(36) Respiratory Outcomes In The Era of High Quality Modulator Therapies: Results from the Tennessee and Mississippi Cystic Fibrosis Consortium

Background: Cystic Fibrosis (CF) is an autosomal recessive disease due to mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene that codes for the eponymous protein. Treatment modalities included therapies targeted at end organ damage until modulator therapy revolutionized CF care. Triple combination therapy with Elexacaftor / Tezacaftor/ Ivacaftor (ETI) studied on CF patients with one or two copies of the Phe 508 del mutation^{1, 2} showed significantly improved lung function, and decreased sweat chloride concentrations. On October 21, 2019, the FDA approved this medication for CF patients 12 years and older with at least one Phe 508 del mutation³. It is now approved for ages 6 and older. Post ETI, clinicians note fewer sick visits and improved lung function. Patients report less cough and sputum production. To confirm these observations, we looked at respiratory data across adult and pediatric Centers in two States before and after ETI therapy.

Methods: We analyzed CF Foundation Registry data on pediatric and adult CF patients at the 5 Centers in Tennessee and Mississippi for the year preceding, and one year after initiation of ETI. The best value for FEV₁ percent predicted (FEV₁ pp) for each study period was recorded. Respiratory culture results and sources (sputum versus OP) were noted as were the numbers of hospitalizations and exacerbations for both periods. Centers uploaded their results into a shared Excel file without patient identifiers. Statistical analysis was completed at the Pediatric Center at the University of Tennessee, Memphis, Tennessee, using SAS 9.4 software (SAS Institute, Cary, NC).

Results: Forty pediatric and adult CF patients are included in this analysis. For this small sample, FEV₁ pp improved significantly after starting ETI therapy. More OP than sputum samples were collected post ETI. Culture results for Staphylococcus aureus (methicillin sensitive and methicillin resistant) were similar for both periods but fewer patients were culture positive for Pseudomonas aeruginosa post modulator therapy. Four patients grew Burkholderia cepacia, and 7 had Stenotrophomonas before therapy - all were culture negative after starting ETI. Fewer hospitalizations and exacerbations were noted post therapy. Data are summarized in the table attached.

Conclusions: We noted improved FEV₁ pp post ETI. Miller et al⁵ showed fewer overall healthcare visits, inpatient stays, and fewer sick visits in the year after starting high quality modulator therapy. Our data support this observation and confirmed that significantly fewer sputum samples were collected post ETI. Although the Consortium has 5 CF Care Centers, only a few patients from each Center are included in this preliminary analysis. Future steps for the Tennessee and Mississippi Consortium include analysis of the full patient population in the period immediately prior to approval of ETI and the period following ETI to further determine the effects of ETI as well as the pandemic on observed CF outcomes. Culture positivity for acid fast bacilli will be assessed. Data for pediatric CF patients will be compared to adults with cystic fibrosis.

Acknowledgements: CF Center Registry Coordinators for Tennessee and Mississippi
Rumana Siddique, PhD: Statistician, Memphis, TN

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