Wenzel Sally E, Barnes Peter J, Bleecker Eugene R, Bousquet Jean, Busse William, Dahlén Sven-Erik, Holgate Stephen T, Meyers Deborah A, Rabe Klaus F, Antczak Adam, Baker James, Horvath Ildiko, Mark Zsuzsanna, Bernstein David, Kerwin Edward, Schlenker-Herceg Rozsa, Lo Kim Hung, Watt Rosemary, Barnathan Elliot S, Chanez Pascal
Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
Am J Respir Crit Care Med. 2009 Apr 1;179(7):549-58. doi: 10.1164/rccm.200809-1512OC. Epub 2009 Jan 8.
The treatment effect of golimumab, a human monoclonal antibody against tumor necrosis factor (TNF)-alpha, in severe persistent asthma is unknown.
To assess the safety and efficacy of golimumab in a large population of patients with uncontrolled, severe persistent asthma.
From 2004 to 2006, 309 patients with severe and uncontrolled asthma, despite high-dose inhaled corticosteroids and long-acting beta(2) agonists, were randomized 1:1:1:1 to monthly subcutaneous injections of placebo or golimumab (50, 100, or 200 mg) through Week 52. Coprimary endpoints were the change from baseline through Week 24 in prebronchodilator percent-predicted FEV(1) and the number of severe asthma exacerbations through Week 24.
No significant differences were observed for the change in percent-predicted FEV1 (least squares mean: placebo, 2.44 [95% confidence interval (CI) -0.574 to 5.461]; combined 100-mg and 200-mg, 2.91 [0.696-5.116]) or severe exacerbations (mean +/- SD: placebo, 0.5 +/- 1.07 vs. combined 100-mg and 200-mg 0.5 +/- 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% discontinued study participation, respectively. An unfavorable risk-benefit profile led to early discontinuation of study-agent administration 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.
Overall, treatment with golimumab did not demonstrate a favorable risk-benefit profile in this study population of patients with severe persistent asthma. Clinical trial registered with www.clinicaltrials.gov (NCT00207740).
抗肿瘤坏死因子（TNF）-α人源单克隆抗体戈利木单抗在重度持续性哮喘中的治疗效果尚不清楚。
评估戈利木单抗在大量未得到控制的重度持续性哮喘患者中的安全性和疗效。
2004年至2006年，309例尽管使用了高剂量吸入性糖皮质激素和长效β2受体激动剂但哮喘仍严重且未得到控制的患者，按1:1:1:1随机分组，接受每月一次皮下注射安慰剂或戈利木单抗（50、100或200毫克），持续至第52周。共同主要终点为支气管扩张剂使用前FEV1预测值百分比从基线至第24周的变化以及至第24周重度哮喘发作的次数。
在第24周时，预测FEV1百分比的变化（最小二乘均值：安慰剂组为2.44[95%置信区间（CI）-0.574至5.461]；100毫克和200毫克联合组为2.91[0.696 - 5.116]）或重度发作次数（均值±标准差：安慰剂组为0.5±1.07，100毫克和200毫克联合组为0.5±0.97）均未观察到显著差异。至第24周，接受安慰剂治疗的患者中有2.6%与接受戈利木单抗治疗的患者中有19.5%停止使用研究药物，分别有1.3%和7.8%停止参与研究。在第24周数据库锁定后，由于风险效益比不佳导致提前停止研究药物给药。至第76周，接受安慰剂治疗的患者中有20.5%以及接受戈利木单抗治疗的患者中有30.3%发生严重不良事件，严重感染在接受戈利木单抗治疗的患者中更频繁发生。1例死亡以及所有8例恶性肿瘤均发生在活性药物组。
总体而言，在该重度持续性哮喘患者研究人群中，戈利木单抗治疗未显示出良好的风险效益比。临床试验已在www.clinicaltrials.gov注册（NCT00207740）。
