一种新型聚乙二醇化人源化抗TNF片段（CDP870）治疗类风湿关节炎患者的疗效：一项II期双盲、随机、剂量递增试验。
Efficacy of a novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid arthritis: a phase II double-blinded, randomized, dose-escalating trial.
作者信息
Choy E H S, Hazleman B, Smith M, Moss K, Lisi L, Scott D G I, Patel J, Sopwith M, Isenberg D A
机构信息
Academic Department of Rheumatology, GKT School of Medicine, King's College London, King's College Hospital, London, UK.
出版信息
Rheumatology (Oxford). 2002 Oct;41(10):1133-7. doi: 10.1093/rheumatology/41.10.1133.
OBJECTIVE
Biological products that neutralize tumour necrosis factor alpha (TNF-alpha) are beneficial in rheumatoid arthritis (RA). We studied the effects of CDP870, a novel anti-TNF-alpha antibody fragment modified to obtain a prolonged plasma half-life ( approximately 14 days).
METHODS
Thirty-six patients were randomized in a double-blind, ascending-dose group study to a single intravenous infusion of placebo (n = 12) or 1, 5 or 20 mg/kg CDP870 (each n = 8). The patients were predominantly female (30/36), had a mean age of 56 yr and a mean duration of RA of 13 years. They had received a mean of five DMARDs or experimental therapies (with 1 month washout before the study started) and had active disease. Continuation of NSAIDs and up to 7.5 mg prednisolone daily was allowed. Following the blinded dosing period, 32 patients received a single open-label infusion of either 5 or 20 mg/kg CDP870.
RESULTS
In the blinded dosing period, 6/12 placebo patients withdrew from the study (for deteriorating RA < or =4 weeks after dosing). Two of 24 CDP870-treated patients withdrew, both in the 1 mg/kg group (for deteriorating RA or lost to follow up >4 weeks after dosing). The proportion of patients with ACR20 improvement for the per-protocol population with the last observation carried forward was 16.7, 50, 87.5 and 62.5% after 0, 1, 5 and 20 mg/kg CDP870 respectively (combined treatment effect, P = 0.012, primary analysis) at 4 weeks and 16.7, 25, 75 and 75% (P = 0.032) at 8 weeks. The proportion of patients with ACR50 improvement for the per-protocol population with the last observation carried forward was 0, 12.5, 12.5 and 50% after 0, 1, 5 and 20 mg/kg CDP870 respectively (combined treatment effect, P = 0.079) at 4 weeks and 0, 12.5, 12.5 and 50% (P = 0.079) at 8 weeks. Following the open-label dose of CDP870, similar beneficial effects were achieved.
CONCLUSION
CDP870 is effective, was very well tolerated in this small study, and has an extended duration of action following one or more intravenous doses.
目的
中和肿瘤坏死因子α（TNF-α）的生物制品对类风湿关节炎（RA）有益。我们研究了CDP870的效果，它是一种新型抗TNF-α抗体片段，经修饰后血浆半衰期延长（约14天）。
方法
36例患者被随机分为双盲、递增剂量组研究，接受单次静脉输注安慰剂（n = 12）或1、5或20 mg/kg CDP870（每组n = 8）。患者以女性为主（30/36），平均年龄56岁，RA平均病程13年。他们平均接受过5种改善病情抗风湿药（DMARDs）或实验性治疗（研究开始前有1个月的洗脱期）且疾病处于活动期。允许继续使用非甾体抗炎药（NSAIDs），每日泼尼松龙剂量最高可达7.5 mg。在盲法给药期后，32例患者接受单次开放标签输注5或20 mg/kg CDP870。
结果
在盲法给药期，12例安慰剂患者中有6例退出研究（给药后≤4周RA病情恶化）。24例接受CDP870治疗的患者中有2例退出，均在1 mg/kg组（给药后RA病情恶化或失访>4周）。在4周时，对于采用末次观察值结转的符合方案人群，接受0、1、5和20 mg/kg CDP870治疗后达到美国风湿病学会（ACR）20改善标准的患者比例分别为16.7%、50%、87.5%和62.5%（联合治疗效果，P = 0.012，初步分析），8周时分别为16.
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