Clinical change 2 years from start of elexacaftor‐tezacaftor‐ivacaftor in severe cystic fibrosis

Abstract

Rationale Limited published research is available on the impact of elexacaftor/tezacaftor/ivacaftor (ETI) beyond the initial few months postdrug initiation, especially for those who initiated therapy via individual investigational new drug application. The experiences of patients with cystic fibrosis (CF) experiencing severe lung disease were reviewed for significant improvements in clinical symptoms and quality of life. Objectives To examine clinical outcomes 2 years post‐ETI in patients with CF and advanced lung disease. Methods This single center institutional review board‐approved, retrospective chart review assessed clinical markers (percent predicted forced expiratory volume in 1 s, weight, sweat chloride), quality of life and computed tomography scans in patients with advanced lung disease who met criteria for compassionate use/expanded access program due to high risk of death or transplant need within 2 years. Results Eighteen identified patients (ages 15−49 years) initiated drug between July and September 2019. Clinical markers indicated that therapy was well tolerated, not discontinued by any participant, and lab values did not indicate medical concern or discontinuation. Monitoring results indicated the safety of modulator therapy as there were no adverse clinical occurrences and all patients presented universal stabilization. There were no deaths and no transplants by the end of the study. Conclusions This study focused on patients with CF eligible for modulator therapy and were initiated due to advanced lung disease. Initiation of modulator therapy was deemed safe and resulted in objective positive changes in nutrition, cough, FEV1, subjective reports of clinical status, level of activity, and a reduction in burden of treatment.

Radiological and long‐term clinical response to elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with advanced lung disease

“…Just as in our study, they described all patients reaching clinical stability while the drug was well tolerated. 13 Inclusion criteria for both phase III trials for ELE/TEZ/IVA included ppFEV 1 above 40, so that the studied groups are not easily comparable to ours. For effects on FEV 1 , both the trial including homozygous F508del pwCF and the one including F508del/MF pwCF found a larger difference after initiation of the treatment compared to the increase in our study.…”

Evolving nutritional needs, obesity, and overweight status in cystic fibrosis

“…This suggests potential contribution from altered metabolism, energy balance and energy expenditure. Among those with severe lung disease, similar positive impacts have been noted in lung function, quality of life and BMI [11 ▪ ,12].…”

Elexacaftor-Tezacaftor-Ivacaftor: A Life-Changing Triple Combination of CFTR Modulator Drugs for Cystic Fibrosis

“…McCoy and collaborators retrospectively assessed various clinical parameters, such as ppFEV 1 , BMI, SCC, and QoL, in a two-year post-ETI period in 18 PwCF (aged 15–49 years) with advanced lung disease [ 56 ]. Overall, ETI therapy was well-tolerated, and no participant discontinued it in the two-year follow-up period.…”

“…There were no new safety concerns, and no participant required a lung transplant over the follow-up period. Regarding efficacy, data demonstrated a sustained improvement in clinical outcomes, including lung function, nutritional status, and respiratory symptoms, which resulted in a reduction in therapy burden and, consequently, a better quality of life for PwCF [ 56 ].…”