The role of a soluble TNFα receptor fusion protein (etanercept) in corticosteroid refractory asthma:: a double blind, randomised, placebo controlled trial
The role of a soluble TNFα receptor fusion protein (etanercept) in corticosteroid refractory asthma:: a double blind, randomised, placebo controlled trial
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DOI：
10.1136/thx.2007.086314
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发表时间：
2008-07-01
期刊：
影响因子：
10
通讯作者：
Holgate, S. T.
中科院分区：
文献类型：
--
作者：
Morjaria, J. B.;Chauhan, A. J.;Holgate, S. T.
目的：肿瘤坏死因子α（TNF α）是一种细胞因子，被认为是慢性炎症性疾病的治疗靶点。方法：一项随机、双盲、安慰剂对照的平行组试验，报道了依那西普（IgG 1-TNF p75受体融合蛋白），每周一次，连续12周治疗39例严重皮质类固醇难治性哮喘患者。通过哮喘相关生活质量（AQLQ）和哮喘控制（ACQ）问卷评分（主要终点）、肺功能、呼气峰流速（PEF）和支气管高反应性（BHR）较治疗前基线的变化来衡量疗效。痰液和血清炎症细胞和细胞因子，血清白蛋白和C反应蛋白（CRP）作为炎症的生物标志物也进行了评估。治疗组和安慰剂组在ACQ评分的降低方面存在微小但显著的差异（分别为-1.11（95% CI -1.56至-0.75）和-0.52（95% CI -0.97至-0.07），p=0.037）。两组间AQLQ评分、肺功能、PEF、BHR或加重率的改善无显著差异。依那西普组的轻微不良事件，包括注射部位疼痛和皮疹更常见。有一个显着减少痰巨噬细胞和CRP，增加血清TNF α和白蛋白治疗后，但不是在其他实验室parameter.Conclusion：依那西普治疗超过12周表现出只有一个小的，但显着改善哮喘控制和全身炎症，血清白蛋白和CRP测定。需要更大规模的随机、安慰剂对照试验来阐明TNF α拮抗作用在重度难治性哮喘受试者中的作用。
Aim: Tumour necrosis factor alpha (TNF alpha) is a cytokine recognised as a therapeutic target in chronic inflammatory diseases.Methods: A randomised, double blind, placebo controlled parallel group trial is reported of etanercept (an IgG1-TNF p75 receptor fusion protein), administered once weekly for 12 weeks in 39 patients with severe corticosteroid refractory asthma. Efficacy was measured by change from the pretreatment baseline in Asthma Related Quality of Life (AQLQ) and Asthma Control (ACQ) Questionnaire scores (the primary endpoints), lung function, peak expiratory flow (PEF) and bronchial hyperresponsiveness (BHR). Sputum and serum inflammatory cells and cytokines, serum albumin and C reactive protein (CRP) as biomarkers of inflammation were also assessed.Results: There was a small but significant difference in reduction of ACQ scores between treatment and placebo (-1.11 (95% CI -1.56 to -0.75) and -0.52 (95% CI -0.97 to -0.07), respectively, p=0.037). There was no significant difference in improvements in AQLQ scores, lung function, PEF, BHR or exacerbation rates between the groups. Minor adverse events, including injection site pain and skin rashes, were more frequent with etanercept. There was a significant reduction in sputum macrophages and CRP, and increases in serum TNFa and albumin following treatment, but not in other laboratory parameters.Conclusion: Etanercept therapy over 12 weeks demonstrated only a small but significant improvement in asthma control and systemic inflammation, as measured by serum albumin and CRP. Larger randomised, placebo controlled trials are required to clarify the role of TNFa antagonism in subjects with severe refractory asthma.