Plasma levels of chemokines decrease during elexacaftor/tezacaftor/ivacaftor therapy in adults with cystic fibrosis

Area of Science:

• Immunology
• Pulmonology
• Pharmacology

Background:

• Cystic fibrosis (CF) involves immune dysregulation, inflammation, and infection.
• CFTR modulator therapies target underlying protein defects, improving clinical outcomes for patients.
• This study investigates the impact of elexacaftor/tezacaftor/ivacaftor (ETI) on CF-associated inflammation, specifically systemic chemokines.

Purpose of the Study:

• To analyze the effects of triple CFTR modulator therapy (ETI) on systemic chemokine levels in people with CF.
• To assess changes in proinflammatory chemokines following ETI initiation in CF patients.

Main Methods:

• Plasma samples from 51 people with CF were analyzed using a bead-based immunoassay.
• Chemokine levels were quantified before, and at three and six months after initiating ETI therapy.
• Key chemokines measured included IL-8, MIP-3α, GROα, ENA-78, and I-TAC.

Main Results:

• ETI therapy led to significant improvements in lung function (ppFEV1) and decreased sweat chloride levels.
• Significant reductions were observed in plasma levels of MIP-3α, GROα, ENA-78, and I-TAC after six months of ETI treatment.
• A trend towards decreased IL-8 levels was noted, though it did not reach statistical significance.

Conclusions:

• ETI therapy demonstrates anti-inflammatory properties by reducing specific chemokines.
• The observed chemokine changes are predominantly linked to neutrophilic inflammation.
• ETI therapy targets a distinct set of chemokines, contributing to its clinical benefits in CF.