Swansea University Medical School, Swansea, UK.
College of Human and Health Sciences, Swansea University, Swansea, UK.
Lancet Gastroenterol Hepatol. 2016 Sep;1(1):15-24. doi: 10.1016/S2468-1253(16)30003-6.
Infliximab and ciclosporin are of similar efficacy in treating acute severe ulcerative colitis, but there has been no comparative evaluation of their relative clinical effectiveness and cost-effectiveness.
In this mixed methods, open-label, pragmatic randomised trial, we recruited consenting patients aged 18 years or older at 52 district general and teaching hospitals in England, Scotland, and Wales who had been admitted, unscheduled, with severe ulcerative colitis and failed to respond to intravenous hydrocortisone within about 5 days. Patients were randomly allocated (1:1) to receive either infliximab (5 mg/kg intravenous infusion given over 2 h at baseline, and again at 2 weeks and 6 weeks after the first infusion) or ciclosporin (2 mg/kg per day by continuous infusion for up to 7 days, followed by twice-daily tablets delivering 5·5 mg/kg per day for 12 weeks). Randomisation used a web-based password-protected site, with a dynamic algorithm to generate allocations on request, thus protecting against investigator preference or other subversion, while ensuring that each trial group was balanced by centre, which was the only stratification used. Local investigators and participants were aware of the treatment allocated, but the chief investigator and analysts were masked. Analysis was by treatment allocated. The primary outcome was quality-adjusted survival-ie, the area under the curve (AUC) of scores from the Crohn's and Ulcerative Colitis Questionnaire (CUCQ) completed by participants at baseline, 3 months, and 6 months, then every 6 months from 1 year to 3 years. This trial is registered with the ISRCTN Registry, number ISRCTN22663589.
Between June 17, 2010, and Feb 26, 2013, 270 patients were recruited. 135 patients were allocated to the infliximab group and 135 to the ciclosporin group. 121 (90%) patients in each group were included in the analysis of the primary outcome. There was no significant difference between groups in quality-adjusted survival (mean AUC 564·0 [SD 241·9] in the infliximab group 587·0 [226·2] in the ciclosporin group; mean adjusted difference 7·9 [95% CI -22·0 to 37·8]; p=0·603). Likewise, there were no significant differences between groups in the secondary outcomes of CUCQ scores, EQ-5D, or SF-6D scores; frequency of colectomy (55 [41%] of 135 patients in the infliximab group 65 [48%] of 135 patients in the ciclosporin group; p=0·223); or mean time to colectomy (811 [95% CI 707-912] days in the infliximab group 744 [638-850] days in the ciclosporin group; p=0·251). There were no differences in serious adverse reactions (16 reactions in 14 participants receiving infliximab ten in nine patients receiving ciclosporin); serious adverse events (21 in 16 patients 25 in 17 patients); or deaths (three in the infliximab group none in the ciclosporin group).
There was no significant difference between ciclosporin and infliximab in clinical effectiveness.
NIHR Health Technology Assessment programme.
英夫利昔单抗和环孢素在治疗急性重度溃疡性结肠炎方面疗效相似，但尚未对其相对临床疗效和成本效益进行比较评估。
在这项混合方法、开放标签、实用随机试验中，我们在英格兰、苏格兰和威尔士的 52 家地区综合医院和教学医院招募了年龄在 18 岁及以上、因重度溃疡性结肠炎而未经计划入院且对大约 5 天内静脉注射氢化可的松无反应的患者。患者以 1:1 的比例随机分配（1:1）接受英夫利昔单抗（在基线时给予 5mg/kg 的静脉输注，在第一次输注后 2 周和 6 周再次给予）或环孢素（2mg/kg/天持续输注，最长 7 天，然后每天两次给予 5.5mg/kg 的片剂，持续 12 周）。随机分配使用基于网络的密码保护网站，使用动态算法根据请求生成分配，从而防止调查人员的偏好或其他颠覆，同时确保每个试验组通过中心平衡，这是唯一使用的分层。当地调查人员和参与者了解分配的治疗方案，但首席调查人员和分析人员被蒙在鼓里。分析是按治疗方案进行的。主要结局是质量调整生存，即参与者在基线、3 个月和 6 个月时使用克罗恩病和溃疡性结肠炎问卷（CUCQ）完成的评分的曲线下面积（AUC），然后从 1 年到 3 年，每 6 个月评估一次。这项试验在 ISRCTN 注册中心注册，编号为 ISRCTN22663589。
在 2010 年 6 月 17 日至 2013 年 2 月 26 日期间，共招募了 270 名患者。135 名患者被分配到英夫利昔单抗组，135 名患者被分配到环孢素组。每组各有 121 名（90%）患者纳入主要结局分析。两组在质量调整生存方面没有显著差异（英夫利昔单抗组平均 AUC 为 564.0[241.9]，环孢素组为 587.0[226.2]；平均调整差异为 7.9[95%CI-22.0 至 37.8]；p=0.603）。同样，两组在 CUCQ 评分、EQ-5D 和 SF-6D 评分、结肠切除术的频率（英夫利昔单抗组 55[41%]名患者 环孢素组 65[48%]名患者；p=0.223）或结肠切除术的平均时间（英夫利昔单抗组 811[95%CI707-912]天 环孢素组 744[638-850]天；p=0.251）方面也没有显著差异。两组严重不良反应（英夫利昔单抗组 14 名患者中有 16 次反应 环孢素组 9 名患者中有 10 次反应）；严重不良事件（英夫利昔单抗组 16 名患者中有 21 次 环孢素组 17 名患者中有 25 次）；或死亡（英夫利昔单抗组 3 例 环孢素组无）。
在临床疗效方面，环孢素和英夫利昔单抗之间没有显著差异。
英国国家卫生与临床优化研究所健康技术评估计划。
