152 Original Research [ 146#1 CHEST JULY 2014 ] Efects of Ivacafor in Patients With Cystic Fibrosis Who Carry the G551D Mutation and Have Severe Lung Disease Peter J. Barry, MBBCh; Barry J. Plant, MD; Arjun Nair , MBChB; Stephen Bicknell, MBChB; Nicholas J. Simmonds, MD; Nicholas J. Bell, MBChB; Nadia T. Shafi , MD; Thomas Daniels, MD; Susan Shelmerdine, MBBS; Imogen Felton, MBBS; Cedric Gunaratnam MBBCh; Andrew M. Jones, MD; and Alex R. Horsley, PhD BACKGROUND: Te development of ivacafor represents a signifcant advance in therapeutics for patients with cystic fbrosis (CF) who carry the G551D mutation. Patients with an FEV 1 , 40% predicted represent a considerable proportion of eligible patients but were excluded from phase 3 clinical trials, and the efectiveness of the drug in this population is, therefore, unknown. METHODS: Data were collected from adult CF centers in the United Kingdom and Ireland with patients enrolled in an ivacafor compassionate use program (FEV 1 , 40% or on lung trans- plant waiting list). Clinically recorded data were collated from patient records for 1 year prior and for a period of 90 to 270 days following ivacafor commencement. Each patient was matched to two control subjects who would have met the requirements for the compassionate use program with the exception of genotype. RESULTS: Twenty-one patients received ivacafor for a median of 237 days. Mean FEV 1 improved from 26.5% to 30.7% predicted ( P 5 .01), representing a 16.7% relative improve- ment. Median weight improved from 49.8 to 51.6 kg ( P 5 .006). Median inpatient IV antibiotic days declined from 23 to 0 d/y ( P 5 .001) and median total IV treatment days decreased from 74 to 38 d/y ( P 5 .002) following ivacafor. Changes in pulmonary function and IV antibiotic requirements were signifcant compared with control subjects. CONCLUSIONS: Ivacaftor was clinically effective in patients with CF who carry the G551D mutation and have severe pulmonary disease. Te reductions in treatment requirements were clinically and statistically signifcant and have not been described in less severe populations. CHEST 2014; 146(1):152-158 [ Original Research Genetic and Developmental Disorders ] Manuscript received October 8, 2013; revision accepted January 2, 2014; originally published Online First February 13, 2014. ABBREVIATIONS: CF 5 cystic fbrosis AFFILIATIONS: From the University Hospital of South Manchester NHS Foundation Trust (Drs Barry, Jones, and Horsley), Manchester, England; Royal College of Physicians of Ireland (Dr Barry), Dublin, Ireland; Cork University Hospital (Dr Plant), University College Cork, Cork, Ireland; Royal Brompton Hospital and Imperial College (Drs Nair, Simmonds, Shelmerdine, and Felton), London, England; Gartnavel General Hospital (Dr Bicknell), Glasgow, Scotland; Bristol Adult Cystic Fibrosis Centre (Dr Bell), Bristol, England; Papworth Hospital (Dr Shaf), Cambridge, England; University Hospital South- ampton (Dr Daniels), Southampton, England; Beaumont Hospital (Dr Gunaratnam), Dublin, Ireland; and the University of Manchester, Manchester Academic Health Science Centre (Dr Horsley), University Hospital of South Manchester NHS Foundation Trust, Manchester, England. FUNDING/SUPPORT: Tis study was supported by the Manchester Adult Cystic Fibrosis Centre. Dr Horsley is funded by a National Institute for Health Research Clinician Scientist award [NIHR CS012-013]. Some of the data included in this manuscript have been published in abstract form (Barry P, Plant B, Nair A, et al. J Cyst Fibros. 2013;12[1]:S15 and Barry P, Plant B, Simmonds NJ, et al. J Cyst Fibros. 2013;12[1]:S62) and presented at the European Cystic Fibrosis Conference, June 12-15, 2013, Lisbon, Portugal, and at the North American Cystic Fibrosis Conference, October 17-19, 2013, Salt Lake City, UT. CORRESPONDENCE TO: Alex R. Horsley, PhD, Manchester Adult Cystic Fibrosis Center, University Hospital of South Manchester, Wythenshawe, Manchester, M23 9LT, England; e-mail: alexander.horsley@manchester. ac.uk © 2014 AMERICAN COLLEGE OF CHEST PHYSICIANS. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.13-2397 Downloaded From: http://journal.publications.chestnet.org/ on 12/02/2015