Figures
- Figure 1
Timeline of treatment advances in CF.
- Figure 2
Mechanisms by which mutations in the CF gene can disrupt normal CFTR function.
- Figure 3
Reported and potential respiratory and multisystem effects of CFTR modulators. GORD: gastro-oesophageal reflux disease.
Tables
- Table 1
CFTR modulators licenced for use by the European Medicines Agency (EMA)
Modulator Year of EMA licensing Age group Genetics Ivacaftor 2012 ≥6 years Heterozygous G551D 2014 ≥6 years Heterozygous for additional gating mutations# 2015 ≥2 years
≥18 yearsAs above
Heterozygous R117H2018 ≥12 months Heterozygous for gating mutations# 2019 ≥6 months As above 2020 ≥4 months Heterozygous R117H
Heterozygous for gating mutations#Lumacaftor/ivacaftor 2015 ≥12 years Homozygous Phe508del 2017 ≥6 years As above 2018 ≥2 years As above Tezacaftor/ivacaftor 2018 ≥12 years Homozygous Phe508del or Phe508del+residual function mutation¶ 2020 ≥6 years As above Elexacaftor/tezacaftor/ivacaftor 2020 ≥12 years Homozygous Phe508del or Phe508del+minimal function mutation 2021 ≥12 years Heterozygous Phe508del #: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1225P, S549N, S549R. ¶: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A>G, S945L, S977F, R1070W, D1152H, 2789+5G>A, 3272-26A>G, 3849+10kbC>T.
- Table 2
Clinical outcomes from major clinical trials in CF
Participants Absolute change in ppFEV1 from baseline Change in exacerbation rate DNase (Fuchs et al. [52], 1994) ≥5 years
ppFVC >40%5.8% (24 weeks) 28% reduction Nebulised tobramycin (Ramsey et al. [53], 1999) ≥6 years
ppFEV1 25–75%5% (20 weeks)# 26% reduction Azithromycin (Saiman et al. [54], 2003) ≥6 years
ppFEV1 ≥30%4.4% Hazard ratio 0.65 Hypertonic saline (Elkins et al. [55], 2006) ≥6 years
ppFEV1 ≥40%3.2% (4 to 48 weeks) 56% reduction Nebulised aztreonam (McCoy et al. [56], 2008) ≥6 years
ppFEV1 25–75%6.3% (4 weeks) 45% reduction Nebulised levofloxacin (Elborn et al. [57], 2015) ≥12 years
ppFEV1 25–85%0.1% (4 weeks) 10.5% reduction Ivacaftor (Ramsey et al. [11], 2011) ≥12 years
ppFEV1 40–90%
At least one Gly551Asp10.1% (4 weeks) 55% reduction Elexacaftor/tezacaftor/ivacaftor (Middleton et al. [29], 2019) ≥12 years
ppFEV1 40–90%
Phe508del MF13.8% (4 weeks) 63% reduction ppFEV1: percentage predicted forced expiratory volume in 1 s; ppFVC: percentage predicted forced vital capacity. #: approximated using data from supplementary appendix on absolute change in ppFEV1 rather than change from baseline.
