Identification of early changes in multiple biomarkers following CFTR modulator initiation in patients with cystic fibrosis.

BACKGROUND

There are currently no early parameters that allow prediction of long-term responses to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator treatment on an individual level.

OBJECTIVES

To identify early parameters measured within 7 to 14 days after initiation of treatment with a CFTR modulator to assess CFTR modulator efficacy.

STUDY

DESIGN

Prospective observational study of patients diagnosed with CF who begin elexacaftor/tezacaftor/ivacaftor (ETI) therapy at 3 CF clinics in Switzerland (Geneva, Lausanne, Lucerne).

METHODS

Standardized measurements were taken within 2 months prior to and 7 to 14 days after starting CFTR modulator treatment.

RESULTS

ETI treatment was started on 47 patients [median age: 12 years] of whom 12 (26%) were switching from lumacaftor/ivacaftor (n = 8) or tezacaftor/ivacaftor (n = 4) to ETI. A significant early treatment effect was observed for BMI z-score (p < 0.001) and inflammatory parameters (white blood cells (p = 0.006), neutrophils (p = 0.006), immunoglobulin G (p = 0.012), and fecal calprotectin (p = 0.002)). In CFTR functional assays, sweat chloride concentration and nasal potential difference testing [Δlow-chloride+isoproterenol, Sermet score, and Wilschanski index] improved significantly (all p < 0.001). Improvement was also observed in lung function (FVC, FEV1, MMEF25-75, LCI2.5%) (all p < 0.001). No changes were found for blood pressure, SpO2, respiratory rate, erythrocyte sedimentation rate, C-reactive protein, and fecal elastase.

CONCLUSION

This study identified clinical, biologic, and functional parameters showing treatment effect early after initiation of CFTR modulator therapy. These parameters may serve as potential predictors of long-term responses to CFTR modulator treatment.