Abstract
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.
Footnotes
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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.
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- Received April 28, 2022.
- Accepted July 26, 2022.
- Copyright ©The authors 2022
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