TABLE 1.
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/open | Overall effect: lung function | Overall effect: exacerbation reduction | Patients with severe disease (FEV1 <40% pred) | Lung function increase (% points) in severe disease | Exacerbation reduction in severe disease | Effect on weight or BMI in severe disease | Effect on quality of life (mean CFQ-R) in severe disease |
| IVA | ||||||||
| Ramsey [6] | G551D/any; RCT | 10.6%# | 55%# | NA | NA | NA | NA | NA |
| De Boeck [13] | Non-G551D gating/any; RCT | 10.7%# | NA | 0 | NA | NA | NA | NA |
| Hebestreit [10] | G551D/any; open, EAP | NA | NA | 14 (100%) | 5.2±5.6¶; median 3.9 (−4.1–16.8)+ | NA | 2.1±2.4 kg¶; median 1.1 (−0.3–6.3) kg+ | NA |
| Barry [9] | G551D/any; open, EAP | NA | NA | 21 (100%) | 4.2§ | 49%§,f | 1.8 kg§; median 2.3 (−0.4–4.2) kg+ | NA |
| Taylor-Cousar [11] | G551D/any; open, EAP | NA | NA | 44 (100%) | 4.8±0.5¶; (−13.1–22.7)+ | NA | 3.3±4.0 kg¶; (−2.3–14.4) kg+ | NA |
| Salvatore [12] | Non-G551D gating/any; open, EAP | NA | NA | 13 (100%) | 11.5§ | 51%§,¶¶ | 3.0 kg§ | NA |
| LUM/IVA | ||||||||
| Wainright [14] and Elborn [15] | F508del/F508del; RCT, subgroup analysis | 2.6–4.0%# | 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; open | NA | NA | 53 (37 completed 3 months) | 3.19§ | NA | BMI 0.03 kg·m−2§ | NA |
| Taylor-Cousar [17] | F508del/F508del; open | NA | NA | 46 (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; open | NA | NA | 20 (10 completed) | +2.5## | 60%§,¶¶ | BMI 0.9 kg·m−2## | NA |
| Diab-Cáceres [19] | F508del/F508del; open | NA | NA | 20 | 61%§,¶¶ | |||
| TEZ/IVA | ||||||||
| Taylor-Cousar [21] | F508del/F508del; RCT | 4.0 (3.1–4.8)#,++ | 36%#,++ | 27 (9.4%) | 3.5 (1.0–6.1)#,++ | NA | NA | NA |
| Rowe [22] | F508del/RF; RCT (crossover) | 6.8 (5.7–7.8)#,++ | 46% | 22 (9%) | 4.4 (1.1–7.8)#,++ | NA | NA | NA |
| ELX/TEZ/IVA | ||||||||
| Middleton [23] | F508del/MF; RCT | 13.8 (12.1–15.4)#,++ | 63% | 18 (9%) | 15.2 (7.3–23.1)#,++ | NA | NA | NA |
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.