Top-down infliximab plus azathioprine versus azathioprine alone in patients with acute severe ulcerative colitis responsive to intravenous steroids: a parallel, open-label randomised controlled trial, the ACTIVE trial.

Methods

We conducted a multicentre, parallel-group, open-label randomised controlled trialamong 23 French centres in thiopurine and biologics-naïve adults admitted for ASUC responding to intravenous steroids.

我们在23个法国中心进行了一项多中心、平行组、开放标签的随机对照试验，研究对象为接受静脉类固醇治疗后对急性重症溃疡性结肠炎（ASUC）发作有反应的硫唑嘌呤和生物制剂未经治疗的成人。

Eligible patients were randomly assigned to receive infliximab (IFX) and azathioprine (AZA) with a 7-day steroid tapering scheme (IFX+AZA arm) or AZA and conventional standardised steroid tapering regimen (AZA arm).

符合条件的患者被随机分配接受英夫利昔单抗（IFX）和硫唑嘌呤（AZA）以及7天的类固醇逐渐减量方案（IFX+AZA组），或AZA和常规标准化的类固醇逐渐减量方案（AZA组）。

The primary composite endpoint was treatment failure at week 52, defined as the absence of steroid-free clinical remission, the absence of endoscopic response, the use of a prohibited treatment for relapse, severe adverse eventleading to treatment interruption, colectomy or death.

主要复合终点是第52周的治疗失败，定义为缺乏无类固醇的临床缓解，缺乏内镜反应，使用禁忌的复发治疗药物，严重不良事件导致治疗中断，结肠切除术或死亡。

Multiple imputation for missing data was performed.

对缺失数据进行了多重插补处理。

Results

Among the 64 patients randomised (Lichtiger score 13.5±2.0; median age of 34.5 (P25-P75 26.3-50.3) years, median C reactive protein of 29.0 (12.8-96.8) mg/L at baseline): 32 were assigned to the IFX+AZA arm and 32 to the AZA arm.

在随机分配的64名患者中（Lichtiger评分13.5±2.0；基线时中位年龄为34.5（P25-P75 26.3-50.3）岁，中位C反应蛋白为29.0（12.8-96.8）mg/L）：32名患者被分配到IFX+AZA组，另外32名患者被分配到AZA组。

In the ITT population, treatment failure at week 52 was observed in 22/27 (81.5%) in the AZA arm and 16/30 (53.3%) in the IFX+AZA arm (risk ratio 3.85, 95% CI (1.15 to 12.88), p=0.03). 29 adverse events were severe, including 13 disease exacerbations, 6 severe infections without any difference between both arms.

在意向性治疗人群中，第52周时，AZA组27人中有22人（81.5%）出现治疗失败，而IFX+AZA组30人中有16人（53.3%）出现治疗失败（风险比3.85，95%置信区间（1.15至12.88），p=0.03）。共有29起严重不良事件，包括13起疾病加重和6起严重感染，两组之间没有差异。

interpretation

Combination therapy with IFX+AZA was more effective at 1 year than AZA alone to avoid treatment failure in patients with ASUC responding to intravenous steroids.

与单独使用AZA相比，IFX+AZA联合治疗在1年内对避免治疗失败更为有效，适用于对静脉注射类固醇有反应的ASUC患者。

trial_registration_number

NCT02425852.

NCT02425852。