Assistant Professor University of Missouri Columbia, Missouri, United States
Background: Elexacaftor/Tezacaftor/Ivacaftor, a combination cystic fibrosis transmembrane conductance regulator modulating medicine used to treat cystic fibrosis, has now been widely available to patients in the United States for the past 2-3 years. Multiple studies have reflected the improvement in respiratory symptoms and measurements noted by clinicians in their care for these patients. Previous modulator therapies found similar improvements in respiratory measurements, yet patients were found to have return of baseline P. aeruginosa densities at 2 years [Kidd T. AJRCCM. 2017; 195:1550-1552]. We investigated whether similar findings would occur with Elexacaftor/Tezacaftor/Ivacaftor therapy after two years and if improvements in pulmonary function testing measurements would persist as well.
Methods: A single center, retrospective study was performed using patient data from the adult cystic fibrosis program at the University of Missouri. A total of 50 patients were included in the analysis with each patient having completed a pulmonary function test and respiratory culture prior to and after starting therapy with Elexacaftor/Tezacaftor/Ivacaftor and again approximately 2 years later.
Results: A significant improvement in percent predicted forced expiratory volume in 1 second (ppFEV1%), percent predicted forced vital capacity (ppFVC%), absolute change of forced expiratory volume in 1 second (FEV1 L) and forced vital capacity (FVC L) was noted soon after starting Elexacaftor/Tezacaftor/Ivacaftor, as well as, a continued improvement at 2 years in ppFEV1% and ppFVC% (mean difference 95% CI 0.24 to 5.75, p-value = 0.03 and mean difference 95% CI 2.6 to 7.76, p-value = 0.0002, respectively). There was a significant reduction in the percentage of positive respiratory cultures for P. aeruginosa soon after starting Elexacaftor/Tezacaftor/Ivacaftor that persisted at two years (mean difference 95% -3.05 to -32.95, p-value = 0.015) (Figure 1A). Unlike P. aeruginosa, the percentage of positive respiratory cultures for S. aureus was not significantly changed soon after starting therapy but was found to be significantly reduced at two years (mean difference 95% -12.5 to -43.5, p-value = 0.0002) (Figure 1B). Like S. aureus, a significant reduction in percent of positive respiratory cultures for Aspergillusspecies was found at two years that was not seen right after starting therapy (mean difference 95% -2.02 to -25.98, p-value = 0.018) (Figure 1C). No significant difference was noted in cultures positive for Candida species after starting Elexacaftor/Tezacaftor/Ivacaftor although a trend towards significance was found at two years despite most cultures being obtained via throat swab cultures (before vs 2 years, mean difference 95% 3.5 to -39.5, p-value = 0.12) (Figure 1D).
Conclusions: Unlike previously seen return to baseline bacterial colonization densities at two years in early modulator therapies, patients at our center continue to have a reduction in percentage of positive respiratory cultures for S. aureus, P. aeruginosa and Aspergillus species at 2 years after starting Elexacaftor/Tezacaftor/Ivacaftor. A continued improvement in pulmonary function testing measurements were also found at 2 years warranting further investigation.
