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.
| Original language | English (US) |
|---|---|
| Article number | e28508 |
| Journal | Heliyon |
| Volume | 10 |
| Issue number | 7 |
| DOIs | |
| State | Published - Apr 15 2024 |
Funding
This work was supported by Vertex Pharmaceuticals Incorporated. The sponsor was involved in the study design, analysis, and interpretation of the data with collaboration from the authors. The sponsor helped develop the report with input, review, and approval from the authors.The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All Authors report writing assistance was provided by Vertex Pharmaceuticals Incorporated. Laura Sass reports a relationship with Girl Scout Council of the Colonial Coast that includes: board membership. Yiyue Lou reports a relationship with Vertex that includes: employment. Bassem Morcos reports a relationship with Vertex Pharmaceuticals Incorporated that includes: employment. Chuntao Wu reports a relationship with Vertex Pharmaceuticals Incorporated that includes: employment. Shannon Cerf reports a relationship with OM1 Inc that includes: employment. Kyra Mulder reports a relationship with OM1 Inc that includes: employment. Veena Hoffman reports a relationship with OM1 Inc that includes: employment. Jerimiah Lysinger reports a relationship with Rocky Mountain Chapter of the CFF that includes: board membership. Chuntao Wu reports a relationship with Alexion Pharmaceuticals Inc that includes: equity or stocks. Chuntao Wu reports a relationship with Sanofi that includes: equity or stocks. Manu Jain reports a relationship with Vertex Pharmaceuticals Incorporated that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.The authors would like to thank the participants and their families for contributing to this study and acknowledge the VX19-CFD-003 study investigators and site coordinators, including Perry Brown (St. Luke's), Rebekah Brown (Vanderbilt), Aaron Chidekel (Nemours Delaware), Okan Elidemir (Nemours Pensacola), Zachary Holliday (University of Missouri), Jimmy Johannes (Memorial Care), Floyd Livingston (Nemours Orlando), Chad Marion (Wake Forest Health), Kathryn Moffett-Bradford (West Virginia University), and Victor Ortega (Wake Forest Health), for making this study possible. Medical writing support and editing support was provided by Nathan Blow, PhD, of Vertex Pharmaceuticals Incorporated, who may own stock or stock options in the company. Quality control review was provided by Complete HealthVizion, IPG Health Medical Communications, funded by Vertex Pharmaceuticals Incorporated.
Keywords
- Burden of disease
- Cystic fibrosis
- Elexacaftor
- Ivacaftor
- Real-world
- Tezacaftor
ASJC Scopus subject areas
- General
