Kalydeco (ivacaftor) is known to increase the activity of the cystic fibrosis transmembrane conductance regulator (CFTR) protein in cystic fibrosis (CF) patients. A new study says the drug also improves lung function and reduces inflammation, but does not eradicate Pseudomonas bacteria infection.
The study, “Restoring CFTR Function Reduces Airway Bacteria and Inflammation in People With Cystic Fibrosis and Chronic Lung Infections,” appeared in the American Journal of Respiratory and Critical Care Medicine.
Chloride and thiocyanate ions use CFTR, an anion channel, to cross the cell membranes of lung epithelial cells. However, in CF patients, gene mutations have disabled the CFTR channel. For this reason, CF patients have a poor exchange of fluids in the lungs, resulting in a thickened mucus that traps bacteria and causes repeat respiratory infections.
Kalydeco, the first drug approved for CF, improves CFTR activity in patients with a specific CFTR gene mutation (G551D-CFTR). However, two previous studies did not find that it helped against bacterial infection and inflammation in patients’ airways. The sampling collection, assays used, or even experimental design could, however, have missed these effects.
In this study, researchers followed 12 CF patients — nine women and three men with a median age of 29.5 — with the G551D-CFTR gene mutation. Patients began treatment during the same week at the same research center. The same researchers collected and processed samples before and after treatment, and followed patients up to almost 1,000 days after treatment.
After two days, researchers detected a decrease in sweat chloride concentration as a readout of improved CFTR function. They also found a rapid decrease in Pseudomonas aeruginosa bacteria in patients’ sputum. These levels stayed low during the first year of treatment. After that, however, Pseudomonas infection rebounded in treated patients; none 0.had completely eradicated the bacteria during this study.
Researchers observed a significant decrease of inflammatory markers in the collected samples in the first week of treatment. Those markers continued to decline over two years. They also observed a decrease in airway mucus plugging before and one year after Kalydeco treatment in computerized tomography (CT) scans of patients.
“Ivacaftor caused marked reductions in sputum P. aeruginosa density and airway inflammation and produced modest improvements in radiographic lung disease in subjects with G551D-CFTR mutations,” said the team, using the generic name for Kalydeco. “However, P. aeruginosa airway infection persisted. Thus, measures that control infection may be required to realize the full benefits of CFTR-targeting treatments.”