Advanced cystic fibrosis – improved lung function with long-term triple therapy

Longer treatment with triple CFTR-modulation resulted in not only FEV₁ but also FVC amelioration in cystic fibrosis patients with high-risk features. This was found in a new study that thus confirmed benefits seen in pivotal trials for advanced disease.

The combination elexacaftor/tezacaftor/ivacaftor has demonstrated benefit in lung function improvement in clinical trials and was approved by the EMA as orphan drug to treat patients with cystic fibrosis (CF) who have at least one F508del mutation in the CFTR gene [1]. The currently presented retrospective cohort trial shed light on longer-term efficacy. The study included medical records of 50 adult patients with CF and advanced lung disease. Efficacy and safety of triple combination therapy (TC) with the CFTR-modulators was investigated [2]. A reason for the particular interest in the question is the exclusion of subjects with advanced lung disease from phase 3 trials for CF, resulting in a lack of knowledge about treatment of this patient group in terms of TC. Previously, the group of researchers had already demonstrated short-term outcome improvements with TC for patients with CF and advanced lung disease.

The participants all had a forced expiratory volume in 1 second percent of predicted (FEV₁pp) <40% or other high-risk features before they started TC. Baseline characteristics comprised 52% women, 64% patients who were homozygous for F508de, and a mean age of 32. Pre-treatment mean values were FEV₁pp 33.0, forced vital capacity per cent predicted (FVCpp) 54.3, and BMI 23.2 kg/m². TC was started between September 2019 and February 2020. The results of spirometry –performed at 2–12 weeks, 3­–9 months, and >9 months after TC commencement­– served as markers for treatment response, as did the change in BMI. The longer-term TC therapy resulted in a significant 8.4% increase in FEV₁pp (P<0.001) and a significant amelioration of FVCpp by 9.4% (P<0.001). Furthermore, positive results of TC were noted as increased BMI (25.1 kg/m²) and a reduction of exacerbations from 3.22 in 12 months to 1.25 (p<0.0001). Importantly, after TC, only 22% remained to have a transplant referral; before TC this was 63%. The authors wish for further investigations with data from more centres that contain rates of lung function loss, lung transplantation, and mortality.

1. https://www.ema.europa.eu/en/medicines/human/EPAR/kaftrio, accessed 30 May 2021.
2. Bermingham B, et al. A one-year retrospective analysis of the effect of elexacaftor-tezacaftor-ivacaftor on lung function in cystic fibrosis patients with advanced lung disease. Session TP32: Epidemiology, biomarkers, and therapy in CF and non-CF bronchiectasis. ATS 2021 International Conference, 14-19 May.

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Posted on 5 July, 20216 July, 2021