Ivacaftor alone was more effective at reducing pulmonary inflammation in children with cystic fibrosis (CF) than combined ivacaftor/lumacaftor or no treatment, according to a new study published in Pediatric Pulmonology.

Ivacaftor alone was associated with lower IL-8 and IL-1β cytokine concentrations, both of which have been associated with early life structural lung disease development.

“Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy is transforming the care of CF and is now used in infants as young as 4 months of age,” the authors wrote. “The direct effect of CFTR modulator therapy on lung inflammation, and the potential role for synergistic anti-inflammatory therapy, remains unclear.”

The research team profiled pulmonary inflammation in 3 groups of preschool-aged children with CF who were part of the AREST-CF cohort at a single center: untreated, treated with lumacaftor/ivacaftor, and treated with only ivacaftor, in addition to a control group of healthy children.

Read more about CF therapies

The children treated with ivacaftor alone had reduced concentrations of inflammatory mediators compared with untreated children, especially in terms of 2 important cytokines: IL-8 and IL-1β. Combined treatment with ivacaftor and lumacaftor did not lead to reduced cytokine levels compared with untreated children.

Overall, the authors found the profile of inflammatory mediators among ivacaftor-treated children was more like that of the healthy controls, and those undergoing combined treatment were more similar to untreated children with CF.

The authors note that the patient cohort was small and that there were significant differences in treatment duration and ages between the groups, which means the results should be interpreted with caution. However, the data still offer useful insights into the anti-inflammatory effects of ivacaftor on preschool children with CF, and they suggest that combined treatment might not be necessary in all cases.


Shanthikumar S, Ranganathan S, Neeland MR. Ivacaftor, not ivacaftor/lumacaftor, associated with lower pulmonary inflammation in preschool cystic fibrosis. Pediatr Pulmonol. Published online July 5, 2022. doi:10.1002/ppul.26063