TOPLINE:

Treatment with elexacaftor-tezacaftor-ivacaftor (ETI) was associated with rapid and substantial reductions in levels of systemic inflammatory markers by 3 months, an effect maintained through 24 months in patients with cystic fibrosis. Moreover, these reductions correlated with improvements in lung function.

METHODOLOGY:

• Investigators conducted a prospective multicenter study to examine the longitudinal effects of initiating ETI therapy on systemic inflammation and its association with lung function in patients with cystic fibrosis.
• They included 198 patients, ie, 49 children aged 6-11 years (median age, 9 years) and 149 individuals aged 12 years or older (median age, 22 years), as well as and 74 age-matched healthy control individuals.
• Peripheral blood neutrophil counts and levels of C-reactive protein (CRP) and proinflammatory cytokines — granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-17A, IL-1-beta, IL-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) — were measured and compared with serum samples from control individuals.
• Assessments were performed at baseline and at 3, 12, and 24 months after therapy initiation.

TAKEAWAY:

• Within 3 months of therapy, median neutrophil counts and CRP levels fell to 71% and 40% of baseline values, respectively (P < .05 for both).
• Median levels of all other proinflammatory cytokines decreased by more than 40% from baseline after 3 months of treatment (P < .05 for all), with the exception of IL-17A, which did not change significantly despite a steady decline.
• Levels of all cytokines returned to levels seen in control individuals at or before 24 months; however, IL-6 levels rose above those in control individuals until 24 months.
• Changes in neutrophil counts and CRP, G-CSF, IL-17A, IL-1-beta, IL-6, and MCP-1 levels significantly correlated with changes in percent-predicted forced expiratory volume in 1 second after 3 months of treatment (P < .05 for all), reflecting improvements in lung function.

IN PRACTICE:

“Clinically, our results thus advocate monitoring of systemic inflammation during ETI therapy as a proxy for disproportionate loss of lung function,” the investigators reported.

SOURCE:

The study was led by Olga Halle, Hannover Medical School, Clinic for Pediatric Pneumology, Allergology and Neonatology, Carl-Neuberg-Straße, Hannover, Germany, and Simon Y. Graeber, Department of Pediatric Respiratory Medicine, Immunology, and Critical Care Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany. It was published online on September 18, 2025, in European Respiratory Journal.

LIMITATIONS:

Because this was a real-world observational study, researchers could not fully exclude the effect of pulmonary exacerbations on systemic inflammation and may have included participants who had recent exacerbations. The study design also did not account for potential confounders such as seasonal respiratory infections associated with COVID-related social distancing, and recruitment was uneven across age groups.

DISCLOSURES:

The study was supported by the German Federal Ministry of Education and Research, Cluster of Excellence EXC 2155 “RESIST,” and the German Research Foundation. Several authors reported receiving institutional grants, honoraria, travel support, and consulting fees from; serving on advisory or monitoring boards of; and having other ties with various pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.