Background: The anti-IgE monoclonal antibody omalizumab is widely used for severe asthma. This study aimed to identify biomarkers that predict clinical improvement during 1 year of omalizumab treatment. Methods: One-year open-label Study of Mechanisms of action of Omalizumab in Severe Asthma (SoMOSA) involving 216 patients with severe (Global Initiative for Asthma step 4/5) uncontrolled atopic asthma (at least two severe exacerbations in the previous year) taking high-dose inhaled corticosteroids and long-acting β-agonists with or without maintenance oral corticosteroids. It had two phases: 0-16 weeks, to assess early clinical improvement by Global Evaluation of Therapeutic Effectiveness (GETE); and 16-52 weeks, to assess late responses based on ⩾50% reduction in exacerbations or mOCS dose. All participants provided samples (exhaled breath, blood, sputum, urine) before and after 16 weeks of omalizumab treatment. Measurements and Main Results: A total of 191 patients completed phase 1; 63% had early improvement. Of 173 who completed phase 2, 69% had reduced exacerbations by ⩾50% and 57% (37 of 65) taking mOCSs had reduced their dose by ⩾50%. The primary outcomes 2,3-dinor-11-β-PGF2α, GETE score, and standard clinical biomarkers (blood and sputum eosinophils, exhaled nitric oxide, serum IgE) did not predict either clinical response. Five volatile organic compounds and five plasma lipid biomarkers strongly predicted the ⩾50% reduction in exacerbations (receiver operating characteristic areas under the curve of 0.780 and 0.922, respectively) and early responses (areas under the curve of 0.835 and 0.949, respectively). In an independent cohort, gas chromatography/mass spectrometry biomarkers differentiated between severe and mild asthma. Conclusions: This is the first discovery of omics biomarkers that predict improvement in asthma with biologic agent treatment. Prospective validation and development for clinical use is justified.

中文翻译：

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抗 IgE 生物制剂奥马珠单抗治疗成人严重哮喘临床疗效的生物标志物预测因素：SoMOSA 研究结果。


背景：抗IgE单克隆抗体奥马珠单抗广泛用于治疗严重哮喘。本研究旨在确定可预测奥马珠单抗治疗一年期间临床改善的生物标志物。方法：为期一年的奥马珠单抗治疗严重哮喘作用机制的开放标签研究 (SoMOSA)，涉及 216 名患有严重（全球哮喘倡议第 4/5 步）不受控制的特应性哮喘患者（前一年至少有两次严重恶化）服用大剂量吸入性皮质类固醇和长效β受体激动剂，联合或不联合维持口服皮质类固醇。它分为两个阶段：0-16周，通过治疗效果全球评估（GETE）评估早期临床改善； 16-52 周，根据恶化或 mOCS 剂量减少 50% 来评估晚期反应。所有参与者在奥马珠单抗治疗 16 周之前和之后都提供了样本（呼出气、血液、痰液、尿液）。测量和主要结果：共有 191 名患者完成了第 1 阶段； 63% 的人有早期改善。在完成第 2 阶段的 173 名患者中，69% 的患者病情加重减少了 50%，57%（65 名患者中的 37 名）服用 mOCS 后剂量减少了 50%。主要结局 2,3-dinor-11-β-PGF2α、GETE 评分和标准临床生物标志物（血液和痰嗜酸性粒细胞、呼出一氧化氮、血清 IgE）均不能预测任何临床反应。五种挥发性有机化合物和五种血浆脂质生物标志物强烈预测恶化（曲线下的接收者操作特征面积分别为 0.780 和 0.922）和早期反应（曲线下的面积分别为 0.835 和 0.949）将减少 50%。在一个独立的队列中，气相色谱/质谱生物标志物区分了重度和轻度哮喘。 结论：这是预测生物制剂治疗哮喘改善的组学生物标志物的首次发现。临床应用的前瞻性验证和开发是合理的。