抗TSLP抗体Tezepelumab治疗哮喘的临床研究现状
2022/12/21
摘要
胸腺基质淋巴生成素（TSLP）是一种上皮细胞衍生的细胞因子，通过先天性和后天性免疫级联在诱导2型炎症中发挥重要作用。Tezepelumab是一种抑制TSLP与TSLP受体结合的人IgG2单克隆抗体，是治疗哮喘的最新生物制剂。为了评估tezepelumab治疗哮喘的疗效和机制，进行了PATHWAY、NAVIGATOR、NOZOMI、UPSTREAM、CASCADE、SOURCE和DESTINATION等研究。这些结果表明，tezepelumab是一种广泛的靶向生物制剂，无论其表型如何，都有望对控制不良的中重度哮喘患者有效，尽管其对口服皮质类固醇依赖性哮喘的疗效、非2型表型的生物学机制和长期安全性尚不清楚。在这篇综述中，我们总结了tezepelumab治疗哮喘的临床试验结果，并讨论了tezepelumab与其他生物制剂之间的差异。
Current summary of clinical studies on anti-TSLP antibody, Tezepelumab, in asthma
Momoko Kurihara, Hiroki Kabata, Misato Irie, Koichi Fukunaga
Abstract
Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that plays a vital role in the induction of type 2 inflammation via both innate and acquired immune cascades. Tezepelumab, a human IgG2 monoclonal antibody that inhibits the binding of TSLP to the TSLP receptor, is the latest biologic for asthma. To evaluate the efficacy and mechanism of tezepelumab in asthma, the PATHWAY, NAVIGATOR, NOZOMI, UPSTREAM, CASCADE, SOURCE, and DESTINATION studies have been conducted. These results suggested that tezepelumab is a broad-target biologic, which is expected to be effective in patients with poorly controlled moderate to severe asthma regardless of the phenotype, although its efficacy in oral corticosteroids-dependent asthma, biological mechanism in non-type 2 phenotype, and long-term safety remain unknown. In this review, we summarize the results of clinical trials of tezepelumab in asthma and discuss the differences between tezepelumab and other biologics.
胸腺基质淋巴生成素（TSLP）是一种上皮细胞衍生的细胞因子，通过先天性和后天性免疫级联在诱导2型炎症中发挥重要作用。Tezepelumab是一种抑制TSLP与TSLP受体结合的人IgG2单克隆抗体，是治疗哮喘的最新生物制剂。为了评估tezepelumab治疗哮喘的疗效和机制，进行了PATHWAY、NAVIGATOR、NOZOMI、UPSTREAM、CASCADE、SOURCE和DESTINATION等研究。这些结果表明，tezepelumab是一种广泛的靶向生物制剂，无论其表型如何，都有望对控制不良的中重度哮喘患者有效，尽管其对口服皮质类固醇依赖性哮喘的疗效、非2型表型的生物学机制和长期安全性尚不清楚。在这篇综述中，我们总结了tezepelumab治疗哮喘的临床试验结果，并讨论了tezepelumab与其他生物制剂之间的差异。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Allergol Int. 2022 Dec 2;S1323-8930(22)00131-9. doi: 10.1016/j.alit.2022.11.006.)
(Allergol Int. 2022 Dec 2;S1323-8930(22)00131-9. doi: 10.1016/j.alit.2022.11.006.)
Current summary of clinical studies on anti-TSLP antibody, Tezepelumab, in asthma
Momoko Kurihara, Hiroki Kabata, Misato Irie, Koichi Fukunaga
Abstract
Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that plays a vital role in the induction of type 2 inflammation via both innate and acquired immune cascades. Tezepelumab, a human IgG2 monoclonal antibody that inhibits the binding of TSLP to the TSLP receptor, is the latest biologic for asthma. To evaluate the efficacy and mechanism of tezepelumab in asthma, the PATHWAY, NAVIGATOR, NOZOMI, UPSTREAM, CASCADE, SOURCE, and DESTINATION studies have been conducted. These results suggested that tezepelumab is a broad-target biologic, which is expected to be effective in patients with poorly controlled moderate to severe asthma regardless of the phenotype, although its efficacy in oral corticosteroids-dependent asthma, biological mechanism in non-type 2 phenotype, and long-term safety remain unknown. In this review, we summarize the results of clinical trials of tezepelumab in asthma and discuss the differences between tezepelumab and other biologics.
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一项T2-复合生物标志物策略调节严重哮喘皮质类固醇治疗的随机试验，按性别进行事后分析
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哮喘患者增加大剂量吸入皮质类固醇的效果：英国数据库研究
