阻断肿瘤坏死因子α在重症持续哮喘中的随机、双盲、安慰剂对照研究
2009/05/18
研究目的在于评估人源抗TNF-α单克隆抗体golimumab在大样本未控制的重症持续哮喘患者中的安全性和有效性。
309位患者随机分为4组：每月皮下注射安慰剂或golimumab（50、100和200 mg）共52周。结果显示，24周时各组FEV1占预计值百分比的变化和急性加重次数无显著性差异。2.6％的安慰剂组和19.5％的golimumab组患者未继续用药，各组分别有1.3％和7.8％的患者退出研究。76周时各组分别有20.5％和30.3％的患者发生严重不良事件，golimumab组更频繁地发生严重感染。golimumab组中有1名死亡，8名发生恶性疾病。
研究结果显示，对于重症哮喘持续患者，Golimumab治疗并未显示确切的疗效。
（熊亮 华中科技大学同济医学院附属协和医院呼吸科 430022 摘译）
（Am J Respir Crit Care Med. 2009; 179: 549-558）
（熊亮 华中科技大学同济医学院附属协和医院呼吸科 430022 摘译）
（Am J Respir Crit Care Med. 2009; 179: 549-558）
A Randomized, Double-blind, Placebo-controlled Study of Tumor Necrosis Factor-a Blockade in Severe Persistent Asthma
Rationale: The treatment effect of golimumab, a humanmonoclonal antibody against tumor necrosis factor (TNF)-a, in severe persistent asthma is unknown.
Objectives: To assess the safety and efficacy of golimumab in a large population of patients with uncontrolled, severe persistent asthma.
Methods: From 2004 to 2006, 309 patients with severe and un-controlled asthma, despite high-dose inhaled corticosteroids and long-acting b2 agonists, were randomized 1:1:1:1 to monthly sub-cutaneous injections of placebo or golimumab (50, 100, or 200 mg) through Week 52. Coprimary endpoints were the change from base-line through Week 24 in prebronchodilator percent-predicted FEV1 and the number of severe asthma exacerbations throughWeek 24. Measurements and Main Results: No significant differences were observed for the change in percent-predicted FEV1 (least squares mean: placebo, 2.44 [95% confidence interval (CI) 20.574 to 5.461]; combined 100-mg and 200-mg, 2.91 [0.696–5.116]) or severe exac-erbations (mean6SD: placebo, 0.561.07 vs. combined100-mgand 200-mg 0.5 6 0.97) through week 24. Through Week 24, 2.6% of patients treated with placebo vs. 19.5% of those treated with golimumab discontinued the study agent, and 1.3% and 7.8% dis-continued study participation, respectively. An unfavorable risk–benefit profile led to early discontinuation of study-agent adminis-tration after the Week-24 database lock. Through Week 76, 20.5%of patients treated with placebo and 30.3% of patients treated with golimumab experienced serious adverse events, with serious infections occurring more frequently in golimumab-treated patients. One death and all eight malignancies occurred in the active groups.
Conclusions: Overall, treatment with golimumab did not demonstrate a favorable risk–benefit profile in this study population of patientswith severe persistent asthma.
Methods: From 2004 to 2006, 309 patients with severe and un-controlled asthma, despite high-dose inhaled corticosteroids and long-acting b2 agonists, were randomized 1:1:1:1 to monthly sub-cutaneous injections of placebo or golimumab (50, 100, or 200 mg) through Week 52. Coprimary endpoints were the change from base-line through Week 24 in prebronchodilator percent-predicted FEV1 and the number of severe asthma exacerbations throughWeek 24. Measurements and Main Results: No significant differences were observed for the change in percent-predicted FEV1 (least squares mean: placebo, 2.44 [95% confidence interval (CI) 20.574 to 5.461]; combined 100-mg and 200-mg, 2.91 [0.696–5.116]) or severe exac-erbations (mean6SD: placebo, 0.561.07 vs. combined100-mgand 200-mg 0.5 6 0.97) through week 24. Through Week 24, 2.6% of patients treated with placebo vs. 19.5% of those treated with golimumab discontinued the study agent, and 1.3% and 7.8% dis-continued study participation, respectively. An unfavorable risk–benefit profile led to early discontinuation of study-agent adminis-tration after the Week-24 database lock. Through Week 76, 20.5%of patients treated with placebo and 30.3% of patients treated with golimumab experienced serious adverse events, with serious infections occurring more frequently in golimumab-treated patients. One death and all eight malignancies occurred in the active groups.
Conclusions: Overall, treatment with golimumab did not demonstrate a favorable risk–benefit profile in this study population of patientswith severe persistent asthma.
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