Abstract：
BACKGROUND: Highly effective modulators of the CFTR channel have been demonstrated to dramatically impact disease progression and outcome. However, real-world data indicates that the magnitude of the clinical benefit is not equal among all patients receiving the treatment. We aimed to assess the variability in treatment response (as defined by the 6-month change in sweat chloride concentration, forced expiratory volume in one second [ppFEV1], body mass index [BMI], and CF Questionnaire-Revised [CFQ-R] respiratory domain score) and identify potential predictors in a group of patients receiving Elexacaftor-Tezacaftor-Ivacaftor (ETI) triple combination therapy.
METHODS: This was a single-center, prospective cohort study enrolling adults with CF at a major center in Italy. We used linear regression models to identify a set of potential predictors (including CFTR genotype, sex, age, and baseline clinical characteristics) and estimate the variability in treatment response.
RESULTS: The study included 211 patients (median age: 29 years, range: 12-58). Median changes (10-90th percentile) from baseline were: - 56 mEq/L (-76; -27) for sweat chloride concentration, +14.5 points (2.5; 32.0) for ppFEV1, +0.33 standard deviation scores (-0.13; 1.05) for BMI and +17 points (0; 39) for the CFQ-R respiratory domain score. The selected predictors explained 23 % of the variability in sweat chloride concentration changes, 18 % of the variability in ppFEV1 changes, 39 % of the variability in BMI changes, and 65 % of the variability in CFQ-R changes.
CONCLUSIONS: This study highlights a high level of heterogeneity in treatment response to ETI, which can only be partially explained by the baseline characteristics of the disease.
METHODS: This was a single-center, prospective cohort study enrolling adults with CF at a major center in Italy. We used linear regression models to identify a set of potential predictors (including CFTR genotype, sex, age, and baseline clinical characteristics) and estimate the variability in treatment response.
RESULTS: The study included 211 patients (median age: 29 years, range: 12-58). Median changes (10-90th percentile) from baseline were: - 56 mEq/L (-76; -27) for sweat chloride concentration, +14.5 points (2.5; 32.0) for ppFEV1, +0.33 standard deviation scores (-0.13; 1.05) for BMI and +17 points (0; 39) for the CFQ-R respiratory domain score. The selected predictors explained 23 % of the variability in sweat chloride concentration changes, 18 % of the variability in ppFEV1 changes, 39 % of the variability in BMI changes, and 65 % of the variability in CFQ-R changes.
CONCLUSIONS: This study highlights a high level of heterogeneity in treatment response to ETI, which can only be partially explained by the baseline characteristics of the disease.
摘要：
背景:已经证明CFTR通道的高效调节剂显著影响疾病进展和结果。然而,现实世界的数据表明，在接受治疗的所有患者中，临床获益的幅度并不相等。我们旨在评估治疗反应的变异性（如6个月的汗液氯化物浓度变化所定义，一秒钟用力呼气量[ppFEV1]，体重指数[BMI]，和CF问卷修订的[CFQ-R]呼吸域评分），并确定一组接受Elexacaftor-Tezacaftor-Ivacaftor（ETI）三联疗法的患者的潜在预测因子。
方法：这是一个单中心，前瞻性队列研究在意大利的一个主要中心招募患有CF的成年人。我们使用线性回归模型来确定一组潜在的预测因子(包括CFTR基因型，性别,年龄,和基线临床特征）并估计治疗反应的变异性。
结果：该研究包括211名患者（中位年龄：29岁，范围：12-58）。与基线相比的中位数变化（10-90百分位数）为：-56mEq/L（-76;-27），ppFEV1+14.5分(2.5;32.0),BMI+0.33标准差评分(-0.13;1.05),CFQ-R呼吸域评分+17分(0;39)。选定的预测因子解释了23％的汗液氯化物浓度变化的变异性，PPFEV1变化的变异性为18%，39%的变异性在BMI的变化，CFQ-R变化的变异性为65%。
结论：这项研究强调了ETI治疗反应的高度异质性，这只能部分由疾病的基线特征来解释。
方法：这是一个单中心，前瞻性队列研究在意大利的一个主要中心招募患有CF的成年人。我们使用线性回归模型来确定一组潜在的预测因子(包括CFTR基因型，性别,年龄,和基线临床特征）并估计治疗反应的变异性。
结果：该研究包括211名患者（中位年龄：29岁，范围：12-58）。与基线相比的中位数变化（10-90百分位数）为：-56mEq/L（-76;-27），ppFEV1+14.5分(2.5;32.0),BMI+0.33标准差评分(-0.13;1.05),CFQ-R呼吸域评分+17分(0;39)。选定的预测因子解释了23％的汗液氯化物浓度变化的变异性，PPFEV1变化的变异性为18%，39%的变异性在BMI的变化，CFQ-R变化的变异性为65%。
结论：这项研究强调了ETI治疗反应的高度异质性，这只能部分由疾病的基线特征来解释。
