Clinical improvement 2 years after starting elexacaftor/tezacaftor/ivacaftor in patients with advanced lung disease

ABSTRACT

Background: With the introduction of new cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy (elexacaftor/tezacaftor/ ivacaftor), peoplewith CF experiencing severe lung disease can experience significant improvements in clinical symptoms. Method(s) This single-center institutional review board-approved retrospective chart review identified patients with advanced lung disease who met criteria for a compassionate use or expanded access program because of high risk of death or transplant need within 2 years. Clinical data collection for all patients began at baseline, 2 to 4 weeks after therapy initiation, and continued every 3 months for 2 years. Datawere collected on demographic characteristics, clinic progress notes, clinical labs, forced expiratory volume in 1 minute (FEV1),weight, body mass index, respiratory colonization, and hospitalizations after drug initiation. Patients also completed sinus and chest computed tomography (CT) to track clinical changes. Result(s) Eighteen people with CF (aged 15-49, 56% male) from a large midwestern CF center who initiated drug therapy between July and September 2019 in an inpatient hospital or clinic setting were identified. Clinical markers (Table 1) indicated that modulator therapy was well tolerated and not discontinued by any participant;safety lab values did not indicate medical concern or discontinuation. There were 90 admissions for the group in the 2 years before therapy and 17 admissions during the 2 years after, although seven of the posttherapy admissions were for nonrespiratory indications. Monitoring results indicated the safety of modulator therapy because there were no adverse clinical occurrences or laboratory events, and all patients presented with universal stabilization. There have been no deaths and no transplants. Unlike lumacaftor/ivacaftor, therewere no problems with chest tightness or any difficulty with troublesome increases in expectoration burden or choking during initiation of therapy. Most had significant reduction in or loss of spontaneous cough and sputum production. The impact on microbial colonization is unclear, because even in this severe group, inability to produce sputum on command led to considerable missing data in follow-up, leaving colonization status at follow-up unclear. Conclusion(s) This study focused on people with CF who qualified for modulator therapy based on advanced lung disease. Initiation of modulator therapy was deemed safe and resulted in objective positive changes in nutrition;cough;FEV1);and subjective reports of clinical status, level of activity, and reduction in burden of treatment. No evidence was found of difficulty managing the increased expectoration during initial therapy. Limitations were noted in missing data during the COVID-19 pandemic, small sample size, and delayed follow-up for drug monitoring.(Table Presented) Clinical indicators before and after modulator therapy *Completed post-drug initiation (earlier than 12 months), **24 months before and after therapy initiationCopyright © 2022, European Cystic Fibrosis Society. All rights reserved