Changes in LCI in F508del/F508del patients treated with lumacaftor/ivacaftor: Results from the prospect study.

The PROSPECT study, a post-approval observational study in the U.S., showed no significant changes in lung function as measured by spirometry with clinical initiation of lumacaftor/ivacaftor. A sub-study within the PROSPECT study assessed the lung clearance index (LCI), as measured by multiple breath washout (MBW), a measure of lung function demonstrated to be sensitive among people with normal spirometry. Participants performed MBW prior to clinically initiating lumacaftor/ivacaftor therapy and for one year of follow-up. Similar to the whole PROSPECT study, this sub-study cohort (N = 49) had no significant absolute or relative changes in FEV ₁ % predicted at any time point. LCI, however, decreased (improved) by 0.81 units or 5.3% (95% CI -9.7, -0.9%) at 1 month, 0.77 units or 5.9% at 3 months, 0.67 units or 5.9% at 6 months, and 0.55 units or 4.3% at 12 months. These results demonstrate the utility of the LCI in assessing treatment effects of relatively modest size in a heterogenous study population.
Competing Interests: Declaration of Competing Interest MS has nothing to disclose. UK reports grants from Cystic Fibrosis Foundation, during the conduct of the study and outside the submitted work. JPC reports grants from Cystic Fibrosis Foundation, during the conduct of the study. SHD reports grants from Cystic Fibrosis Foundation, during the conduct of the study. SDS reports a grant from the Cystic Fibrosis Foundation that funds the work under consideration, and grants from the Cystic Fibrosis Foundation and National Institutes of Health funding activities outside the submitted work. SMR reports grants, contracts, and consulting services from Vertex Pharmaceuticals related to the conduct of clinical trials. FR reports grants and personal fees from Vertex, personal fees from Novartis, personal fees from Bayer, personal fees from Roche, personal fees from Genetech, outside the submitted work.
(Copyright © 2020. Published by Elsevier B.V.)