(571) Impact of HEMT on Chronic Rhinosinusitis: 2-year Follow-up with Machine Learning CT Analysis and Patient Reported Outcomes

Background:

Introduction: Elexacaftor/tezacaftor/ivacaftor (ETI) is a highly effective cystic fibrosis transmembrane conductance regulator therapy (HEMT) that effectuates substantial improvements in pulmonary and extrapulmonary disease including chronic rhinosinusitis (CRS) for people with CF (PwCF) who are hetero- or homozygous for F508del. We investigated the long-term impact of ETI on CF-related CRS using sinus computed tomography (CT) scan images analyzed via machine-learning based methods and patient-reported outcome (PRO) measures.

Methods: Methods: Adult PwCF with CRS with genotype F508del/F508del or F508del/minimal function who clinically initiated ETI enrolled in a prospective, observational study starting in August 2019. Outcome measures were obtained at three time points: baseline, after 6 months of ETI, and after 2 years of ETI. Additionally, PROs were collected monthly between baseline and 6 months and quarterly between 6 months and 2 years. The primary endpoint was change in sinus CT opacification scores assessed via a convolutional neural network (CNN) algorithm. Secondary endpoints included changes in validated PRO measures to evaluate sinonasal quality of life, health utility value, and productivity loss. Findings in changes in these measures after 6 months of treatment with ETI in 25 participants have been previously reported.[1]

Results:

Results: Thirty subjects initially enrolled and completed baseline data collection. Twenty-three individuals are scheduled to complete 2-year follow-up with analysis by 06/01/22. In the final abstract, we will report mean sinus CT opacification via CNN analysis, sinus CT Lund Mackay score, 22-question SinoNasal Outcome Test score, health utility value, absenteeism and presenteeism after 2 years of treatment with ETI. We will compare these values to data from baseline and after 6 months of ETI treatment using mixed effect models to account for repeated measures. We will analyze if factors including genotype, prior sinus surgery, and use of prior modulator therapy impact improvements with ETI.

Conclusions:

Conclusions: The results are anticipated to demonstrate that the clinically impactful objective and subjective improvement in CRS observed after 6 months of HEMT treatment are sustained over 24 months.

Acknowledgements: Grant funding from the Cystic Fibrosis Foundation and the Marshall and Margherite McComb Foundation was used to support this project (NCT04056702).

References: 1. Beswick, D, Humphries, S, Balkissoon C, et al. Impact of CFTR therapy on chronic rhinosinusitis and health status: Deep learning CT analysis and patient-reported outcomes. Ann Am Thorac Soc. 2022 Jan;19(1): 12-19. PMID: 34436985