IL-4变体对哮喘患者变应原导致的迟发哮喘反应的作用
2008/02/05
过敏性哮喘患者Th 2细胞因子浓度增加，IL-4及IL-13参与变应原引起的生理反应。Pitrakinra是一种IL-4的变体，可以通过阻断IL-4，IL-13与IL-4α受体复合物的结合从而阻断变应性Th2炎症反应。两项独立的2期随机对照双盲试验比较了2种途径应用pitrakinra对过敏性哮喘的治疗作用。第一项研究中，受试者每日皮下注射25 mg pitrakinra (n=12)或安慰剂1次(n=12)，主要研究终点为变应原刺激4～10小时后FEV1下降的最大百分比，随访期无患者脱落；在第二项研究中，受试者经压缩空气吸入60 mg pitrakinra (n=16)或安慰剂(n=16)每日2次，主要研究终点为变应原刺激4～10小时后FEV1下降的平均百分比，随访期2名安慰剂组患者和1名pitrakinra组患者脱落。第一项研究中，pitrakinra组FEV1下降的最大百分比为17.1%，而安慰剂组为23.1% (95% CI -4.37 to 16.32; p=0.243)。第二项研究中，pitrakinra组FEV1下降的平均百分比为4.4%，而安慰剂组为15.9% （95% CI 2.08-6.25；p=0.069)。皮下注射pitrakinra组需要β受体激动剂急救的不良事件发生率低于安慰剂组(p=0.031)。第二项研究中不良事件发生率很低，两组间无法进行比较。
这两项研究表明局部应用药物阻断肺内IL-4，IL-13的作用可缓解哮喘的症状。
（马艳良 北京大学人民医院呼吸科 100044 摘译）
(Lancet. 2007;370:1422-1431)
(Lancet. 2007;370:1422-1431)
Effect of an interleukin-4 variant on late phase asthmatic response to allergen
challenge in asthmatic patients: results of two phase 2a studies.
Wenzel S, Wilbraham D, Fuller R, Getz EB, Longphre M.
University of Pittsburgh, Division of Pulmonary, Allergy, and Critical Care
Medicine, Pittsburgh, PA, USA.
BACKGROUND: Increases in T helper (Th) 2 cytokine concentrations have been seen in atopic asthma, with interleukin 4 and interleukin 13 thought to have a role in the physiological response to allergen challenge. Our aim was to assess the therapeutic effect of pitrakinra, an interleukin-4 variant that targets allergic Th2 inflammation by potently inhibiting the binding of interleukin 4 and interleukin 13 to interleukin-4Ralpha receptor complexes.
METHODS: In two independent randomised, double-blind, placebo-controlled, parallel group phase 2aclinical trials, patients with atopic asthma were treated with pitrakinra or placebo via two routes. In study 1, patients were randomly assigned to receive either 25 mg pitrakinra (n=12) or placebo (n=12) by subcutaneous injection once daily. In study 2, patients were randomly assigned to receive either 60 mg pitrakinra (n=16) or placebo (n=16) by nebulisation twice daily. Inhaled allergen challenge was done before and after 4 weeks of treatment. The primary endpoint for study 1 was maximum percentage decrease in forced expiratory volume in 1 s (FEV1) over 4-10 h after allergen challenge, whereas that in study 2 was average percentage decrease in FEV(1) over 4-10 h after allergen challenge. All patients except those with baseline data only were included in our analyses. These trials are registered with ClinicalTrials.gov, numbers NCT00535028 and NCT00535031.
FINDINGS: No patients dropped out or were lost to follow-up in study 1; in study 2, two patients in the placebo group and one in the pitrakinra group dropped out or were lost to follow-up. These individuals had baseline data only, and were excluded from the analyses. In study 1, there was a 17.1% maximum percentage decrease in FEV1 in the pitrakinra group; by contrast, the maximum decrease was 23.1% in the placebo group (difference 6%, 95% CI -4.37 to 16.32; p=0.243). In study 2, there was a 4.4% average percentage decrease in FEV1 in the pitrakinra group; by contrast, the average percentage decrease was 15.9% in the placebo group (3.7 [95% CI 2.08-6.25] times lower in the pitrakinra group; p=0.0001). There were fewer asthma-related adverse events (p=0.069) and fewer adverse events requiring beta-agonist rescue (p=0.031) after subcutaneous administration of pitrakinra than with placebo. There were too few asthma-related adverse events in study 2 to assess the effect of inhalation of pitrakinra on adverse events.
INTERPRETATION: Local treatment, targeted at inhibition of interleukins 4 and 13 in the lung, could substantially diminish the symptoms of asthma.
上一篇：
哮喘患者外周T淋巴细胞蛋白质组分析
下一篇：
β2受体多态性和哮喘表型：与被动吸烟的关系
