Original Research |

Effects of Ivacaftor in cystic fibrosis patients carrying the G551D mutation with severe lung disease

Peter J. Barry, MB, Bch, BAO; Barry J. Plant, MD; Arjun Nair, MB, ChB; Stephen Bicknell, MB, ChB; Nicholas J. Simmonds, MD; Nicholas J. Bell, MRCP; Nadia T. Shafi, MD; Thomas Daniels, MD; Susan Shelmerdine, MBBS; Imogen Felton, MRCP; Cedric Gunaratnam, MRCP; Andrew M. Jones, MD; Alex R. Horsley, PhD
Author and Funding Information

University Hospital of South Manchester, Manchester, United Kingdom (Barry, Jones, Horsley); Royal College of Physicians of Ireland, Dublin, Ireland (Barry); Cork University Hospital, University College Cork, Cork, Ireland (Plant); Royal Brompton Hospital and Imperial College, London, United Kingdom (Nair, Simmonds, Shelmerdine, Felton); Gartnavel General Hospital, Glasgow, United Kingdom (Bicknell); Bristol Adult Cystic Fibrosis Centre, Bristol, United Kingdom (Bell); Papworth Hospital, Cambridge, United Kingdom (Shafi); University Hospital Southampton, Southampton, United Kingdom (Daniels); Beaumont Hospital, Dublin, Ireland (Gunaratnam); The University of Manchester, Manchester Academic Health Science Centre, University Hospital South Manchester NHS Foundation Trust, Manchester, UK (Jones, Horsley)

Corresponding author: Alex Horsley, PhD, Senior Lecturer and Honorary Consultant, Manchester Adult Cystic Fibrosis Unit, University Hospital of South Manchester, Wythenshawe, M23 9LT, United Kingdom; E-mail: alexander.horsley@manchester.ac.uk

Funding Information: This study was supported by the Manchester Adult Cystic Fibrosis Centre. No financial support, involvement or editorial input of any sort was sought or received from Vertex pharmaceuticals. Dr Horsley is funded by a National Institute for Health Research Clinician Scientist award. This report presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

Chest. 2014. doi:10.1378/chest.13-2397
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Background  The development of ivacaftor represents a significant advance in therapeutics for cystic fibrosis (CF) patients with the G551D mutation. Patients with an FEV1<40% predicted represent a significant proportion of eligible patients but were excluded from phase III clinical trials and the effectiveness of the drug in this population is therefore unknown.

Methods  Data were collected from adult CF centres in the UK and Ireland with patients enrolled in an ivacaftor compassionate use programme (FEV1<40% or on lung transplant waiting list). Clinically recorded data were collated from patient records for 1 year prior, and for a period of 90 to 270 days following ivacaftor commencement. Each patient was matched with up to two controls who would have met the requirements for the compassionate use programme with the exception of genotype.

Results  21 patients received ivacaftor for a median of 237 days. Mean FEV1 improved from 26·5% to 30·7% predicted (p=0·01), representing a 16.7% relative improvement. Median weight improved from 49·8 to 51·6kg (p=0·006). Median in-patient intravenous antibiotic days declined from 23 to 0 days per year (p=0.001) and median total intravenous treatment days decreased from 74 to 38 days per year (p=0.002) following ivacaftor. Changes in pulmonary function and intravenous antibiotic requirements were significant compared to control subjects.

Conclusions  Ivacaftor was clinically effective in CF patients carrying the G551D mutation with severe pulmonary disease. The reductions in treatment requirements were clinically and statistically significant and have not been described in less severe populations.

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