在严重哮喘中滴定抗IL5生物制剂（OPTIMAL）：一项开放标签随机对照试验
2024/07/30
摘要
背景：抗白细胞介素5（抗IL5）生物制剂可有效减少严重嗜酸性粒细胞哮喘的急性加重和维持口服糖皮质激素（mOCS）的需要。然而，抗IL5治疗应持续多久尚不清楚。来自临床试验的数据表明，在停止治疗后，患者病情逐渐失控，但存在个体间差异。在这项滴定的初步研究中，本研究在应用抗IL5生物制剂控制病情的患者中评估剂量滴定算法。
方法：本项开放标签随机对照试验历时52周，将接受抗IL5治疗的临床对照（无急性发作或应用mOCS）患者随机分为以继续固定间隔治疗，或根据滴定算法调整给药间隔——即逐渐延长给药间隔并在出现疾病失控迹象时再次缩短给药间隔。OPTIMAL算法旨在降低滴定剂量，直到出现失控迹象，从而能够评估可能的最长给药间隔。
结果：本研究纳入的73名患者中，37名被随机分配到OPTIMAL滴定组，78%的患者可耐受降级滴定治疗。与对照组相比，OPTIMAL组在研究期间的病情加重程度更高（32% vs 17%（p=0.013））。无与药物滴定相关的严重不良事件发生。两研究组的肺功能和症状评分始终保持稳定且相当。
结论：本研究为重症哮喘患者的抗IL5生物制剂滴定提供了概念验证，并对治疗进行临床控制。OPTIMAL算法为未来个性化给药间隔提供了潜在方案。
OPTIMAL: Titration of anti-IL5 biologics in severe asthma - An open label randomised controlled trial.
Soendergaard MB, Bjerrum AS, Rasmussen LM, Lock-Johansson S, Hilberg O, Hansen S, von Bulow A, Porsbjerg C.
Abstract
BACKGROUND:Anti-interleukin 5 (anti-IL5) biologics effectively reduce exacerbations and the need for maintenance oral corticosteroids (mOCS) in severe eosinophilic asthma. However, it is unknown how long anti-IL5 treatment should be continued. Data from clinical trials indicate a gradual but variable loss of control after treatment cessation. In this pilot study of titration, we evaluated a dose-titration algorithm in patients who had achieved clinical control on an anti-IL5 biologic.
METHODS:In this open-label randomised controlled trial conducted over 52 weeks, patients with clinical control (no exacerbations or mOCS) on anti-IL5 treatment were randomised to continue with unchanged intervals or have dosing intervals adjusted according to a titration algorithm that gradually extended dosing intervals and reduced them again at signs of loss of disease control. The OPTIMAL algorithm was designed to down-titrate dosing until signs of loss of control, to enable assessment of the longest dosing interval possible.
RESULTS:Among 73 patients enrolled, 37 patients were randomised to the OPTIMAL titration arm; 78% of patients tolerated down-titration of treatment. Compared to the control arm, the OPTIMAL arm tended to have more exacerbations during the study (32% versus 17% (p=0.13)). There were no severe adverse events related to titration, and lung function and symptoms scores remained stable and comparable in both study arms throughout.
CONCLUSION:This study serves as a proof-of-concept for titration of anti-IL5 biologics in patients with severe asthma with clinical control on treatment, and the OPTIMAL algorithm provides a potential framework for individualising dosing intervals in the future.
背景：抗白细胞介素5（抗IL5）生物制剂可有效减少严重嗜酸性粒细胞哮喘的急性加重和维持口服糖皮质激素（mOCS）的需要。然而，抗IL5治疗应持续多久尚不清楚。来自临床试验的数据表明，在停止治疗后，患者病情逐渐失控，但存在个体间差异。在这项滴定的初步研究中，本研究在应用抗IL5生物制剂控制病情的患者中评估剂量滴定算法。
方法：本项开放标签随机对照试验历时52周，将接受抗IL5治疗的临床对照（无急性发作或应用mOCS）患者随机分为以继续固定间隔治疗，或根据滴定算法调整给药间隔——即逐渐延长给药间隔并在出现疾病失控迹象时再次缩短给药间隔。OPTIMAL算法旨在降低滴定剂量，直到出现失控迹象，从而能够评估可能的最长给药间隔。
结果：本研究纳入的73名患者中，37名被随机分配到OPTIMAL滴定组，78%的患者可耐受降级滴定治疗。与对照组相比，OPTIMAL组在研究期间的病情加重程度更高（32% vs 17%（p=0.013））。无与药物滴定相关的严重不良事件发生。两研究组的肺功能和症状评分始终保持稳定且相当。
结论：本研究为重症哮喘患者的抗IL5生物制剂滴定提供了概念验证，并对治疗进行临床控制。OPTIMAL算法为未来个性化给药间隔提供了潜在方案。
(中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校)
(Eur Respir J. 2024 Jun 6:2400404. doi: 10.1183/13993003.00404-2024. Epub ahead of print.)
(Eur Respir J. 2024 Jun 6:2400404. doi: 10.1183/13993003.00404-2024. Epub ahead of print.)
OPTIMAL: Titration of anti-IL5 biologics in severe asthma - An open label randomised controlled trial.
Soendergaard MB, Bjerrum AS, Rasmussen LM, Lock-Johansson S, Hilberg O, Hansen S, von Bulow A, Porsbjerg C.
Abstract
BACKGROUND:Anti-interleukin 5 (anti-IL5) biologics effectively reduce exacerbations and the need for maintenance oral corticosteroids (mOCS) in severe eosinophilic asthma. However, it is unknown how long anti-IL5 treatment should be continued. Data from clinical trials indicate a gradual but variable loss of control after treatment cessation. In this pilot study of titration, we evaluated a dose-titration algorithm in patients who had achieved clinical control on an anti-IL5 biologic.
METHODS:In this open-label randomised controlled trial conducted over 52 weeks, patients with clinical control (no exacerbations or mOCS) on anti-IL5 treatment were randomised to continue with unchanged intervals or have dosing intervals adjusted according to a titration algorithm that gradually extended dosing intervals and reduced them again at signs of loss of disease control. The OPTIMAL algorithm was designed to down-titrate dosing until signs of loss of control, to enable assessment of the longest dosing interval possible.
RESULTS:Among 73 patients enrolled, 37 patients were randomised to the OPTIMAL titration arm; 78% of patients tolerated down-titration of treatment. Compared to the control arm, the OPTIMAL arm tended to have more exacerbations during the study (32% versus 17% (p=0.13)). There were no severe adverse events related to titration, and lung function and symptoms scores remained stable and comparable in both study arms throughout.
CONCLUSION:This study serves as a proof-of-concept for titration of anti-IL5 biologics in patients with severe asthma with clinical control on treatment, and the OPTIMAL algorithm provides a potential framework for individualising dosing intervals in the future.
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