Cystic fibrosis transmembrane conductance regulator (CFTR) modulators in triple combination lead to better clinical results than placebo or an active control, with similar adverse events, in patients with cystic fibrosis (CF). This is according to the results of a meta-analysis of randomized controlled trials published in Frontiers in Pharmacology.
CF is characterized by the dysfunction of the CFTR protein, whose role is to regulate the proper flow of chloride and sodium ions in and out of cell membranes. When the protein does not function properly due to mutations in the gene that encodes it, the secretions of exocrine glands, such as those in the lungs, become abnormally thick and block the airways, leading to inflammation, infection, and respiratory failure.
CFTR modulators are disease-modifying therapies that address the underlying cause of CF. They are grouped into 3 classifications: CFTR potentiators “hold open” a key gate within the CFTR protein that is long enough to facilitate the transport of chloride and sodium ions across the channel, CFTR correctors aim to correct the folding defects within the protein, and CFTR amplifiers increase the amount of functional protein on the cell surface.
Read more about disease-modifying therapies for CF
Triple combination therapy consists of a next-generation corrector, a corrector, and a potentiator. Data on its efficacy in treating CF have been limited.
Here, a team of researchers led by Peiwen Li, MD, from the Department of Thoracic Surgery, The First Hospital of China Medical University in Shenyangconducted a meta-analysis of the literature to assess the safety and efficacy of the triple combination therapy according to different mutations and comparators.
The team found that the total change in lung function was higher with triple combination therapy than with triple placebo or the active control. The concentration of sweat chloride, a hallmark of CF, was also lower with triple combination therapy than with triple placebo or the active control. Finally, the pooled estimate of the CF Questionnaire-Revised (CFQ-R) score was higher with triple combination therapy than with triple placebo or the active control. There were no obvious differences in terms of adverse events between triple combination therapy and triple placebo or the active control.
“More well-designed [randomized controlled trials] are needed to support the efficacy and safety, and extend the indications for younger patients diagnosed with CF, to achieve radical treatment for CF before the development of the disease,” the researchers said.
Wang Y, Ma B, Li W, Li P. Efficacy and safety of triple combination cystic fibrosis transmembrane conductance regulator modulators in patients with cystic fibrosis: a meta-analysis of randomized controlled trials. Front Pharmacol. 2022;13:863280. doi:10.3389/fphar.2022.863280