背景:立即症状控制之间的关系,尚未以综合方式评估缓解药物的使用和治疗反应的恶化风险以及改变其的因素。在这里,我们应用模拟方案来评估个体基线特征对中重度哮喘患者治疗反应的影响,这些患者使用丙酸氟替卡松(FP)常规维持剂量单药或丙酸氟替卡松/沙美特罗(FP/SAL)或布地奈德/福莫特罗(BUD/FOR)联合治疗。
方法:减少缓解药物使用(抽吸/24小时),症状控制评分的变化(ACQ-5),在一组具有不同基线特征的患者中模拟了超过12个月的年度恶化率(例如,自诊断以来的时间,哮喘控制问卷(ACQ-5)症状评分,吸烟状况,体重指数(BMI)和性别)使用来自大型III/IV期临床研究的药物-疾病模型。
结果:模拟场景表明,作为一名吸烟者,具有较高的基线ACQ-5和BMI,长期哮喘病史与使用缓解药物有关(p<0.01)。在治疗过程中,这种增加与更高的恶化风险和更高的ACQ-5评分相关。不管潜在的维持治疗。3个月后将无应答者转换为ICS单一疗法至联合疗法可立即减少缓解药物的使用(即1.3vs.FP/SAL和BUD/FOR为1.0抽吸/24小时,分别)。此外,将基线时ACQ-5>1.5的患者转换为FP/SAL导致的恶化比接受常规给药BUD/FOR的患者减少34%(p<0.01).
结论:我们已经确定了中度至重度哮喘患者的基线特征,这些特征与使用更多的缓解药物有关。症状控制不佳,加重风险较高。此外,考虑到长期治疗效果,不同吸入性皮质类固醇(ICS)/长效β受体激动剂(LABA)组合的效果差异显著.在临床实践中应考虑这些因素,作为对中重度哮喘症状患者进行个性化管理的基础。
在这项研究中,我们观察了不同的因素如何影响那些经常服用药物的中度至重度哮喘患者对哮喘治疗的反应。具体来说,我们想量化哮喘持续时间,症状控制程度和肺功能的差异,以及吸烟习惯,体重,性影响一个人对定期维持治疗的反应。使用基于从大量中重度哮喘患者中获得的模型的计算机模拟,我们探讨了在12个月内,在接受吸入型糖皮质激素单独或联合长效β受体激动剂治疗的患者的实际生活管理情况.我们看了他们用了多少缓解吸入器,他们对哮喘控制的评价有多好,以及他们哮喘发作的频率。把这些结果放在一起考虑,我们评估了治疗对持续症状和/或降低未来哮喘发作风险的效果.我们的模拟显示吸烟者,哮喘症状评分较高的人,肥胖的人,并且有更长的哮喘病史倾向于更频繁地使用他们的缓解吸入器。这与哮喘发作的风险较高和症状控制较差有关。将那些对皮质类固醇的初始治疗反应不佳的患者转换为联合治疗,可以减少他们需要的缓解吸入器的数量。此外,丙酸氟替卡松/沙美特罗联合治疗的效果大于布地奈德/福莫特罗.总之,我们的研究发现,某些患者特征可以预测患者对哮喘治疗的反应。
BACKGROUND: The relationship between immediate symptom control, reliever medication use and exacerbation risk on treatment response and factors that modify it have not been assessed in an integrated manner. Here we apply simulation scenarios to evaluate the effect of individual baseline characteristics on treatment response in patients with moderate-severe asthma on regular maintenance dosing monotherapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR).
METHODS: Reduction in reliever medication use (puffs/24 h), change in symptom control scores (ACQ-5), and annualised exacerbation rate over 12 months were simulated in a cohort of patients with different baseline characteristics (e.g. time since diagnosis, asthma control questionnaire (ACQ-5) symptom score, smoking status, body mass index (BMI) and sex) using drug-disease models derived from large phase III/IV clinical studies.
RESULTS: Simulation scenarios show that being a smoker, having higher baseline ACQ-5 and BMI, and long asthma history is associated with increased reliever medication use (p < 0.01). This increase correlates with a higher exacerbation risk and higher ACQ-5 scores over the course of treatment, irrespective of the underlying maintenance therapy. Switching non-responders to ICS monotherapy to combination therapy after 3 months resulted in immediate reduction in reliever medication use (i.e. 1.3 vs. 1.0 puffs/24 h for FP/SAL and BUD/FOR, respectively). In addition, switching patients with ACQ-5 > 1.5 at baseline to FP/SAL resulted in 34% less exacerbations than those receiving regular dosing BUD/FOR (p < 0.01).
CONCLUSIONS: We have identified baseline characteristics of patients with moderate to severe asthma that are associated with greater reliever medication use, poor symptom control and higher exacerbation risk. Moreover, the effects of different inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) combinations vary significantly when considering long-term treatment performance. These factors should be considered in clinical practice as a basis for personalised management of patients with moderate-severe asthma symptoms.
In this
study we looked at how different factors affect the response to asthma treatment in people with moderate to severe asthma who are taking regular medication. Specifically, we wanted to quantify how much asthma duration, differences in the degree of symptom control and lung function, as well as smoking habit, body weight, and sex influence how well someone responds to regular maintenance therapy. Using computer simulations based on models obtained from data in a large patient population with moderate–severe asthma, we explored scenarios that reflect real-life management of patients undergoing treatment with inhaled corticosteroids alone or in combination with long-acting beta agonists over a 12-month period. We looked at how much reliever inhaler they use, how well they rate their asthma control, and how often they have asthma attacks. By considering these results together, we evaluated how well the treatments work on ongoing symptoms and/or reduce the risk of future asthma attacks. Our simulations showed that smokers, people with higher asthma symptom scores, who are obese, and have a longer history of asthma tend to use their reliever inhalers more often. This was linked to a higher risk of having asthma attacks and worse symptom control. Switching those patients who do not respond well to their initial treatment with corticosteroid to combination therapy reduced how much reliever inhaler they need. Also, the effects of fluticasone propionate/salmeterol combination therapy were greater than budesonide/formoterol. In conclusion, our
study found that certain patient characteristics can predict how well someone responds to asthma treatment.