Abstract：
OBJECTIVE: Approximately 40% of patients with steroid-refractory acute severe ulcerative colitis (steroid-refractory (SR) ASUC) requires colectomies. Advanced therapies may reduce the short-term colectomy rates in patients with SR ASUC. However, comparative clinical studies evaluating the effectiveness of these rescue therapies are lacking. Therefore, we conducted a network meta-analysis to study the effectiveness of rescue therapies for SR ASUC.
METHODS: Six randomized controlled trials and 15 cohort studies including 2,004 patients were analyzed. Rescue drugs included tofacitinib, infliximab with a 5 or 10 mg/kg induction dose at 0, 2, and 6 weeks (IFX and IFX10, respectively), IFX with an accelerated regimen of three 5 mg/kg induction doses timed according to clinical need (accelerated IFX), tacrolimus, cyclosporine (CyA), ustekinumab, and adalimumab. Treatments were compared with a placebo.
RESULTS: Tofacitinib (odds ratio [OR]: 0.09 [95% confidence interval [CI]: 0.02-0.52]), accelerated IFX (OR: 0.16 [95% CI: 0.03-0.94]), IFX (OR: 0.2 [95% CI: 0.07-0.58]), and tacrolimus (OR: 0.24 [95% CI: 0.06-0.96]) significantly reduced the short-term colectomy rates compared with placebo. IFX10 and CyA tended to prevent colectomies. However, ustekinumab and adalimumab did not significantly affect the colectomy rates.
CONCLUSIONS: This is the first network meta-analysis to investigate the efficacy of advanced therapies in reducing short-term colectomy rates in patients with SR ASUC. Tofacitinib, accelerated IFX, standard IFX, and tacrolimus significantly reduced the colectomy rates in SR ASUC patients compared with placebo. Thus, advanced therapies should be considered for rescue therapies in patients with SR ASUC.
METHODS: Six randomized controlled trials and 15 cohort studies including 2,004 patients were analyzed. Rescue drugs included tofacitinib, infliximab with a 5 or 10 mg/kg induction dose at 0, 2, and 6 weeks (IFX and IFX10, respectively), IFX with an accelerated regimen of three 5 mg/kg induction doses timed according to clinical need (accelerated IFX), tacrolimus, cyclosporine (CyA), ustekinumab, and adalimumab. Treatments were compared with a placebo.
RESULTS: Tofacitinib (odds ratio [OR]: 0.09 [95% confidence interval [CI]: 0.02-0.52]), accelerated IFX (OR: 0.16 [95% CI: 0.03-0.94]), IFX (OR: 0.2 [95% CI: 0.07-0.58]), and tacrolimus (OR: 0.24 [95% CI: 0.06-0.96]) significantly reduced the short-term colectomy rates compared with placebo. IFX10 and CyA tended to prevent colectomies. However, ustekinumab and adalimumab did not significantly affect the colectomy rates.
CONCLUSIONS: This is the first network meta-analysis to investigate the efficacy of advanced therapies in reducing short-term colectomy rates in patients with SR ASUC. Tofacitinib, accelerated IFX, standard IFX, and tacrolimus significantly reduced the colectomy rates in SR ASUC patients compared with placebo. Thus, advanced therapies should be considered for rescue therapies in patients with SR ASUC.
摘要：
目的：大约40%的激素难治性急性重度溃疡性结肠炎（激素难治性（SR）ASUC）患者需要结肠切除术。先进的治疗可能会降低SRASUC患者的短期结肠切除术率。然而,缺乏评估这些抢救疗法有效性的比较临床研究.因此,我们进行了一项网络荟萃分析,以研究SRASUC的抢救疗法的有效性.
方法：分析了6项随机对照试验和15项队列研究，包括2,004例患者。救援药物包括托法替尼，在0、2和6周时使用5或10mg/kg诱导剂量的英夫利昔单抗（分别为IFX和IFX10），IFX采用根据临床需要定时的三个5mg/kg诱导剂量的加速方案（加速IFX），他克莫司,环孢菌素(CyA),ustekinumab,和阿达木单抗.将治疗与安慰剂进行比较。
结果：托法替尼（优势比[OR]：0.09[95％置信区间[CI]：0.02-0.52]），加速IFX(OR：0.16[95%CI：0.03-0.94])，IFX（OR：0.2[95%CI：0.07-0.58]），与安慰剂相比,他克莫司(OR:0.24[95%CI:0.06-0.96])显著降低短期结肠切除术率.IFX10和CyA倾向于预防结肠切除术。然而,ustekinumab和阿达木单抗对结肠切除术率无显著影响.
结论：这是第一个网络荟萃分析，旨在研究先进疗法在降低SRASUC患者短期结肠切除率方面的疗效。托法替尼,加速IFX，标准IFX，与安慰剂相比，他克莫司显著降低了SRASUC患者的结肠切除术率。因此，SRASUC患者的抢救治疗应考虑采用先进疗法.
方法：分析了6项随机对照试验和15项队列研究，包括2,004例患者。救援药物包括托法替尼，在0、2和6周时使用5或10mg/kg诱导剂量的英夫利昔单抗（分别为IFX和IFX10），IFX采用根据临床需要定时的三个5mg/kg诱导剂量的加速方案（加速IFX），他克莫司,环孢菌素(CyA),ustekinumab,和阿达木单抗.将治疗与安慰剂进行比较。
结果：托法替尼（优势比[OR]：0.09[95％置信区间[CI]：0.02-0.52]），加速IFX(OR：0.16[95%CI：0.03-0.94])，IFX（OR：0.2[95%CI：0.07-0.58]），与安慰剂相比,他克莫司(OR:0.24[95%CI:0.06-0.96])显著降低短期结肠切除术率.IFX10和CyA倾向于预防结肠切除术。然而,ustekinumab和阿达木单抗对结肠切除术率无显著影响.
结论：这是第一个网络荟萃分析，旨在研究先进疗法在降低SRASUC患者短期结肠切除率方面的疗效。托法替尼,加速IFX，标准IFX，与安慰剂相比，他克莫司显著降低了SRASUC患者的结肠切除术率。因此，SRASUC患者的抢救治疗应考虑采用先进疗法.
