严重哮喘的靶向治疗:实际临床实践中生物制剂的转换--原因与后果

V. Naumova, E. Beltyukov, D. Kiseleva, G. А. Bykova, O. Smolenskaya, A. А. Shtanova, D. А. Stepina
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引用次数: 0

摘要

背景:选择基因工程生物药物(GEBD)治疗严重支气管哮喘(SA)的复杂性在于疾病的内型和表型的交叉。生物药物选择的失误会导致治疗效果不佳而停药和/或换药。 目的:在实际临床实践中确定哮喘患者停止靶向治疗的原因和生物制剂转换的有效性。 材料与方法:分析斯维尔德洛夫斯克地区登记的 SA 患者(n=116),并将其分为 3 组(#1-持续组、#2-停药组和#3-换药组)。确定了停用和更换生物制剂的预测因素、首次停用生物制剂的原因、更换方案、更换后的治疗效果(根据ACT、FEV1、AQLQ、SNOT-22、SGCS的需求、SA缓解的实现情况)。 结果:在登记的 116 名患者中,17.2% 的患者停药,12.1% 的患者换药。停药患者患 CRSwNP 的频率较低,哮喘发病时间较早。换药患者的血液嗜酸性粒细胞水平较高。45%的患者因个人原因取消治疗。对 SA 和/或 CRSwNP 治疗无效是换药的主要原因(92.8%),其中大部分患者换药时使用的是奥马珠单抗和苯拉利珠单抗。转换药物的首选是杜比鲁单抗。改善指标:ACT(提高了86.4%)、FEV1(提高了21.2%)、AQLQ(提高了52.5%)、SNOT-22(提高了48%)。62.5%的患者(不包括 FEV1)和 50%的患者(包括 FEV1)获得了缓解。 结论:谨慎选择靶向治疗患者可将起始药物的失败率降至 12.1%。将仅用于阻断嗜酸性粒细胞或仅用于阻断 IgE 的起始 GEBD 转换为具有双重作用机制的药物,可显著改善 ACT、FEV1、AQLQ、SNOT-22 的疗效,且无需使用 SGCS。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Targeted Therapy of Severe Asthma: Switching of Biologicals in Real Clinical Practice – Causes and Consequences
BACKGROUND: complexity of choice a genetically engineered biological drug (GEBD) for severe bronchial asthma (SA) treatment is due to intersection of endotypes and phenotypes of the disease. Mistakes in biologicals choice lead to discontinuation and/or switching of the drug due to insufficient effectiveness of therapy. AIMS: to determine reasons to stop targeted therapy and biologicals switching effectiveness in patients with SA in real clinical practice. MATERIALS AND METHODS: analyzed patients with SA (n=116) from Sverdlovsk region register were divided into 3 groups (#1-continuous, #2-stoppers and #3-switched). Predictors of biologicals withdrawal and switching, reasons for the 1st biological stopping, switching schemes, therapy effectiveness after switching (according to ACT, FEV1, AQLQ, SNOT-22, the need for SGCS, achievement of SA remission) were determined. RESULTS: There were 17.2% stopping and 12.1% switching patients out of 116 patients in the registry. Stoppers suffered from CRSwNP less often and had earlier asthma onsets. Switched patients had higher blood eosinophils level. Therapy was cancelled for personal reasons in 45% of patients. Therapys ineffectiveness in SA and/or in CRSwNP was the main reason for switching (92.8%) mostly from omalizumab and benralizumab. The switch drug of choice was dupilumab. Improved indicators: ACT (by 86.4%), FEV1 (by 21.2%), AQLQ (by 52.5%), SNOT-22 (by 48%), the need for SGCS decreased to 0 in 12 months after switching. Remission was achieved in 62.5% of patients (excluding FEV1) and 50% of patients (including FEV1). CONCLUSIONS: Careful selection of targeted therapy patients allows to minimize the failures of the starting drug to 12.1%. Switching the starting GEBD, aimed only at blocking eosinophils or only at blocking IgE, due to its inefficiency, to a drug with a dual mechanism of action leads to a significant improvement in ACT, FEV1, AQLQ, SNOT-22 and absence of SGCS need.
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