Hamada Yuto, Gibson Peter G, Harvey Erin S, Stevens Sean, Lewthwaite Hayley, Fricker Michael, McDonald Vanessa M, Gillman Andrew, Hew Mark, Kritikos Vicky, Upham John W, Thomas Dennis
Center of Excellence in Treatable Traits, College of Health, Medicine and Wellbeing, University of Newcastle, New Lambton Heights, New South Wales, Australia; Asthma and Breathing Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia; Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan.
Center of Excellence in Treatable Traits, College of Health, Medicine and Wellbeing, University of Newcastle, New Lambton Heights, New South Wales, Australia; Asthma and Breathing Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia; Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, New South Wales, Australia.
J Allergy Clin Immunol Pract. 2025 Feb;13(2):333-342.e9. doi: 10.1016/j.jaip.2024.10.041. Epub 2024 Nov 6.
Mepolizumab can induce an early response and clinical remission in people with severe eosinophilic asthma (SEA).
To find whether early response to mepolizumab (100 mg) could predict future asthma remission and to identify the best predictor of treatment response to mepolizumab for achieving remission.
The Australian Mepolizumab Registry was used to investigate the early response to mepolizumab at 3 and 6 months and relate this to clinical remission at 12 months. Treatment response was assessed using the 5-item Asthma Control Questionnaire (ACQ-5), oral corticosteroid (OCS) dose, exacerbation frequency, and postbronchodilator FEV. Clinical remission, assessed at 12 months, was defined as an ACQ-5 score less than or equal to 1.0 at 12 months, no exacerbations in the previous 6 months, and no OCS use for asthma in the previous 6 months. We estimated the optimism-corrected area under the curve for internal validation.
We analyzed 255 participants with SEA. Seventy-eight (30.6%) participants achieved clinical remission at 12 months. A prediction model including ACQ-5 score, exacerbation frequency, OCS dose, and postbronchodilator FEV at 6 months was more predictive of achieving remission than measures at 3 months. The ACQ-5 score at 6 months had the highest optimism-corrected area under the curve of 0.778 (95% CI, 0.719-0.833). An ACQ-5 score less than 1.5 at 6 months had a sensitivity of 85.9% for achieving clinical remission, whereas an ACQ-5 score less than 0.75 had a specificity of 84.7%.
The ACQ-5 score at 6 months was the best predictor of achieving clinical remission at 12 months in people with SEA treated with mepolizumab. These results can be used to design a treat-to-target paradigm for asthma, in which treatment response is assessed at 6 months to predict clinical remission.
美泊利单抗可诱导重度嗜酸性粒细胞性哮喘(SEA)患者出现早期反应并实现临床缓解。
探究对美泊利单抗(100毫克)的早期反应是否能够预测未来的哮喘缓解情况,并确定实现缓解的美泊利单抗治疗反应的最佳预测指标。
利用澳大利亚美泊利单抗注册研究来调查在3个月和6个月时对美泊利单抗的早期反应,并将其与12个月时的临床缓解情况相关联。使用5项哮喘控制问卷(ACQ-5)、口服糖皮质激素(OCS)剂量、加重频率和支气管扩张剂后第一秒用力呼气容积(FEV)来评估治疗反应。在12个月时评估的临床缓解定义为12个月时ACQ-5评分小于或等于1.0、前6个月无加重发作且前6个月未使用OCS治疗哮喘。我们估计了用于内部验证的曲线下面积的乐观校正值。
我们分析了255例SEA患者。78例(30.6%)患者在12个月时实现了临床缓解。与3个月时的指标相比,一个包含6个月时ACQ-5评分、加重频率、OCS剂量和支气管扩张剂后FEV的预测模型对实现缓解的预测性更强。6个月时的ACQ-5评分具有最高的乐观校正曲线下面积,为0.778(95%可信区间,0.719 - 0.833)。6个月时ACQ-5评分小于1.5对实现临床缓解的敏感性为85.9%,而ACQ-5评分小于0.75的特异性为84.7%。
在接受美泊利单抗治疗的SEA患者中,6个月时的ACQ-5评分是12个月时实现临床缓解的最佳预测指标。这些结果可用于设计哮喘的靶向治疗模式,即在6个月时评估治疗反应以预测临床缓解。