(172) Treatment Changes and Outcomes in Adults Taking Elexacaftor/Tezacaftor/Ivacaftor at Two Years: A Single-Center Experience

Background: The approval of the highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) in 2019 has led to substantial improvements in the overall health of people with cystic fibrosis (PwCF); some PwCF taking ELX/TEZ/IVA have changed their chronic daily therapies after starting treatment. In this retrospective observational study, we aimed to understand the clinical characteristics of individuals who made changes in chronic daily therapies, and the effects of these changes on clinical outcomes at two-year.



Methods: We conducted a single-center study at the Indiana University Adult Cystic Fibrosis Center between January 1, 2020, and March 12, 2020. Our study included patients who had been on ELX/TEZ/IVA for a minimum of 60-days and were performing daily airway clearance with either oscillating positive expiratory pressure or high-frequency chest wall oscillation and/or using one or more of the following respiratory medications: dornase alfa, hypertonic saline, or inhaled antibiotics. During the follow-up period, patients were queried about whether they had made any changes to their chronic daily therapy since initiating ELX/TEZ/IVA. Data recorded included age, sex at birth, mutation type, body mass index, baseline forced expiratory volume in the first second (FEV1), quality of life, prior modulator therapy, and history of difficulty sustaining daily care. Clinical outcomes were determined at 1- and 2-year after starting ELX/TEZ/IVA therapy based on FEV1, hospitalizations, and additional changes to chronic daily therapies, including the resumption of previously discontinued therapy. Data were analyzed using a paired two-tailed t-test.



Results: In the period of interest, 85 individuals (50.1% female) were seen. The mean age of participants was 30.0±9.6 years. At the first follow-up visit, 36% of patients either decreased or stopped chronic respiratory medication or airway clearance (Figure 1). Patients who changed therapy were comparatively older (32.5±10.8 years vs. 28.5±8.4 years, p=0.06), had a greater change in FEV1 (12.2±8.3% vs. 7.1±6.3%, p=0.002), and had a large but insignificant change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain (31.4±17.4 vs. 23.9±20.4, p=0.18) than those who did not. Furthermore, 38% of individuals who discontinued treatments at the first visit made further changes to therapy at 1-year follow-up, while 39% of individuals who did not modify therapy initially reported changes at 1-year follow-up. Only 17% of patients who had previously discontinued treatments had resumed one or more therapies at a 1-year follow-up visit. Among individuals who made changes to the chronic therapy and had a hospitalization in the year prior to initiating ELX/TEZ/IVA, 63% had no hospitalization at a 1-year follow-up visit. No significant changes in lung function were seen after stopping chronic daily therapies.

Conclusions: In a single-center, retrospective observational study, over one-third of PwCF decreased their chronic daily therapies after initiating ELX/TEZ/IVA. No adverse effects on lung function or hospitalizations were noted. Larger studies are needed to determine the safety of discontinuation of chronic daily respiratory therapies after starting ELX/TEZ/IVA.

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