#00053Is there a role for sweat chloride levels as a marker of clinical response to Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis patients?

Pereira Fernandes 1, Fragoso 2, Lopes 2, Azevedo 2.
1Hospital Prof. Doutor Fernando Fonseca, EPE - Lisboa (Portugal), 2Cystic Fibrosis Reference Centre, Hospital de Santa Maria – Centro Hospitalar Universitário de Lisboa Norte (CHULN), EPE - Lisboa (Portugal).

Abstract

Introduction: Sweat chloride test (SCT) is the diagnostic gold standard for Cystic Fibrosis (CF). In the new era of highly effective modulator therapy, this test has been used as a biomarker for assessing therapy response.
 
Objectives: To evaluate the SCT variability in response to Elexacaftor/Tezacaftor/Ivacaftor (ETI) and compare this variability to surrogate endpoints of clinical effectiveness in patients with CF (pwCF) followed at a Portuguese CF Reference Centre.
 
Methods: Retrospective analysis of clinical records of adult pwCF on ETI for at least one year. Epidemiological and clinical variables were collected both at baseline and at 12 months of treatment [sweat chloride levels (SC), BMI, FEV1 and pulmonary exacerbation rates – Pex]. Comparisons between pre and post-ETI values were performed. Pearson and Spearman’s r were performed to assess correlations.
 
Results: Out of the 53 adult patients with CF on ETI at our Centre, 36 met the inclusion criteria and were included in the analysis. SC mean drop of 43 mmol/L (p<0.001). BMI variation +1.1 kg/m2 (p<0.001). FEV1 +0.271 L and ppFEV1 +10% (p<0.001). PEx rate drop of -1.1 exacerbation/year after one year of treatment (p<0.001). SC drop correlation with FEV1, BMI variation and PEx rate were all nonsignificant (p>0.05).

Conclusions: In our population, the magnitude of SC variation was not correlated with the magnitude of lung function improvement or reduction in PEx in pwCF treated with ETI. Although these results must be interpreted with caution, they seem to reflect a common finding. Future studies are needed to consider the role of SCT as a surrogate marker of clinical effectiveness of ETI.