Real-world effectiveness of elexacaftor/tezacaftor/ivacaftor on the burden of illness in adolescents and adults with cystic fibrosis

Thomas Keens; Veena Hoffman; Ia Topuria; Ken Elder; Shannon Cerf; Kyra Mulder; Jon Roberts; Jerimiah Lysinger; Maria Del Carmen Reyes; Maria Berdella; Anne Marie Cairns; Manu Jain; Vaidyanathan Ganapathy; Yiyue Lou; Bassem Morcos; Chuntao Wu; Laura Sass; VX19-CFD-003 Study Group

doi:10.1016/j.heliyon.2024.e28508

Real-world effectiveness of elexacaftor/tezacaftor/ivacaftor on the burden of illness in adolescents and adults with cystic fibrosis

Heliyon. 2024 Mar 26;10(7):e28508. doi: 10.1016/j.heliyon.2024.e28508. eCollection 2024 Apr 15.

Authors

Thomas Keens¹, Veena Hoffman², Ia Topuria², Ken Elder², Shannon Cerf², Kyra Mulder², Jon Roberts³, Jerimiah Lysinger⁴, Maria Del Carmen Reyes¹, Maria Berdella⁵, Anne Marie Cairns⁶, Manu Jain⁷, Vaidyanathan Ganapathy⁸, Yiyue Lou⁸, Bassem Morcos⁸, Chuntao Wu⁸, Laura Sass⁹; VX19-CFD-003 Study Group

Affiliations

¹ Children's Hospital of Los Angeles, Los Angeles, CA, USA.
² OM1 Incorporated, Boston, MA, USA.
³ Driscoll Children's Hospital, Corpus Christi, TX, USA.
⁴ Billings Clinic Hospital, Billings, MT, USA.
⁵ Northwell Health, New York, NY, USA.
⁶ Maine Medical Center, Portland, ME, USA.
⁷ Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
⁸ Vertex Pharmaceuticals Incorporated, Boston, MA, USA.
⁹ Children's Hospital of The King's Daughter, Norfolk, VA, USA.

Abstract

Background: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to be safe and efficacious in people with cystic fibrosis (CF) aged ≥2 years. Here, we describe results from an observational study assessing change in burden of illness following initiating ELX/TEZ/IVA in real-world settings.

Methods: This US-based, multicenter, observational study used data from electronic medical records to evaluate real-world burden of illness before and after ELX/TEZ/IVA initiation in people with CF aged ≥12 years heterozygous for F508del and a minimal function mutation (F/MF) or an uncharacterized CFTR mutation. Endpoints included absolute change from baseline in percent predicted forced expiratory volume in 1 s (ppFEV₁), body mass index (BMI) and BMI-for-age z-score, glycated hemoglobin (HbA1c), and numbers of pulmonary exacerbations (PEx).

Results: Overall, 206 people with CF were enrolled (mean [SD] age 22.5 [11.1] years; 192 [93.2%] with F/MF genotype). Mean follow-up was 15.6 (SD, 1.6) months. Improvements in ppFEV₁ (7.3 [95% CI: 5.7, 8.8] percentage points) were observed from baseline through follow-up. Increases in BMI (1.40 [95% CI: 1.07, 1.77] kg/m²) and BMI-for-age z-score (0.14 [95% CI: 0.00, 0.28]) were also observed from baseline at 12 months. The estimated annualized rate of any PEx was 1.31 at baseline and 0.61 over follow-up (rate ratio 0.47 [95% CI: 0.39, 0.55]), with annualized rates of PEx requiring antibiotics and hospitalizations of 0.55 and 0.88 in the baseline period and 0.12 and 0.36 over follow-up (rate ratios 0.22 [95% CI: 0.15, 0.31] and 0.41 [95% CI: 0.32, 0.51]), respectively. Absolute change in HbA1c was -0.22 (95% CI: -0.38, -0.06) from baseline through follow-up.

Conclusions: ELX/TEZ/IVA treatment was associated with improved lung function, increased BMI, reduced frequency of PEx, and improved (i.e., reduced) HbA1c. These results confirm the broad clinical benefits of ELX/TEZ/IVA seen in clinical trials and show the potential for ELX/TEZ/IVA to improve markers of glucose metabolism.

Keywords: Burden of disease; Cystic fibrosis; Elexacaftor; Ivacaftor; Real-world; Tezacaftor.