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Observational Study
. 2019 Jan;18(1):102-109.
doi: 10.1016/j.jcf.2018.04.004. Epub 2018 Apr 21.

Effectiveness of ivacaftor in cystic fibrosis patients with non-G551D gating mutations

Jennifer Guimbellot  1 , George M Solomon  2 , Arthur Baines  3 , Sonya L Heltshe  4 , Jill VanDalfsen  3 , Elizabeth Joseloff  5 , Scott D Sagel  6 , Steven M Rowe  7 ; GOALe(2) Investigators
Affiliations
Observational Study

Effectiveness of ivacaftor in cystic fibrosis patients with non-G551D gating mutations

Jennifer Guimbellot et al. J Cyst Fibros. 2019 Jan.

Abstract

Background: The cystic fibrosis transmembrane conductance regulator (CFTR) potentiator ivacaftor is approved for patients with CF with gating and residual function CFTR mutations. We report the results of an observational study investigating its effects in CF patients with non-G551D gating mutations.

Methods: Patients with non-G551D gating mutations were recruited to an open-label study evaluating ivacaftor. Primary outcomes included: lung function, sweat chloride, weight gain, and quality of life scores.

Results: Twenty-one subjects were enrolled and completed 6 months follow-up on ivacaftor; mean age was 25.6 years with 52% <18. Baseline ppFEV1 was 68% and mean sweat chloride 89.6 mEq/L. Participants experienced significant improvements in ppFEV1 (mean absolute increase of 10.9% 95% CI = [2.6,19.3], p = 0.0134), sweat chloride (-48.6 95% CI = [-67.4,-29.9], p < 0.0001), and weight (5.1 kg, 95% CI = [2.8, 7.3], p = 0.0002).

Conclusions: Patients with non-G551D gating mutations experienced improved lung function, nutritional status, and quality of life. This study supports ongoing use of ivacaftor for patients with these mutations.

Keywords: CFTR potentiator; Clinical trials; Gating mutation; Ivacaftor.

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Conflict of interest statement

CONFLICTS OF INTEREST

SMR serves as an investigator and consultant to Vertex Pharmaceuticals, the manufacturer of ivacaftor, on the design and conduct of CF clinical trials. GMS serves as an investigator on studies conducted by Vertex Pharmaceuticals.

Figures

Figure 1
Figure 1
Trial Consort Diagram
Figure 2
Figure 2. Mean change from baseline after 6 months of treatment
(A) percent predicted FEV1; (B) BMI; (C) sweat chloride; and (D) CFQ-R respiratory score. ppFEV1 (percent predicted FEV1); BMI (body mass index); CFQ-R (Cystic Fibrosis Questionnaire-Revised)
Figure 3
Figure 3. Hospitalization Rates and P. Aeruginosa Isolation
Data was extracted from CFF Patient Registry for the subjects in the time period 12 months before initiation of ivacaftor and in the time period after initiation of ivacaftor. (A) Percent of subjects hospitalized in the indicated time periods; (B) Percent of subjects with P. Aeruginosa (PA) in the indicated time period.
See this image and copyright information in PMC

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