(252) Real World Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Decreasing Cystic Fibrosis Pulmonary Exacerbations in Health-System Based Specialty Pharmacy Patients

Background: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is the newest cystic fibrosis transmembrane conductance regulator (CFTR) modulator approved for patients with cystic fibrosis. This therapy is a highly effective modulator therapy indicated for the treatment of cystic fibrosis in patients with a single copy of F508del.[1] In randomized controlled trials, ELX/TEZ/IVA showed improvement of lung function, decrease in respiratory symptoms, reduction in pulmonary exacerbations and weight gain.[2,3] However, long-term clinical benefit of ELX/TEZ/IVA in real-world settings is still under investigation.

Methods: This retrospective within-groups study examined cystic fibrosis patients receiving care from a single academic health-system specialty pharmacy. Subjects were included who initiated ELX/TEZ/IVA and continued therapy for greater than one year. Retrospective data from the index year prior to ELX/TEZ/IVA initiation and the year following was collected by medical records review. The primary end point was the difference in number of severe cystic fibrosis exacerbations defined as those requiring hospitalization or intravenous antibiotics in index year as compared to one year post ELX/TEZ/IVA initiation. The secondary endpoints included change in ppFEV1 from baseline and change in body mass index (BMI) from baseline.

Results: A total of 76 patients were included in the final analysis with a median age of 25 years. In the post ELX/TEZ/IVA year, subjects had a significant mean decrease in severe exacerbations (-0.72; p< 0.0001). Decreases in severe exacerbations remained significant in subgroups of patients with prior CFTR modulator exposure (-0.56; p =0.006; n=46) and those with moderate to severe lung disease (-0.98; p < 0.0001; n=41). After one year of ELX/TEZ/IVA therapy, subjects experienced a significant mean absolute increase in ppFEV1 of 6.07% (p=0.0125) and increase in BMI of 1.46 kg/m2 ( p=0.0002).

Conclusions: In this single center, retrospective study, one year of ELX/TEZ/IVA therapy was associated with improvement in clinical status of patients with cystic fibrosis. Consistent with clinical trials, patients in this study experienced less exacerbations, along with increased lung function and BMI.

Acknowledgements:

References: [1] Trikafta [package insert]. Boston, MA: Vertex Pharmaceuticals, Inc; 2021.
[2] Middleton PG, Mall mA, Drevinek P, Lands LC, McKone EF, Polineni D, Ramsey BW, Taylor-Cousar JL, Tullis E, Vermeulen F, Marigowda G, McKee CM, Moskowitz SM, Nair N, Savage J, Simard C, Tian S, Waltz D, Xuan F, Rowe SM, Jain R, V.X.S. Group, Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele, N Engl J Med. 2019; 381(19): 1809-1819.
[3] Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, Mall MA, Welter JJ, Ramsey BW, McKee CM, Marigowda G, Moskowitz SM, Waltz D, Sosnay PR, Simard C, Ahluwalia N, Xuan F, Zhang Y, Taylor-Cousar JL, McCoy KS, V.X.T. Group, Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomized, phase 3 trial. Lancet. 2019; 394(10212):1940-1948.