Exploring the Effects of Omalizumab in Allergic Asthma An Analysis of Biomarkers in the EXTRA Study
Exploring the Effects of Omalizumab in Allergic Asthma An Analysis of Biomarkers in the EXTRA Study
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DOI：
10.1164/rccm.201208-1414oc
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发表时间：
2013-04-15
影响因子：
24.7
通讯作者：
Busse, William
中科院分区：
文献类型：
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作者：
Hanania, Nicola A.;Wenzel, Sally;Busse, William
理由：对于许多哮喘患者，过敏性气道炎症主要是th2加权过程；然而，炎症模式的异质性表明存在影响疾病表现和治疗效果的表型差异。目的：评估分数呼出型一氧化氮（FENO）、外周血嗜酸粒细胞计数和血清骨膜蛋白作为Th2炎症的生物标志物和omalizumab治疗效果预测因子的潜力。方法：EXTRA omalizumab研究纳入了患有未控制的严重持续性过敏性哮喘的患者（年龄12 - 75岁）。分析评估治疗效果与基线时FENO、血嗜酸性粒细胞和血清骨膜蛋白的关系。患者被分为低和高生物标志物亚组。在48周的治疗期间（主要终点），以方案定义的哮喘加重次数来评估治疗效果。测量方法和主要结果：共纳入850例患者。分别从394例（46.4%）、797例（93.8%）和534例（62.8%）患者中获得FEN、血嗜酸性粒细胞和血清骨膜蛋白的数据。48周后，所有三种生物标志物的高亚组与低亚组相比，方案定义的加重减少更大：FEN， 53%（95%置信区间[CI]， 37-70, P = 0.001）对16% (95% CI, 32 - 46, P = 0.45)；嗜酸性粒细胞32% （95% CI, 11-48; P = 0.005）对9% (95% CI, -24 - 34; P = 0.54)；30% (95% CI, -2 ~ 51; P = 0.07) vs 3% （95% CI, -43 ~ 32; P = 0.94）。结论：在三个高生物标志物亚组中，omalizumab和安慰剂之间的恶化频率差异最大，可能与高亚组中更大的恶化风险相关。需要进一步的研究来探索这些生物标志物在临床实践中的价值。临床试验注册于www.clinicaltrials.gov （NCT00314574）。
Rationale: For many patients with asthma, allergic airway inflammation is primarily a Th2-weighted process; however, heterogeneity in patterns of inflammation suggests phenotypic distinctions exist that influence disease presentation and treatment effects. Objectives: To assess the potential of fractional exhaled nitric oxide (FENO), peripheral blood eosinophil count, and serum periostin as biomarkers of Th2 inflammation and predictors of treatment effects of omalizumab.Methods: The EXTRA omalizumab study enrolled patients (aged 12 75 yr) with uncontrolled severe persistent allergic asthma. Analyses were performed evaluating treatment effects in relation to FENO, blood eosinophils, and serum periostin at baseline. Patients were divided into low- and high-biomarker subgroups. Treatment effects were evaluated as number of protocol-defined asthma exacerbations during the 48-week treatment period (primary endpoint). Measurements and Main Results: A total of 850 patients were enrolled. Data were available from 394 (46.4%), 797 (93.8%), and 534(62.8%) patients for FEN, blood eosinophils, and serum periostin, respectively. After 48 weeks of omalizumab, reductions in protocol-defined exacerbations were greater in high versus low subgroups for all three biomarkers: FEN, 53% (95% confidence interval [CI], 37-70; P = 0.001) versus 16% (95% CI, 32 to 46; P = 0.45); eosinophils, 32% (95% CI, 11-48; P = 0.005) versus 9% (95% CI, -24 to 34; P = 0.54); and periostin, 30% (95% CI, -2 to 51; P = 0.07) versus 3% (95% CI, -43 to 32; P = 0.94).Conclusions: The difference in exacerbation frequency between omalizumab and placebo was greatest in the three high-biomarker subgroups, probably associated with the greater risk for exacerbations in high subgroups. Additional studies are required to explore the value of these biomarkers in clinical practice. Clinical trial registered with www.clinicaltrials.gov (NCT00314574).