(687) Impacts of elexacaftor/tezacaftor/ivacaftor on days of antibiotic treatment in people living with cystic fibrosis

Thursday, November 3, 2022

12:45 PM – 1:25 PM ET

Presenting Author(s)

Andrew S. Purdy, PharmD (he/him/his)

PGY-2 Infectious Diseases Pharmacy Resident
Indiana University Health
Indianapolis, Indiana, United States

Co-Author(s)

Hilary Vogt, PharmD, BCPPS

Pulmonary Clinical Pharmacist
Indiana University Health
Indianapolis, Indiana, United States

Background: People living with Cystic Fibrosis (PwCF) have pulmonary exacerbations that require antibiotics for treatment, and as a result often receive courses of inpatient, home intravenous, and home oral antibiotics. Elexacaftor/tezacaftor/ivacaftor is a highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator for PwCF. The purpose of this study is to evaluate the effect of elexacaftor/tezacaftor/ivacaftor on overall antibiotic use in PwCF, and in the subgroup of those with advanced lung disease (FEV1< 40%).

Methods: This was a retrospective cohort study of PwCF at the Indiana University Health adult cystic fibrosis (CF) clinic. Inclusion criteria for this study were PwCF seen at the Indiana University Health adult CF clinic. PwCF were excluded for not taking elexacaftor/tezacaftor/ivacaftor, having received it for less than 12 months, not having a year’s worth of records before and after beginning it, having received a lung transplant, participating in an elexacaftor/tezacaftor/ivacaftor clinical trial, or being treated for a nontuberculous mycobacterium (NTM) infection during the study period. The primary endpoint was the number of days of antibiotic therapy – inpatient, home intravenous, and home oral antibiotics - one year before starting elexacaftor/tezacaftor/ivacaftor versus one year after starting it. The key secondary endpoint was the primary endpoint in patients with advanced lung disease (FEV1< 40%). Other secondary endpoints included Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory, digestive, and physical domain scores, number of all-cause hospitalizations, days hospitalized for causes other than pulmonary exacerbations, days of inpatient antibiotics (days of hospitalization for pulmonary exacerbations), days of home intravenous antibiotics, days of home oral antibiotics, FEV1, and weight before and after starting elexacaftor/tezacaftor/ivacaftor. Endpoints were analyzed using a sign test or paired t-test depending on data distribution.

Results: 172 PwCF were included. 99 were excluded. 44% were female and 49% were F508del homozygous. 43% were naïve to previous CFTR modulator use, while 44% were previously on tezacaftor/ivacaftor, 5% were previously on lumacaftor/ivacaftor, and 9% were previously on ivacaftor. 17% of those included met the criteria for advanced lung disease. The median change in antibiotic therapy was -20 days (P< 0.001). In the advanced lung disease subgroup, the median change in antibiotic therapy was -22 days (P< 0.001). The median change in inpatient antibiotic treatment (pulmonary exacerbation hospitalization) was 0 days (P< 0.001). The median change in home intravenous antibiotic treatment was 0 days (P< 0.001). The median change in home oral antibiotic treatment was –14 days (P< 0.001). The median change in non-pulmonary exacerbation hospitalization was 0 days (P=0.055). The median change in number of all-cause hospitalizations was 0 (P< 0.001). Weight increased 3 kg (P< 0.001) and FEV1 increased 8% (P< 0.001) from baseline. CFQ-R scores increased 27.8 points (P< 0.001) in the respiratory domain, 11.1 points (P< 0.001) in the digestive domain, and 16.7 points (P< 0.001) in the physical domain.

Conclusions: Elexacaftor/tezacaftor/ivacaftor is effective in significantly reducing days of antibiotic therapy in PwCF, including those with advanced lung disease. It is a widely efficacious and beneficial drug for PwCF.

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