Jones Paul W, Gelhorn Heather, Karlsson Niklas, Menjoge Shailendra, Müllerova Hana, Rennard Stephen I, Tal-Singer Ruth, Wilson Hilary, Merrill Debora, Tabberer Maggie
Institute of Infection and Immunity, St George's University of London, United Kingdom.
Research and Development, GlaxoSmithKline, Uxbridge, United Kingdom.
Chronic Obstr Pulm Dis. 2017 Mar 21;4(2):132-140. doi: 10.15326/jcopdf.4.2.2017.0129.
In trials oflong-acting bronchodilators, health status is an important trial outcome, however the influence of baseline severity on response measured by St George's Respiratory Questionnaire (SGRQ) is not known. We have compared SGRQ changes between patients with chronic obstructive pulmonary disease (COPD) of mild-moderate severity or dyspnea (Global initiative for chronic Obstructive Lung disease [GOLD] grades 1 and 2; modified Medical Research Council [mMRC] grades 1 and 2) to those with severe-very severe severity or dyspnea (GOLD grades 3 and 4; mMRC grades 3 and 4). Combined individual patient data from the COPD Biomarkers Qualification Consortium database (trials of long-acting bronchodilators) were used comprising of patients from short-term (≤1-year duration; n=10802) and medium-term (2-4 years' duration; n=8963) studies. A repeated measures analysis of variance (ANOVA) was used to determine the effects of baseline severity (GOLD/mMRC) on SGRQ response to treatment. All treatment arms were combined. In short-term studies, milder patients showed a greater response than those with more severe disease in terms of GOLD grade (partial Eta = 0.03, < 0.0001) and mMRC grade (partial Eta = 0.05, < 0.0001). Similar results were seen in the medium-term studies (partial Eta = 0.02, < 0.0001; mMRC: partial Eta = 0.05, < 0.0001,). Patients with less severe airflow limitation and less severe dyspnea showed larger improvements in SGRQ score than more severely obstructed or dyspneic patients. Although these severity influences are small (2%-5% of the variance in SGRQ score), they do suggest that pre-specified separate analyses are warranted to test for differences in response, based on baseline severity.
在长效支气管扩张剂试验中，健康状况是一项重要的试验结果，然而，基线严重程度对圣乔治呼吸问卷（SGRQ）所测量的反应的影响尚不清楚。我们比较了轻度至中度严重程度或呼吸困难（慢性阻塞性肺疾病全球倡议组织[GOLD]1级和2级；改良医学研究委员会[mMRC]1级和2级）的慢性阻塞性肺疾病（COPD）患者与重度至极重度严重程度或呼吸困难（GOLD 3级和4级；mMRC 3级和4级）患者之间的SGRQ变化。使用了慢性阻塞性肺疾病生物标志物资格认定联盟数据库（长效支气管扩张剂试验）中的合并个体患者数据，这些数据来自短期（≤1年；n = 10802）和中期（2至4年；n = 8963）研究。采用重复测量方差分析（ANOVA）来确定基线严重程度（GOLD/mMRC）对SGRQ治疗反应的影响。所有治疗组均合并在一起。在短期研究中，就GOLD分级（偏η² = 0.03，P < 0.0001）和mMRC分级（偏η² = 0.05，P < 0.0001）而言，病情较轻的患者比病情较重的患者表现出更大的反应。在中期研究中也观察到了类似的结果（偏η² = 0.02，P < 0.0001；mMRC：偏η² = 0.05，P < 0.0001）。气流受限较轻和呼吸困难较轻的患者在SGRQ评分上的改善比阻塞或呼吸困难更严重的患者更大。尽管这些严重程度的影响较小（占SGRQ评分方差的2% - 5%），但它们确实表明有必要进行预先指定的单独分析，以检验基于基线严重程度的反应差异。
