Kips Johan C, O'Connor Brian J, Langley Stephen J, Woodcock Ashley, Kerstjens Huib A M, Postma Dirkje S, Danzig Mel, Cuss Francis, Pauwels Romain A
Department of Respiratory Diseases, Ghent University Hospital, De Pintelaan 185, B 9000 Ghent, Belgium.
Am J Respir Crit Care Med. 2003 Jun 15;167(12):1655-9. doi: 10.1164/rccm.200206-525OC. Epub 2003 Mar 20.
Antagonizing the effect of interleukin (IL)-5 is a potential new treatment strategy in allergic disorders. We evaluated the safety, biological activity, and pharmacokinetics of SCH55700, a humanized anti-human IL-5 antibody, in subjects with severe persistent asthma treated with oral or high doses of inhaled steroids. In a double-blind, randomized, multicenter trial, a rising single dose of SCH55700 (0.03 mg/kg [n = 2], 0.1 mg/kg [n = 4], 0.3 mg/kg [n = 6], or 1.0 mg/kg [n = 12]) or placebo (n = 8) was administered intravenously. SCH55700 dose dependently reduced circulating eosinophil counts. At a dose of 1.0 mg/kg, the decrease remained significant up to Day 30 [(0.07 +/- 0.01) x 10(9)/L versus (0.23 +/- 0.04) x 10(9)/L at baseline] (mean +/- SEM) (p = 0.05). After administration of SCH55700 at 0.3 and 1.0 mg/kg, a trend toward improvement in baseline FEV1 was observed, which reached significance 24 hours after the 0.3-mg/kg dose (p = 0.019 versus placebo). No significant changes occurred in other clinical indices of disease activity. Adverse events were not different between active treatment and placebo. We conclude that SCH55700 is a biologically active anti-human IL-5 antibody that can be safely used in severe steroid-treated asthma. Its therapeutic potential needs to be addressed in specifically designed efficacy trials.
拮抗白细胞介素(IL)-5的作用是治疗过敏性疾病的一种潜在新策略。我们评估了人源化抗人IL-5抗体SCH55700在接受口服或高剂量吸入性类固醇治疗的重度持续性哮喘患者中的安全性、生物活性和药代动力学。在一项双盲、随机、多中心试验中,静脉注射递增单剂量的SCH55700(0.03mg/kg [n = 2]、0.1mg/kg [n = 4]、0.3mg/kg [n = 6]或1.0mg/kg [n = 12])或安慰剂(n = 8)。SCH55700剂量依赖性地降低循环嗜酸性粒细胞计数。在1.0mg/kg剂量时,直至第30天下降仍显著[(0.07±0.01)×10⁹/L 对比基线时的(0.23±0.04)×10⁹/L](均值±标准误)(p = 0.05)。在给予0.3mg/kg和1.0mg/kg的SCH55700后,观察到基线第一秒用力呼气容积(FEV1)有改善趋势,在0.3mg/kg剂量后24小时达到显著水平(与安慰剂相比p = 0.019)。疾病活动的其他临床指标未发生显著变化。活性治疗组和安慰剂组的不良事件无差异。我们得出结论,SCH55700是一种具有生物活性的抗人IL-5抗体,可安全用于重度类固醇治疗的哮喘。其治疗潜力需要在专门设计的疗效试验中加以探讨。