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
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
YR 2022
UL http://openres.ersjournals.com/content/early/2022/07/28/23120541.00204-2022.abstract
AB Background : Although short-term efficacy of lumacaftor/ivacaftor (LUM/IVA) and tezacaftor/ivacaftor (TEZ/IVA) 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 CF (pwCF) ≥12 years, up to three years after the introduction of dual CFTR modulators.Methods : Annual data (2010–2019) were retrieved from the Dutch Cystic Fibrosis Registry. Longitudinal trends of percent predicted forced expiratory volume in 1 s (ppFEV1) 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 ppFEV1 70.5% (sd:23.4%)). ppFEV1 decline improved from −1.36%/year to −0.48%/year after modulator initiation (change: 0.88%, CI:0.35–1.39%, p=0.001). This change was even 1.40%/year (CI −0.0001–2.82%, p=0.050) higher in participants with baseline ppFEV1<40%. In adults, annual BMI trend was not altered (change: 0.10 kg·m−2·year−1, CI:-0.01–0.21, p=0.079). Annual BMI Z-score in children reversed from −0.08/year before modulator treatment to 0.06/year afterwards (change: 0.14/year, CI:0.06–0.22, p<0.001). Intravenous antibiotic treatment duration showed a three-fold reduction in the first year after modulator initiation (IRR: 0.28, CI:0.19–0.40, p<0.001), but the annual trend did not change in the subsequent years (IRR: 1.19, CI:0.94–1.50, p=0.153).Conclusion : Long-term effectiveness of dual CFTR modulator therapies on ppFEV1 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 ppFEV1 levels.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Danya Muilwijk has nothing to disclose.Conflict of interest: Domenique D. Zomer-van Ommen has nothing to disclose.Conflict of interest: Vincent A.M. Gulmans has nothing to disclose.Conflict of interest: Marinus J.C. Eijkemans has nothing to disclose.Conflict of interest: Cornelis K. van der Ent reports grants from Vertex, Eloxx, Proteostasis, Galapagos NV, ProQR, Gilead, TEVA, GSK and Nutricia (money to institution), outside of the submitted work.