320 The use of ivacaftor in CF mutations with residual functioning protein

Abstract

Objectives Ivacaftor was shown to decrease FEV1 by 5% in patients with classIV R117H mutation. We report the use of ivacaftor in four CF adults with various Class IV mutations. Methods Ivacaftor was prescribed to 4 patients with deteriorating clinical status. We obtained pre and post administration FEV1, weight, sweat chloride (in 3/4), and CFQ-R. Results Patient 1, a 26yo woman, CF genotype of 2 class IV mutations (R347P & L1065P). She had four pulmonary exacerbations, FEV1 dropped from 85% to 75%. Six months following ivacaftor, FEV1 improved to 81%. She gained 10 lbs. Sweat chloride decreased from 96 to 86 mmol/L and CFQ-R increased from 55 to 100. Discontinuation of ivacaftor showed marked worsening in all parameters. Patient 2 is a 61yo male with W1282X and the class IV mutation D1152H. Six months into ivacaftor, FEV1 improved from 67% to 87% and he gained 17 lbs. Sweat chloride decreased from 30 to 22 mmol/L and CFQ-R improved from 55 to 100 points. Patient 3 is a 35yo male with the class IV D579G mutation and S912X. After ivacaftor, FEV1 improved from 27% to 31%. He gained 7 lbs. Sweat chloride decreased from 91 to 74 mmol/L and CFQ-R doubled. Patient 4 is a 72yo male with CF genotype G542X and the class IV mutation D1152H. Following ivacaftor, FEV1 improved from 39% to 51%. He gained 7 lbs and CFQ-R doubled. Conclusion We noted improvement in all patients and in all parameters at 6 months compared to baseline. One patient was retested at one month after stopping ivacaftor with worsening parameters. These data support the beneficial effects of CFTR potentiators in CF mutations producing residual functioning protein.