Figures
- FIGURE 1
Waterfall plots. a) Plot for the slope of FEV1 % pred in the year following starting LUM/IVA. Data show the individual patient (n=24) changes in absolute FEV1 % pred in the year following LUM/IVA commencement, determined by linear regression of all pulmonary function from commencement to 1 year post. Mean change (slope±se): 1.45% per year. b) Plot for changes in number of days of IVAB in the year following commencement of LUM/IVA compared with the year prior. Data show individual patient (n=24) changes in IVAB days (post-days−pre-days). Median (IQR) reduction: 13 (4–30) days. c) Plot for changes in number of days in hospital in the year following commencement of LUM/IVA compared with the year prior. Data show individual patient (n=24) changes in hospital days (post-days−pre-days). Median (IQR) reduction: 12 (3–30) days. FEV1: forced expiratory volume in 1 s; IVAB: intravenous antibiotic; LUM/IVA: lumacaftor/ivacaftor; IQR: interquartile range.
- FIGURE 2
Body composition changes in 24 adults receiving lumacaftor/ivacaftor for 1 year: a) weight, b) fat-free mass and c) fat mass. Data show each individual measurement. Bars show mean change from baseline at each time-point. p-values indicate differences in mean values between time-points using linear mixed effects modelling with Bonferroni correction for multiple comparisons.
- FIGURE 3
Venn diagram showing lack of clustering of clinical response domains for changes on lumacaftor/ivacaftor (LUM/IVA) in 24 adults# with cystic fibrosis. IVAB: intravenous antibiotic; FEV1: forced expiratory volume in 1 s. Data have taken the median response for each domain (annual change in IVAB usage (days), rate of change in FEV1 % pred and rate of change in weight (kg)). Numbers in the circles show patients with a response greater than the median change (where “response” is the change in rate between the year prior to starting LUM/IVA and the year following commencement). #: five patients had a response below the median change for all three domains.
Tables
- TABLE 1
Demographics and cystic fibrosis (CF) therapies in 24 adults with CF at baseline (prior to commencement of lumacaftor/ivacaftor)
Male 54.2 Age years 32.6±8.6 Height cm 169.0±10.4 BMI kg·m−2 20.3±2.7 FEV1 L 1.30±0.41 FEV1 % pred 34.7±7.4 FVC L 2.65±0.81 FVC % pred 57.8±10.0 FEF25–75% L 0.51±0.19 FEF25–75% % pred 13.3±4.2 Diagnosis of CF-related diabetes mellitus 33.3 Diagnosis of CF-related liver disease 33.3 Use of supplementary oxygen therapy 0.0 Azithromycin 87.5 Recombinant human DNase 58.3 Hypertonic saline 58.3 Inhaled antibiotics 41.4 Oral antibiotics 33.3 Inhaled corticosteroids 87.5 Oral corticosteroids 4.2 Long-acting β2-agonists 91.7 Long-acting muscarinic antagonists 4.2 Data are presented as % or mean±sd. BMI: body mass index; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; FEF25–75%: forced expiratory flow at 25–75% of FVC.
- TABLE 2
Health service utilisation data and rates of change of pulmonary function and weight in the year prior to and the year following commencement of lumacaftor/ivacaftor in 24 adults with cystic fibrosis
Year prior to commencement Year following commencement p-value Health service utilisation data Pulmonary exacerbations requiring hospitalisation n 3 (2–4) 1.5 (1–2) 0.0002 Hospitalisation (on ward) days 27 (18–58) (range 10–103) 17 (10–25) (range 1–70) 0.0002 IVAB usage days 45 (21–75) (range 10–280) 27 (11–52) (range 1–167) 0.0007 Annual rate of change in pulmonary function and weight FEV1 L −0.084±0.046 0.027±0.041 0.077 FVC L −0.04±0.10 0.00±0.06 0.75 FEF25–75% L −0.07±0.02 0.02±0.02 0.007 FEV1 % pred −2.10±1.18 1.45±1.13 0.035 FVC % pred −0.69±2.11 1.27±1.51 0.46 FEF25–75% % pred 0.07±0.20 0.07±0.05 0.97 Weight kg −0.62±0.89 2.60±0.88 0.013 Health service utilisation data are presented as median (interquartile range); pulmonary function and weight data show mean change per year (slope±se) using linear regression modelling of all clinical measurements in each year-long period. IVAB: intravenous antibiotic; FEV1: forced expiratory volume in 1 s; FVC: forced vital capacity; FEF25–75%: forced expiratory flow at 25–75% of FVC. p-value for difference between year prior and year following commencement (Wilcoxon signed-rank test for health service utilisation data; weighted linear regression analyses for pulmonary function and weight data).
- TABLE 3
Body composition during treatment with lumacaftor/ivacaftor in 24 adults# with cystic fibrosis
Baseline 1 month 6 months 1 year p-value Weight kg 58.4±12.1 59.0±11.3 60.6±10.9** 60.8±11.1 0.0007 Fat-free mass kg 46.1±11.2 45.8±10.9 46.7±11.0 46.2±10.7 0.49 Fat mass kg 12.5±6.7 13.5±6.4 14.0±5.8** 14.7±6.3*** <0.0001 BMI kg·m−2 20.3±2.7 20.5±2.4 21.1±2.1* 21.2±2.3** 0.0003 FFMI kg·m−2 15.9±2.5 15.8±2.4 16.1±2.4 16.0±2.3 0.48 FMI kg·m−2 4.4±2.4 4.8±2.4 4.9±2.2** 5.2±2.4*** <0.0001 TBW L 33.7±8.1 33.6±7.7 34.2±7.9 33.9±7.8 0.46 ICW L 19.2±5.5 19.2±5.5 19.7±5.3 19.5±5.2 0.27 ECW L 14.5±2.8 14.4±2.7 14.5±2.8 14.4±2.8 0.84 ECW % TBW 43.6±3.9 43.3±3.4 42.8±3.8 43.0±3.5 0.29 Phase angle ° 4.8±0.9 4.8±0.9 4.7±1.4 4.8±0.9 0.08 Data are presented as mean±sd, unless otherwise stated. BMI: body mass index; FFMI: fat-free mass index; FMI: fat mass index; TBW: total body water; ICW: intracellular water; ECW: extracellular water. #: n=24 for weight and BMI for all time-points, and for all data at 1 year; n=23 for all other measurements at baseline, 1 month and 6 month time-points (for one patient, useable bioelectrical impedance analysis could not be obtained at baseline and 1 month, and one patient missed the 6-month measurement). Individual p-values for change between baseline and that time-point (derived from the regression model with Bonferroni correction): *: p<0.05; **: p<0.005; ***: p<0.0001. Overall p-value is for the linear mixed effects regression model for effect of time on variables.
