Summary of effects of cystic fibrosis transmembrane regulator modulators (ivacaftor (IVA), lumacaftor (LUM), tezacaftor (TEZ) and elexacaftor (ELX)) in people with severe lung function impairment from published trials and case series, not including case reports of single patients

First author [ref.]Population; study design: RCT/openOverall effect: lung functionOverall effect: exacerbation reductionPatients with severe disease (FEV1 <40% pred)Lung function increase (% points) in severe diseaseExacerbation reduction in severe diseaseEffect on weight or BMI in severe diseaseEffect on quality of life (mean CFQ-R) in severe disease
 Ramsey [6]G551D/any; RCT10.6%#55%#NANANANANA
 De Boeck [13]Non-G551D gating/any; RCT10.7%#NA0NANANANA
 Hebestreit [10]G551D/any; open, EAPNANA14 (100%)5.2±5.6; median 3.9 (−4.1–16.8)+NA2.1±2.4 kg; median 1.1 (−0.3–6.3) kg+NA
 Barry [9]G551D/any; open, EAPNANA21 (100%)4.2§49%§,f1.8 kg§; median 2.3 (−0.4–4.2) kg+NA
 Taylor-Cousar [11]G551D/any; open, EAPNANA44 (100%)4.8±0.5; (−13.1–22.7)+NA3.3±4.0 kg; (−2.3–14.4) kg+NA
 Salvatore [12]Non-G551D gating/any; open, EAPNANA13 (100%)11.5§51%§,¶¶3.0 kg§NA
 Wainright [14] and Elborn [15]F508del/F508del; RCT, subgroup analysis2.6–4.0%#39–61%#81 (7.3%)3.3 (0.2–6.4)– 3.7 (0.5–6.9)#,++53–41%#,§BMI 0.3 (−0.2–0.8) and 0.6 (0.1–1.2) kg·m−2#,++3.3 (5.2–11.7) and −4.2 (−12–3.7)#,++
 Hubert [16]F508del/F508del; openNANA53 (37 completed 3 months)3.19§NABMI 0.03 kg·m−2§NA
 Taylor-Cousar [17]F508del/F508del; openNANA46 (35 completed 24 weeks)−0.4 (−1.9–1.1)#,++64%§,¶¶BMI 0.29 (0.17) kg·m−2§,++2.5 (−1.0–5.9)++
 Murer [18]F508del/F508del; openNANA20 (10 completed)+2.5##60%§,¶¶BMI 0.9 kg·m−2##NA
 Diab-Cáceres [19]F508del/F508del; openNANA2061%§,¶¶
 Taylor-Cousar [21]F508del/F508del; RCT4.0 (3.1–4.8)#,++36%#,++27 (9.4%)3.5 (1.0–6.1)#,++NANANA
 Rowe [22]F508del/RF; RCT (crossover)6.8 (5.7–7.8)#,++46%22 (9%)4.4 (1.1–7.8)#,++NANANA
 Middleton [23]F508del/MF; RCT13.8 (12.1–15.4)#,++63%18 (9%)15.2 (7.3–23.1)#,++NANANA

Brackets indicate 95% confidence intervals, unless otherwise stated. RCT: randomised controlled trial; FEV1: forced expiratory volume in 1 s; BMI: body mass index; CFQ-R: Cystic Fibrosis Questionnaire-Revised; NA: not assessed; EAP: expanded access programme; RF: residual function CFTR mutation; MF: minimal function CFTR mutation. #: increase over placebo; : mean±sd, change from baseline; +: range, change from baseline; §: mean change from baseline; ƒ: days with antibiotics for pulmonary exacerbation, annualised; ##: median, change from baseline; : exacerbations per year per patient; ++: least mean square.