Journal Article

Real‐life efficacy and safety of elexacaftor/tezacaftor/ivacaftor on severe cystic fibrosis lung disease patients

Reijers, Monique H., Vonk, Steffie E. M., Haarman, Eric G., Roukema, Jolt, Maitland‐van der Zee, Anke H., Majoor, Christof J., Lub, Rianne, Neerincx, Anne H., Terheggen‐Lagro, Suzanne W. J., Bos, Lieuwe D., Kos, Renate, Fenn, Dominic W., Brinkman, Paul, Altenburg, Josje

2022

Overview

Elexacaftor/tezacaftor/ivacaftor (ETI) is a cystic fibrosis (CF) transmembrane conductance regulator modulator, which has shown efficacy in CF patients (≥6 years) with ≥1 Phe508del mutation and a minimal function mutation. In October 2019, ETI became available on compassionate use basis for Dutch CF patients with severe lung disease. Our objective was to investigate safety and efficacy of ETI in this patient group in a real‐life setting. A multicenter longitudinal observational study was conducted to examine changes in FEV1, BMI, and adverse events at initiation and 1, 3, 6, and 12 months after starting ETI. The number of exacerbations was recorded in the 12 months before and the 12 months after ETI treatment. Patients eligible for compassionate use had a FEV1 <40% predicted. Wilcoxon signed‐rank test analyzed changes over time. Twenty subjects were included and followed up for up to 12 months after starting ETI. Treatment was well tolerated with mild side effects reported, namely, rash (15%) and stomach ache (20%) with 80% resolving within 1 month. Mean absolute increase of FEV1 was 11.8/13.7% (p ≤ .001) and BMI was 0.49/1.87 kg/m2 (p < .001–0.02) after 1/12 months, respectively. In comparison to the number of exacerbations pretrial, there was a marked reduction in exacerbations after initiation. Our findings show long‐term effects of treatment with ETI in patients with severe CF lung disease in a real‐life setting. Treatment with ETI is associated with increased lung function and BMI, less exacerbations, and only mild side effects. Elexacaftor/tezacaftor/ivacaftor (ETI) is effective in a real‐life setting with severe cystic fibrosis lung disease patients. The effect maintains for up to 12 months and the treatment was well tolerated and reduced the number of exacerbations. Sputum production is significantly lower after ETI initiation.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Antibiotics / Body mass index / Cystic fibrosis / Cystic Fibrosis - drug therapy / Cystic Fibrosis - genetics / Documentation / elexacaftor/tezacaftor/ivacaftor / Humans / Lung diseases / modulators / Mutation / Observational studies / Original / Outpatient care facilities / Patients / Pharmacology / Phosphatase / Pyrrolidines - pharmacology / Pyrrolidines - therapeutic use / Questionnaires / sputum / Transplants & implants