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

Background: With the introduction of the new CFTR modulator therapy (elexacaftor/tezacaftor/ivacaftor), patients with cystic fibrosis experiencing severe lung disease were offered an opportunity to experience significant improvements in clinical symptoms.

Methods: This single center IRB-approved retrospective chart review identified patients with advanced lung disease who met criteria for compassionate use/expanded access program due to high risk of death or transplant need within two years. Clinical data collection for all patients began at baseline, 2-4 weeks after therapy initiation and continued every 3 months for two years. Data queried includes demographics, clinic progress notes, clinical labs, FEV1, Weight, BMI, respiratory colonization, and hospitalizations following drug initiation. Patients also completed sinus CT and chest CT in order to track clinical changes.

Results: Eighteen patients with CF (ages = 15-49 years, 56% male) from a large mid-western CF center were identified. They initiated drug between July and September 2019 in an inpatient hospital or clinic setting. Clinical markers (see Table 1) indicated that modulator therapy was well tolerated, not discontinued by any participant, and safety lab values did not indicate medical concern or discontinuation. There were 90 admissions for the group the two years prior to therapy and 17 admissions during the two years post, however seven of the post admissions were for non-respiratory indications. Monitoring results indicated the safety of modulator therapy as there were no adverse clinical occurrences or laboratory events and all patients presented universal stabilization. There were no deaths and no transplants to date.

Unlike lumacaftor/ivacaftor there were no problems with chest tightness, nor any difficulty with troublesome increases in expectoration burden or choking during initiation of drug. The majority had significant reduction in or loss of spontaneous cough as well as sputum production. The impact on microbial colonization is unclear, since even in this severe group the inability to produce sputum on command led to lots of missing data in follow-up, leaving the colonization status at follow-up still unclear.

Conclusions: This study focused on patients 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 a reduction in burden of treatment. No evidence was found for difficulty in handling the increased expectoration during initial therapy. Limitations were noted in missing data during world-wide pandemic, small sample size and delayed follow-up for drug monitoring.

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