Chest
Volume 146, Issue 1, July 2014, Pages 152-158
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Original Research
Genetic And Developmental Disorders
Effects of Ivacaftor in Patients With Cystic Fibrosis Who Carry the G551D Mutation and Have Severe Lung Disease

https://doi.org/10.1378/chest.13-2397Get rights and content

BACKGROUND

The development of ivacaftor represents a significant advance in therapeutics for patients with cystic fibrosis (CF) who carry the G551D mutation. Patients with an FEV1 < 40% predicted represent a considerable proportion of eligible patients but were excluded from phase 3 clinical trials, and the effectiveness 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 ivacaftor compassionate use program (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 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 ivacaftor for a median of 237 days. Mean FEV1 improved from 26.5% to 30.7% predicted (P = .01), representing a 16.7% relative improvement. Median weight improved from 49.8 to 51.6 kg (P = .006). Median inpatient IV antibiotic days declined from 23 to 0 d/y (P = .001) and median total IV treatment days decreased from 74 to 38 d/y (P = .002) following ivacaftor. Changes in pulmonary function and IV antibiotic requirements were significant compared with control subjects.

CONCLUSIONS

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

Section snippets

Materials and Methods

We conducted a retrospective case-control study of patients receiving ivacaftor on the compassionate use program in the United Kingdom and Ireland. All centers with adult patients enrolled into this program were contacted to participate in the study.

Results

Data were collected on 21 patients with severe CF lung disease who received ivacaftor (composing 84% of the eligible adult patients in the United Kingdom and Ireland receiving ivacaftor under the compassionate use program) and 35 matched control subjects who did not carry the G551D mutation. Follow-up data were available for a median of 237 days (range, 125-270 days) after ivacaftor commencement.

Baseline demographics of the study population are contained in Table 1 and e-Table 2. Absolute

Discussion

In patients with CF who carry the G551D mutation and have severe pulmonary disease, provision of ivacaftor led to significant improvements in FEV1 and FVC and improvements in weight and BMI. In addition, we have also shown a significant and clinically important reduction in the number of IV treatment days.

The clinical efficacy of ivacaftor in patients with CF who carry the G551D mutation and have mild to moderate pulmonary disease has been established in two large, phase 3 clinical trials.6, 7

Acknowledgments

Author contributions: A. R. H. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. P. J. B. served as principal author. P. J. B., B. J. P., S. B., N. J. S., N. J. B., N. T. S., T. D., A. M. J., and A. R. H. contributed to the study design; P. J. B., B. J. P., A. N., S. B., N. J. S., N. J. B., N. T. S., T. D., S. S., I. F., C. G., and A. R. H. contributed to data acquisition; P. J. B. and A. R. H.

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FUNDING/SUPPORT: This 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.

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