Triple Combination Therapy Leads to Sustained Lung Function Improvements in Patients With Cystic Fibrosis and Advanced Lung Disease

After one year of treatment with the CFTR modulators elexacaftor-tezacaftor-ivacaftor, patients with cystic fibrosis (CF) and advanced lung disease had improvement in measures of lung function and BMI, according to research presented at the American Thoracic Society’s 2021 International Conference. Brent Bermingham, MD, from the Medical University of South Carolina, was the lead author of this report.

Explaining the rationale of their study, Dr. Bermingham and coauthors noted that previous phase III trials of triple combination therapy excluded patients with advanced lung disease, making it difficult to extrapolate the results to this patient subgroup. Having previously observed short-term clinical improvement in lung function with triple combination therapy in patients with CF and advanced lung disease, the researchers sought to determine the safety and efficacy of this approach in the longer-term.

This retrospective cohort included 50 adults with with FEV1<40% and/or other high-risk CF features who began triple combination therapy between November 2019 and February 2020. Approximately 42% of patients had high-risk disease features.

Response to therapy was assessed with repeat measurement of forced expiratory volume in 1 second percent predicted (FEV1pp), forced vital capacity percent predicted (FVCpp), and body mass index (BMI) measured at initial follow-up and at one year following the initiation of therapy.

After one year, mean FEV1pp increased 7.4%±7.0 over baseline (P<0.05), and FVCpp improved by 7.5%±8.12 (P<0.05). Notably, BMI increased by a mean of 1.93 kg/m2±2.56 over the course of 1 year (P<0.05). One patient died during the observation period, but there were no drug-related adverse events requiring treatment discontinuation.

“Further registry studies are needed to elucidate how this improvement in lung function alters disease trajectory and lung transplantation timing,” the authors concluded.