RT Journal Article
SR Electronic
T1 Long-term effectiveness of dual CFTR modulator treatment of cystic fibrosis
JF ERJ Open Research
JO erjor
FD European Respiratory Society
SP 00204-2022
DO 10.1183/23120541.00204-2022
VO 8
IS 4
A1 Danya Muilwijk
A1 Domenique D. Zomer-van Ommen
A1 Vincent A.M. Gulmans
A1 Marinus J.C. Eijkemans
A1 Cornelis K. van der Ent
A1 Dutch Cystic Fibrosis Registry (NCFR) Steering Group:
A1 J. Altenburg
A1 S.W.J. Terheggen-Lagro
A1 H.G.M. Heijerman
A1 K.M. de Winter-de Groot
A1 M. Bakker
A1 R.A.S. Hoek
A1 H.M. Janssens
A1 R. van der Meer
A1 M. Nuijsink
A1 H. van der Vaart
A1 G.H. Koppelman
A1 L.H. Conemans
A1 M.A.G.E. Bannier
A1 J.J. Noordhoek
YR 2022
UL http://openres.ersjournals.com/content/8/4/00204-2022.abstract
AB Background Although short-term efficacy of lumacaftor/ivacaftor and tezacaftor/ivacaftor is clearly established in clinical trials, data on long-term effectiveness is limited. This registry-based cohort study assessed real-world longitudinal outcomes of F508del-homozygous people with cystic fibrosis (pwCF) ≥12 years, up to 3 years after the introduction of dual cystic fibrosis transmembrane conductance regulator (CFTR) modulators.Methods Annual data (2010–2019) were retrieved from the Dutch Cystic Fibrosis Registry. Longitudinal trends of per cent predicted forced expiratory volume in 1 s (FEV1 % pred) decline, body mass index (BMI), BMI Z-score and intravenous antibiotic treatment duration before and after CFTR modulator initiation were assessed with linear and negative binomial mixed models.Results We included 401 participants (41.9% female, baseline age 24.5 years (IQR 18.0–31.5 years), baseline mean±sd FEV1 70.5±23.4% pred). FEV1 decline improved from −1.36% pred per year to −0.48% pred per year after modulator initiation (change: 0.88% pred, 95% CI: 0.35–1.39%, p=0.001). This change was even 1.40% pred per year (95% CI: −0.0001–2.82%, p=0.050) higher in participants with baseline FEV1 <40% pred. In adults, annual BMI trend was not altered (change: 0.10 kg·m−2·year−1, 95% CI:−0.01–0.21, p=0.079). Annual BMI Z-score in children reversed from −0.08 per year before modulator treatment to 0.06 per year afterwards (change: 0.14 per year, 95% CI: 0.06–0.22, p<0.001). Intravenous antibiotic treatment duration showed a three-fold reduction in the first year after modulator initiation (incidence rate ratios (IRR): 0.28, 95% CI: 0.19–0.40, p<0.001), but the annual trend did not change in the subsequent years (IRR: 1.19, 95% CI: 0.94–1.50, p=0.153).Conclusion Long-term effectiveness of dual CFTR modulator therapies on FEV1 decline, BMI and intravenous antibiotic treatment duration is less pronounced in a real-world setting than in clinical trials and varies considerably between pwCF and different baseline FEV1 levels.Long-term effectiveness of dual CFTR modulator therapies on FEV1 decline, BMI and intravenous antibiotic treatment duration is less pronounced in a real-world setting than reported in previous clinical trials https://bit.ly/3QippTi