Real-world outcomes: Lung clearance index improvements in Danish children with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor.

Wednesday, August 28, 2024

2:15 PM – 2:30 PM CEST

Location: Room XV

Presenting Author(s)

EH

Esben Herborg Henriksen, MD

PhD Student
Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark
KU/Copenhagen/Denmark, Denmark

Co-Author(s)

RS

Rikke Mulvad Sandvik, MD. PhD

Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Denmark
DF

Daniel Faurholt-Jepsen, MD, PhD

Department of Infectious Diseases, University Hospital of Copenhagen – Rigshospitalet, Cystic Fibrosis Centre, DK
Copenhagen, Denmark
MO

Mette F. Olsen

Senior Reseacher
Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark, Denmark
TP

Tacjana Pressler

3Department of Infectious Diseases, University Hospital of Copenhagen – Rigshospitalet, Cystic Fibrosis Centre, DK, Denmark
TB

Thomas Bryrup, MD

PhD Student
2Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark, Denmark
FB

Frederik F. Buchvald, MD, PhD

Senior Physician
Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark, Denmark
IM

Inger HM Mathiesen, MD, PhD

Consultant Physician
Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark, Denmark
TQ

Tavs Qvist, MD, PhD

Consultant Physician
Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark, Denmark
HO

Hanne V. Olesen, MD, PhD

Senior Physician
Danish Center of Pediatric Pulmonology and Allergology, Department of Pediatrics and Adolescents Medicine, University Hospital of Aarhus, Department of Clinical Medicine, Aarhus University, Denmark, Denmark
HR

Hanne LM Rubak, MD, PhD

Senior Physician
Danish Center of Pediatric Pulmonology and Allergology, Department of Pediatrics and Adolescents Medicine, University Hospital of Aarhus, Department of Clinical Medicine, Aarhus University, Denmark, Denmark
HS

Hanne LM Skov, MD, PhD

Senior Physician
Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark, Denmark
Camilla Bjørn Jensen, PhD

Senior pharmacoepidemiologist
Copenhagen Phase IV Unit – Phase4CPH Section for Data, Biostatistics and Pharmacoepidemiology, Center for Clinical Research and Prevention
Frederiksberg, Denmark
KG

Kim Gjerum Nielsen, Prof, Senior Physician

Professor in Pediatrics
Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark, Denmark

Background: The highly effective treatment with elexacaftor/tezacaftor/ivacaftor (ETI) is a breakthrough combination therapy for cystic fibrosis (CF). Nevertheless, there is a lack of real-world evidence regarding the effectiveness of this treatment concerning peripheral airway diseases in pediatric patients. Nitrogen multiple breath washout (N2MBW) testing provides indices of such peripheral airway pathology.

Objectives: With this real-world study we assessed the effectiveness of ETI treatment on lung clearance index (LCI2.5) in Danish children with CF.

Methods: This was a real-world, nationwide, pediatric study conducted at the two CF centers in Denmark. We included all children from the Danish CF Cohort with genetically confirmed CF, who had initiated ETI treatment, and had at least one N2MBW analysis in the data collection period (18 months pre and post ETI initiation). Linear mixed effect regression modeling adjusted for sex, F508del genotype, prior modulator treatment and software version was used to assess the effect of ETI as the change in LCI2.5 after 12-months of treatment. Participant ID and treatment center was included as random effect variables to account for within-subject correlation between test from the same individuals. We categorized measurements according to a published normative LCI2.5 z-scores (using N2MBW) dataset from healthy school-aged children. We then computed the changes in severity scale distribution before and after ETI treatment.

Results: The analyses included 131 children, 78% were homozygous for the F508del mutation, with mean (SD) age and baseline ppFEV1 of 11.5 (3.4) years and 92.5 (17.3), respectively, and a total of 339 N2MBW tests. The median (IQR) number of N2MBW tests per child was 3 (2-3), ranging from 1 to 10 measurements. after 12 months of treatment LCI2.5 improved by 1.7 units (95%CI: -2.1; -1.2, p< 0.001). Eighty-eight children were included in the severity scale analysis. The percentage of children with normal LCI2.5 (LCI z-score < 2) almost doubled (from 28% to 55%) and the percentage of children with very advanced lung disease (LCI2.5 z-score >8) was reduced three-fold (from 32% to 10%) after initiating ETI treatment.

Conclusions: This study finds that ETI therapy effectively improves lung health in children with CF, as evidenced by N2MBW test assessments. Although ppFEV1 levels appeared normal before starting ETI therapy, the use LCI revealed underlying structural lung damage. For many patients, this damage improved following ETI treatment.