Efficacy of a novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid arthritis: a phase II double-blinded, randomized, dose-escalating trial
Efficacy of a novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid arthritis: a phase II double-blinded, randomized, dose-escalating trial
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DOI：
10.1093/rheumatology/41.10.1133
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发表时间：
2002-10-01
期刊：
影响因子：
5.5
通讯作者：
Isenberg, DA
中科院分区：
文献类型：
--
作者：
Choy, EHS;Hazleman, B;Isenberg, DA
客观的。中和肿瘤坏死因子 α (TNF-α) 的生物制品对类风湿性关节炎 (RA) 有益。我们研究了 CDP870 的影响，CDP870 是一种新型抗 TNF-α 抗体片段，经过修饰以获得延长的血浆半衰期（类似于 14 天）。方法。在一项双盲、剂量递增组研究中，36 名患者被随机分配接受单次静脉输注安慰剂 (n = 12) 或 1、5 或 20 mg/kg CDP870（各 n = 8）。患者主要为女性 (30/36)，平均年龄为 56 岁，平均 RA 持续时间为 13 年。他们平均接受了 5 种 DMARD 或实验疗法（研究开始前 1 个月清除）并且患有活动性疾病。允许继续使用 NSAID 和每天最多 7.5 mg 的泼尼松龙。在盲法给药期后，32 名患者接受了单次开放标签输注 5 或 20 mg/kg CDP870。 结果。在盲法给药期间，6/12 名安慰剂患者退出研究（因给药后 RA 恶化小于或等于 4 周）。 24 名接受 CDP870 治疗的患者中有 2 名退出，均为 1 mg/kg 组（因 RA 恶化或给药后 4 周以上失访）。 0、1、5和20 mg/kg CDP870治疗后，按方案人群中ACR20改善的患者比例（合并最后一次观察）在4周时分别为16.7、50、87.5和62.5%（综合治疗效果，P = 0.012，初步分析），在4周时为16.7、25、75和75%（P = 0.032）8周时。 0、1、5 和 20 mg/kg CDP870 治疗后 4 周时，按方案人群 ACR50 改善的患者比例与最后一次观察结果分别为 0、12.5、12.5 和 50%（综合治疗效果，P = 0.079）；4 周时，ACR50 改善的患者比例为 0、12.5、12.5 和 50%（P = 0.079）。 8周。 CDP870 的开放标签剂量后，取得了类似的有益效果。结论。 CDP870 有效，在这项小型研究中具有良好的耐受性，并且在一次或多次静脉注射后具有延长的作用持续时间。
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 (similar to 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 less than or equal to 4 weeks after dosing). Two of 24 CDP870-treated patients withdrew, both in the I 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.