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重度难治性哮喘建模:从健康状态转变

Modeling severe uncontrolled asthma: Transitioning away from health states.

作者信息

Lanitis Tereza, Khan Asif H, Proskorovsky Irina, Houisse Ivan, Kuznik Andreas, Kamat Siddhesh, Franco-Villalobos Conrado, Joulain Florence

机构信息

Tereza Lanitis Consulting Ltd, Methonis 1, Limassol, 3071, Cyprus.

Sanofi, 1 Av. Pierre Brossolette, 91380, Chilly-Mazarin, France.

出版信息

Contemp Clin Trials Commun. 2024 Nov 7;42:101390. doi: 10.1016/j.conctc.2024.101390. eCollection 2024 Dec.

Abstract

BACKGROUND

Models developed to date to simulate long-term outcomes of asthma have been criticized for lacking granularity and ignoring disease heterogeneity.

OBJECTIVE

To propose an alternative approach to modeling asthma and apply it to model long-term outcomes in a population with moderate-to-severe type 2 asthma (patients with raised fractional exhaled nitric oxide or eosinophils) and treated with conventional therapy.

METHODS

A discretely integrated condition event (DICE) approach was adopted, simulating individual profiles with asthma over patients' lifetime in terms of exacerbations, asthma-related death, and death unrelated to asthma. The timing of these events is dependent on profile characteristics including lung function, asthma control, exacerbation history, and other baseline characteristics or contextual factors. Predictive equations were derived from a clinical trial to model time to exacerbation, change in asthma control, lung function, and utility. Real-world studies were used to supplement data gaps. Outcomes evaluated included life expectancy, quality-adjusted life-years (QALY), number of exacerbations, and lung function over time.

RESULTS

Average annual rates of severe and moderate exacerbations were 1.82 and 3.08 respectively, with rates increasing over time. Lung function declined at a higher rate compared with the general population. Average life expectancy was 75.2 years, compared with 82.4 years in a matched general population. The majority of life-years were spent with uncontrolled asthma and impaired lung function.

CONCLUSION

Patients with moderate-to-severe type 2 asthma and a history of exacerbations suffer from frequent exacerbations and reduced lung function and life expectancy. Capturing multiple conditions to simulate long-term outcomes in patients with asthma may provide more realistic projections of exacerbation rates.

摘要

背景

迄今为止开发的用于模拟哮喘长期预后的模型因缺乏粒度和忽视疾病异质性而受到批评。

目的

提出一种模拟哮喘的替代方法,并将其应用于模拟中度至重度2型哮喘患者(呼出一氧化氮分数或嗜酸性粒细胞升高的患者)接受传统治疗后的长期预后。

方法

采用离散综合病情事件(DICE)方法,在患者的一生中模拟哮喘患者的个体情况,包括病情加重、哮喘相关死亡和与哮喘无关的死亡。这些事件的发生时间取决于个体特征,包括肺功能、哮喘控制情况、病情加重史以及其他基线特征或背景因素。从一项临床试验中得出预测方程,以模拟病情加重时间、哮喘控制变化、肺功能和效用。利用真实世界研究来填补数据空白。评估的结果包括预期寿命、质量调整生命年(QALY)、病情加重次数以及随时间变化的肺功能。

结果

重度和中度病情加重的年均发生率分别为1.82次和3.08次,且发生率随时间增加。与一般人群相比,肺功能下降速度更快。平均预期寿命为75.2岁,而匹配的一般人群为82.4岁。大部分生命年处于哮喘未得到控制和肺功能受损的状态。

结论

中度至重度2型哮喘且有病情加重史的患者经常病情加重,肺功能和预期寿命降低。考虑多种情况来模拟哮喘患者的长期预后可能会提供更现实的病情加重率预测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/723e/11616524/1ff76e7c5927/gr1.jpg

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