Clinical effect of lumacaftor/ivacaftor in F508del homozygous CF patients with FEV1 ≥ 90% predicted at baseline

Clinical response to lumacaftor-ivacaftor in patients with cystic fibrosis according to baseline lung function

“…This result is consistent with our previous report, which found that treatment discontinuation rate was higher in adults compared to younger patients [14]. In the subgroup of patients with ppFEV 1 ≥90, treatment with LUMA-IVA failed to significantly improve ppFEV 1 , confirming the results of Aalbers et al [13] .. However, our data extend these findings by showing that individual response was markedly heterogeneous, with some patients increasing their ppFEV 1 by more than 25% (see Fig.…”

“…The present analysis was not only obtained in larger numbers of patients compared to the study by Aalbers et al It was also obtained in a much diverse population that was followed in multiple centers and was predominantly composed of adults. Aalbers et al reported treatment discontinuation in only 2.5% of patients (1/40), which is markedly lower than in the present study [13] . This result is consistent with our previous report, which found that treatment discontinuation rate was higher in adults compared to younger patients [14].…”

“…In this subgroup of patients, the rate (17.5%) and causes of treatment discontinuation were comparable to those of patients with ppFEV 1 [40-90[. To the best of our knowledge only one other study, by Aalbers et al, evaluated the effects of LUMA-IVA over one year, but in a smaller cohort ( n = 40) of patients, who were younger (12 patients < 11 years, 13 adolescents, 14 adults) and followed at a single center [13] . The present analysis was not only obtained in larger numbers of patients compared to the study by Aalbers et al It was also obtained in a much diverse population that was followed in multiple centers and was predominantly composed of adults.…”

“…Several post-marketing studies have reported safety issues, mostly related to respiratory adverse events, in patients with ppFEV 1 < 40 [8][9][10] . However, few studies have examined the safety profile of LUMA-IVA in patients with ppFEV 1 ≥90 or its benefits for those with ppFEV 1 < 40 [ 11 , 12 ] or ppFEV 1 ≥90 [13] . Furthermore these studies generally included a limited number of patients from a small number of centers, who were not compared to patients with FEV 1 [40-90[in terms of effect magnitude. The present study used data collected during a previously published real world study conducted in France, which followed a large cohort of patients aged 12 years and older who started LUMA-IVA in 2016 [14], in order to examine its safety and effectiveness at different levels of baseline ppFEV 1 over the first year of treatment.…”

In Silico Molecular Dynamics Docking of Drugs to the Inhibitory Active Site of SARS-CoV-2 Protease and Their Predicted Toxicology and ADME

“…Trametinib (Rank 108, BE=-8.4, B08911) is indicated for the treatment of unresectable or metastatic melanoma [107] , advanced rectal [111] , breast [112] , biliary [113] , colorectal, non-small cell lung, and pancreatic cancer [114] . Lumacaftor (Rank 117, BE=-8.4, B09280) is indicated for the treatment of cystic fibrosis (CF) in patients age 6 years and older who are homozygous for the F508del mutation in the CFTR gene [115][116][117] . Ergotamine (Rank 154, BE=-8.3, B00696) is for use as therapy to abort or prevent vascular headache, e.g., migraine, migraine variants, or so called "histaminic cephalalgia" [118][119][120] .…”