们给予英夫利西单抗和皮质类固醇（如有必要）额外治疗，以控制疾病活动。66例患者被分配到常规管理接受皮质类固醇，其次是硫唑嘌呤和英夫利昔单抗。主要结果指标是在第26周和第52周时缓解，未使用皮质类固醇，未进行肠切除。本试验注册于ClinicalTrials.gov，编号NCT 00554710。结果4例患者（每组2例）未按方案接受治疗。第26周，联合免疫抑制组65例患者中有39例（60.0%）在未使用皮质类固醇和未进行手术切除的情况下缓解，而对照组64例患者中有23例（35.9%）缓解，绝对差异为24.1%（95%CI 7.3-40.8，p=0.0062）。第52周的相应发生率为40/65（61.5%）和27/64（42.2%）（绝对差异19.3%，95% CI 2.4-36.3，p=0.0278）。早期联合免疫抑制组65例患者中有20例（30.8%）发生严重不良事件，而对照组64例患者中有19例（25.3%）发生严重不良事件（p=1.0）。解释联合免疫抑制比常规治疗更有效地诱导缓解和减少近期诊断为克罗恩病的患者使用皮质类固醇。在病程早期开始更强化的治疗可能会产生更好的结果。
Background Most patients who have active Crohn's disease are treated initially with corticosteroids. Although this approach usually controls symptoms, many patients become resistant to or dependent on corticosteroids, and long exposure is associated with an increased risk of mortality. We aimed to compare the effectiveness of early use of combined immunosuppression with conventional management in patients with active Crohn's disease who had not previously received glucocorticoids, antimetabolites, or infliximab.Methods We did a 2-year open-label randomised trial at 18 centres in Belgium, Holland, and Germany between May, 2001, and January, 2004. We randomly assigned 133 patients to either early combined immunosuppression or conventional treatment. The 67 patients assigned to combined immunosuppression received three infusions of infliximab (5 mg/kg of bodyweight) at weeks 0, 2, and 6, with azathioprine. We gave additional treatment with infliximab and, if necessary, corticosteroids, to control disease activity. 66 patients assigned to conventional management received corticosteroids, followed, in sequence, by azathioprine and infliximab. The primary outcome measures were remission without corticosteroids and without bowel resection at weeks 26 and 52. Analysis was by modified intention to treat. This trial was registered with ClinicalTrials.gov, number NCT00554710.Findings Four patients (two in each group) did not receive treatment as per protocol. At week 26, 39 (60.0%) of 65 patients in the combined immunosuppression group were in remission without corticosteroids and without surgical resection, compared with 23 (35.9%) of 64 controls, for an absolute difference of 24.1% (95% CI 7.3-40.8, p=0.0062). Corresponding rates at week 52 were 40/65 (61.5%) and 27/64 (42.2%) (absolute difference 19.3%, 95% CI 2.4-36.3, p=0.0278). 20 of the 65 patients (30.8%) in the early combined immunosuppression group had serious adverse events, compared with 19 of 64 (25.3%) controls (p=1.0).Interpretation Combined immunosuppression was more effective than conventional management for induction of remission and reduction of corticosteroid use in patients who had been recently diagnosed with Crohn's disease. Initiation of more intensive treatment early in the course of the disease could result in better outcomes.