Stack W A, Mann S D, Roy A J, Heath P, Sopwith M, Freeman J, Holmes G, Long R, Forbes A, Kamm M A
Division of Gastroenterology, University Hospital, Nottingham, UK.
Lancet. 1997 Feb 22;349(9051):521-4. doi: 10.1016/s0140-6736(97)80083-9.
Tumour necrosis factor-alpha (TNF alpha) is thought to have a central role in the pathogenesis of Crohn's disease. We tested the hypothesis that CDP571, a genetically engineered human antibody to TNF alpha, is effective in modifying disease activity in patients with moderately active Crohn's disease.
In this double-blind, placebo-controlled study, 31 patients were randomly assigned to CDP571 (n = 21) or placebo (n = 10). The primary endpoint was change in Crohn's disease activity index 2 weeks after a single infusion of CDP571 (5 mg/kg), or human albumin as placebo. One patient who attended no follow-up assessments was excluded from the analyses (CDP571 group).
The median Crohn's disease activity index fell from 263 (IQR 186.5-323.5) at baseline to 167 (137.5-294.0) at 2 weeks in the CDP571-treated patients (p = 0.0003); the change in the placebo group (253 [240-334] to 247 [183-256]) was not significant. In the treated group, there were also significant differences between baseline and 2 weeks in Harvey-Bradshaw score (p = 0.0005), key symptom score (p = 0.049), alpha 1-glycoprotein concentration (p = 0.012), and erythrocyte sedimentation rate (p = 0.01); concentrations of C-reactive protein fell, but not significantly (p = 0.067). Six patients achieved remission (Crohn's disease activity index < or = 150) and three others had activity indices of 156 or lower. There were no significant changes in the placebo group.
A single 5 mg/kg infusion of CDP571 reduced disease activity in Crohn's disease at 2 weeks. These data suggest that antibody neutralisation of TNF alpha is a potentially effective strategy in the management of Crohn's disease. The use of CDP571 in Crohn's disease requires further study.
肿瘤坏死因子-α（TNFα）被认为在克罗恩病的发病机制中起核心作用。我们检验了如下假设：CDP571，一种基因工程改造的抗TNFα人源抗体，可有效改善中度活动期克罗恩病患者的疾病活动度。
在这项双盲、安慰剂对照研究中，31例患者被随机分配至CDP571组（n = 21）或安慰剂组（n = 10）。主要终点为单次输注CDP571（5 mg/kg）或人白蛋白作为安慰剂2周后克罗恩病活动指数的变化。1例未参加随访评估的患者被排除在分析之外（CDP571组）。
CDP571治疗的患者中，克罗恩病活动指数的中位数从基线时的263（四分位间距186.5 - 323.5）降至2周时的167（137.5 - 294.0）（p = 0.0003）；安慰剂组的变化（从253 [240 - 334]至247 [183 - 256]）无统计学意义。在治疗组中，Harvey - Bradshaw评分（p = 0.0005）、关键症状评分（p = 0.049）、α1 - 糖蛋白浓度（p = 0.012）和红细胞沉降率（p = 0.01）在基线和2周之间也存在显著差异；C反应蛋白浓度下降，但无统计学意义（p = 0.067）。6例患者达到缓解（克罗恩病活动指数≤150），另外3例患者的活动指数为156或更低。安慰剂组无显著变化。
单次输注5 mg/kg的CDP571可在2周时降低克罗恩病的疾病活动度。这些数据表明，抗体中和TNFα是治疗克罗恩病的一种潜在有效策略。CDP571在克罗恩病中的应用需要进一步研究。
