Jennifer Guimbellot1, George M Solomon2, Arthur Baines3, Sonya L Heltshe4, Jill VanDalfsen3, Elizabeth Joseloff5, Scott D Sagel6, Steven M Rowe7. 1. Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham (UAB), Birmingham, AL, USA; Department of Pediatrics, Division of Pulmonary and Sleep Medicine, UAB, Birmingham, AL, USA. 2. Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham (UAB), Birmingham, AL, USA; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, UAB, Birmingham, AL, USA. 3. CFF Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle 98105, WA, USA. 4. CFF Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle 98105, WA, USA; Department of Pediatrics, Division of Pulmonary and Sleep Medicine, University of Washington, Seattle, WA, USA. 5. Cystic Fibrosis Foundation, Bethesda, MD, USA. 6. Department of Pediatrics, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA. 7. Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham (UAB), Birmingham, AL, USA; Department of Pediatrics, Division of Pulmonary and Sleep Medicine, UAB, Birmingham, AL, USA; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, UAB, Birmingham, AL, USA. Electronic address: smrowe@uab.edu.
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.
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 CFpatients 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.
Authors: Michael S Stalvey; Jesse Pace; Minoo Niknian; Mark N Higgins; Valerie Tarn; Joy Davis; Sonya L Heltshe; Steven M Rowe Journal: Pediatrics Date: 2017-02 Impact factor: 7.124
Authors: Edward F McKone; Drucy Borowitz; Pavel Drevinek; Matthias Griese; Michael W Konstan; Claire Wainwright; Felix Ratjen; Isabelle Sermet-Gaudelus; Barry Plant; Anne Munck; Ying Jiang; Geoffrey Gilmartin; Jane C Davies Journal: Lancet Respir Med Date: 2014-10-09 Impact factor: 30.700
Authors: Kerstin Pohl; Elaine Hayes; Joanne Keenan; Michael Henry; Paula Meleady; Kevin Molloy; Bakr Jundi; David A Bergin; Cormac McCarthy; Oliver J McElvaney; Michelle M White; Martin Clynes; Emer P Reeves; Noel G McElvaney Journal: Blood Date: 2014-06-16 Impact factor: 22.113
Authors: Sanja Stanojevic; Stephanie D Davis; George Retsch-Bogart; Hailey Webster; Miriam Davis; Robin C Johnson; Renee Jensen; Maria Ester Pizarro; Mica Kane; Charles C Clem; Leah Schornick; Padmaja Subbarao; Felix A Ratjen Journal: Am J Respir Crit Care Med Date: 2017-05-01 Impact factor: 21.405
Authors: Jane C Davies; Claire E Wainwright; Gerard J Canny; Mark A Chilvers; Michelle S Howenstine; Anne Munck; Jochen G Mainz; Sally Rodriguez; Haihong Li; Karl Yen; Claudia L Ordoñez; Richard Ahrens Journal: Am J Respir Crit Care Med Date: 2013-06-01 Impact factor: 21.405
Authors: Jane C Davies; Steve Cunningham; William T Harris; Allen Lapey; Warren E Regelmann; Gregory S Sawicki; Kevin W Southern; Sarah Robertson; Yulia Green; Jon Cooke; Margaret Rosenfeld Journal: Lancet Respir Med Date: 2016-01-21 Impact factor: 30.700
Authors: Frank J Accurso; Fredrick Van Goor; Jiuhong Zha; Anne J Stone; Qunming Dong; Claudia L Ordonez; Steven M Rowe; John Paul Clancy; Michael W Konstan; Heather E Hoch; Sonya L Heltshe; Bonnie W Ramsey; Preston W Campbell; Melissa A Ashlock Journal: J Cyst Fibros Date: 2014-03 Impact factor: 5.527
Authors: Scott D Sagel; Umer Khan; Sonya L Heltshe; John P Clancy; Drucy Borowitz; Daniel Gelfond; Scott H Donaldson; Antoinette Moran; Felix Ratjen; Jill M VanDalfsen; Steven M Rowe Journal: Ann Am Thorac Soc Date: 2021-01