Kawalec Paweł, Moćko Paweł, Malinowska-Lipien Iwona, Brzostek Tomasz
Drug Management Department, Institute of Public Health, Faculty of Health Sciences, Jagiellonian University Medical College, Kraków, Poland.
Department of Internal & Community Nursing, Institute of Nursing & Midwifery, Faculty of Health Sciences, Jagiellonian University Medical College, Kraków, Poland.
J Comp Eff Res. 2017 Oct;6(7):601-612. doi: 10.2217/cer-2017-0022. Epub 2017 Jun 29.
The aim of the systematic review and meta-analysis was to assess the efficacy and safety of ustekinumab in the induction therapy of anti-TNF-α failure patients with Crohn's disease.
A systematic literature search was conducted in Medline (PubMed), EMBASE, Cochrane Library until 30 December 2016. We included randomized controlled trials that compared efficacy (clinical response and remission) and safety profile of ustekinumab in TNF-α failure Crohn's disease patients; primary and secondary TNF-α nonresponders or intolerant patients were also assessed. Included studies were critically appraised according to the PRISMA statement protocol; data aggregation with a RevMan software was performed.
Three randomized controlled trials were revealed in the systematic review but only two of them (CERTIFI and UNITI-1) were homogenous to be included in the meta-analysis; aggregation of data only for induction phase of therapy was possible. Clinical response was significantly higher for patients who received ustekinumab compared with placebo patients in a group of TNF-α antagonist failure patients (relative benefit [RB] = 1.62; 95% CI: 1.28-2.04) and in the following subgroups: secondary nonresponders (RB = 1.98; 95% CI: 1.49-2.63), intolerant patients (RB = 1.47; 95% CI: 1.01-2.13) and patients who failed at least two TNF-α antagonists (RB = 2.19; 95% CI: 1.53-3.14) but in case of primary nonresponders it occurred insignificant (RB = 1.22; 95% CI: 0.76-1.98). The clinical remission in TNF-α antagonist failure population was significantly higher for patients who received ustekinumab compared with placebo (RB = 1.72; 95% CI: 1.17-2.53). Pooled analysis revealed that risk of adverse events in induction phase of therapy was not significantly different (risk ratio = 0.96; 95% CI: 0.86-1.06) between ustekinumab and placebo groups.
The clinical response was significantly higher for TNF-α antagonist failure patients who received ustekinumab as well as in subgroups of secondary nonresponders or intolerant patients but not in case of primary nonresponders. Ustekinumab occurred as safe as placebo in the induction as well as in a maintenance phase of therapy.
本系统评价和荟萃分析的目的是评估优特克单抗在抗TNF-α治疗失败的克罗恩病患者诱导治疗中的疗效和安全性。
截至2016年12月30日，在Medline（PubMed）、EMBASE、Cochrane图书馆进行了系统的文献检索。我们纳入了比较优特克单抗在TNF-α治疗失败的克罗恩病患者中的疗效（临床反应和缓解）及安全性的随机对照试验；还评估了原发性和继发性TNF-α无反应者或不耐受患者。根据PRISMA声明方案对纳入的研究进行严格评价；使用RevMan软件进行数据汇总。
系统评价中发现了三项随机对照试验，但其中只有两项（CERTIFI和UNITI-1）同质，可纳入荟萃分析；仅对治疗诱导期的数据进行汇总。在一组TNF-α拮抗剂治疗失败的患者中，接受优特克单抗治疗的患者的临床反应显著高于接受安慰剂治疗的患者（相对获益[RB]=1.62；95%置信区间：1.28-2.04），在以下亚组中也是如此：继发性无反应者（RB=1.98；95%置信区间：1.49-2.63）、不耐受患者（RB=1.47；95%置信区间：1.01-2.13）以及至少两种TNF-α拮抗剂治疗失败的患者（RB=2.19；95%置信区间：1.53-3.14），但在原发性无反应者中差异不显著（RB=1.22；95%置信区间：0.76-1.98）。在TNF-α拮抗剂治疗失败的人群中，接受优特克单抗治疗的患者的临床缓解率显著高于接受安慰剂治疗的患者（RB=1.72；95%置信区间：1.17-至2.53）。汇总分析显示，优特克单抗组和安慰剂组在治疗诱导期不良事件风险无显著差异（风险比=0.96；95%置信区间：0.86-1.06）。
接受优特克单抗治疗的TNF-α拮抗剂治疗失败患者以及继发性无反应者或不耐受患者亚组的临床反应显著更高，但原发性无反应者并非如此。在治疗诱导期和维持期，优特克单抗与安慰剂一样安全。
