Szemes Kata, Soós Alexandra, Hegyi Péter, Farkas Nelli, Erős Adrienn, Erőss Bálint, Mezősi Emese, Szakács Zsolt, Márta Katalin, Sarlós Patrícia
First Department of Medicine, Medical School, University of Pécs, Pécs, Hungary.
Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.
Front Med (Lausanne). 2020 Jan 21;6:338. doi: 10.3389/fmed.2019.00338. eCollection 2019.
In steroid-refractory acute severe ulcerative colitis (ASUC), cyclosporine (CYS) or infliximab (IFX) may be considered as a second-line alternative to avoid colectomy. There are short-term data reported, but until now, there is no meta-analysis regarding long-term outcomes of CYS and IFX in patients with ASUC. To compare long-term efficacy and safety of CYS and IFX in a meta-analysis. Three electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials) were searched for studies which compared CYS vs. IFX in adults with ASUC. Long-term colectomy-free rate from 1 to 10 years during CYS or IFX therapy was collected, last updated up to 22nd May 2019. Primary outcome was long-term colectomy-free rate, secondary outcomes were adverse events (AE), serious adverse events (SAE), and mortality. Long-term colectomy-free survival and safety measures were pooled with the random-effect model. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. Data from 1,607 patients in 15 trials were extracted. In the first 3 years, pooled OR for colectomy-free survival was higher with IFX than with CYS (OR = 1.59, 95% CI: 1.11-2.29, = 0.012; OR = 1.57, 95% CI: 1.14-2.18, = 0.006; and OR = 1.75, 95% CI: 1.08-2.84, = 0.024; at 1, 2, and 3 years, respectively). However, the significant difference remained undetected from the fourth year of follow-up and in subgroup of RCTs (OR = 1.35, 95% CI: 0.90-2.01, = 0.143; OR = 1.41, 95% CI: 0.94-2.12, = 0.096; and OR = 1.34, 95% CI: 0.89-2.00, = 0.157; at 1, 2, and 3 years, respectively). No significant difference was detected regarding adverse events, serious adverse events and mortality between the groups. The neutral associations proved to be underpowered with trial sequential analysis. However observational studies show IFX as a better choice, according to the RCTs, choosing either CYS or IFX as rescue therapy for ASUC, the long-term outcomes are not different, although further large RCTs are warranted.
在类固醇难治性急性重症溃疡性结肠炎（ASUC）中，环孢素（CYS）或英夫利昔单抗（IFX）可被视为避免结肠切除术的二线替代方案。有短期数据报道，但截至目前，尚无关于CYS和IFX治疗ASUC患者长期结局的荟萃分析。为在荟萃分析中比较CYS和IFX的长期疗效和安全性。检索了三个电子数据库（PubMed、Embase、Cochrane对照试验中央注册库），以查找比较CYS与IFX治疗成年ASUC患者的研究。收集了CYS或IFX治疗期间1至10年的长期无结肠切除率，最后更新至2019年5月22日。主要结局是长期无结肠切除率，次要结局是不良事件（AE）、严重不良事件（SAE）和死亡率。采用随机效应模型汇总长期无结肠切除生存率和安全指标。计算95%置信区间（CI）的比值比（OR）。提取了15项试验中1607例患者的数据。在最初3年，IFX治疗的无结肠切除生存率合并OR高于CYS（分别在第1、2和3年，OR = 1.59，95% CI：1.11 - 2.29，P = 0.012；OR = 1.57，95% CI：1.14 - 2.18，P = 0.006；OR = 1.75，95% CI：1.08 - 2.84，P = 0.024）。然而，从随访第4年起及在随机对照试验亚组中未发现显著差异（分别在第1、2和3年，OR = 1.35，95% CI：0.90 - 2.01，P = 0.143；OR = 1.41，95% CI：0.94 - 2.12，P = 0.096；OR = 1.34，95% CI：0.89 - 2.00，P = 0.157）。两组之间在不良事件、严重不良事件和死亡率方面未发现显著差异。试验序贯分析表明中性关联的检验效能不足。然而，观察性研究显示IFX是更好的选择，根据随机对照试验，对于ASUC选择CYS或IFX作为挽救治疗，长期结局并无差异，尽管仍需要进一步的大型随机对照试验。
