Improved Clinical Outcomes With Elexacaftor/Tezacaftor/Ivacaftor in Patients With Cystic Fibrosis and Advanced Lung Disease: Real-World Evidence From an Italian Single-Center Study

Abstract

The combination of Elexacaftor/Tezacaftor/Ivacaftor (ETI) has resulted in a significant improvement in lung function and global clinical parameters, which have not been previously achieved with other CFTR modulators. However, there is a paucity of evidence in the literature on the long-term use of ETI in adolescents and patients with severe pulmonary impairment. Furthermore, the response to ETI may differ between homozygotes and heterozygotes, as well as between naïve patients and those previously treated with other CFTR modulators. A retrospective study was conducted to examine changes in percent predicted forced expiratory volume in 1 s (ppFEV₁), body-mass index (BMI), and sweat chloride concentration (SwCl) at baseline and at 6, 12 and 24 months after the initiation of ETI. Secondary outcomes included the number of pulmonary exacerbations, Cystic Fibrosis Questionnaire-Revised (CFQ-R) score, adverse events, mortality and transplantation rates. 139 subjects were included and followed up for up to 2 years after starting ETI. The results demonstrated a significant improvement in ppFEV₁ and BMI after 12 months of therapy (respectively, 16%, p < 0.001; +1.5 kg/m², p = 0.005), with a slight decline in the values after 24 months. This effect was independent of genotype and showed a different degree of response in naïve subjects compared to patients previously treated with other CFTR modulators. SwCl decreased from 84 to 37 mmol/L over 24 months (p < 0.001). 58.3% reduction of PEx rate was observed compared to the number of exacerbations prior to ETI. Overall, lung function, SwCl, PEx rate, CFQ-R scores and BMI improved after 24 months of ETI treatment. ETI was well tolerated, and none of the patients interrupted the treatment due to toxicity.

Keywords: CFTR; Elexacaftor‐Tezacaftor‐Ivacaftor; cystic fibrosis; effectiveness; safety.

FIGURE 1

The figure illustrates the absolute change from baseline for each clinical characteristic: Percent predicted forced expiratory volume in 1 s (ppFEV₁), percent predicted forced vital capacity (ppFVC), body‐mass index (BMI), sweat chloride concentration (SwCl), CFQ‐R respiratory domain score measured at T0 (baseline), T6 (after 6 months of ETI), T12 (after 12 months of ETI), and T24 (after 24 months of ETI).

FIGURE 2

The figure illustrates the absolute change from baseline in percent predicted forced expiratory volume in 1 s (ppFEV₁), body‐mass index (BMI), sweat chloride concentration (SwCl), according to ppFEV₁ severity, measured at T0 (baseline), T6 (after 6 months of ETI), T12 (after 12 months of ETI), and T24 (after 24 months of ETI).

FIGURE 3

The figure illustrates the absolute change from baseline in percent predicted forced expiratory volume in 1 s (ppFEV₁), body‐mass index (BMI), sweat chloride concentration (SwCl), according to genotype, measured at T0 (baseline), T6 (after 6 months of ETI), T12 (after 12 months of ETI), and T24 (after 24 months of ETI).

FIGURE 4

The figure illustrates the absolute change from baseline in percent predicted forced expiratory volume in 1 s (ppFEV₁), body‐mass index (BMI), sweat chloride concentration (SwCl), according to CFTR modulator history, measured at T0 (baseline), T6 (after 6 months of ETI), T12 (after 12 months of ETI), and T24 (after 24 months of ETI).

FIGURE 5

The figure illustrates the absolute change from baseline in percent predicted forced expiratory volume in 1 s (ppFEV₁), according to CFTR modulator history and ppFEV₁ severity, measured at T0 (baseline), T6 (after 6 months of ETI), T12 (after 12 months of ETI), and T24 (after 24 months of ETI).