Effects of lumacaftor-ivacaftor therapy on cystic fibrosis transmembrane conductance regulator function in Phe508del homozygous patients with cystic fibrosis

American Journal of Respiratory and Critical Care Medicine

Volumn 197, Issue 11, 2018, Pages 1433-1442

  Graeber, Simon Y ^a,b   Dopfer, Christian ^c   Naehrlich, Lutz ^d,e   Gyulumyan, Lena ^c   Scheuermann, Heike ^a   Hirtz, Stephanie ^a   Wege, Sabine ^f   Mairbäurl, Heimo ^a,f,g   Dorda, Marie ^c   Hyde, Rebecca ^c   Bagheri Hanson, Azadeh ^d   Rueckes Nilges, Claudia ^d,e   Fischer, Sebastian ^c   Mall, Marcus A ^a   Tümmler, Burkhard ^c  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^c HANNOVER MEDICAL SCHOOL   (Germany)

^d JUSTUS LIEBIG UNIVERSITY GIESSEN   (Germany)

^e JUSTUS LIEBIG UNIVERSITY GIESSEN   (Germany)

^f UNIVERSITY OF HEIDELBERG   (Germany)

^g UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

Author keywords

Cystic fibrosis; Cystic fibrosis transmembrane conductance regulator biomarker; Intestinal current measurement; Nasal potential difference; Sweat test

Indexed keywords

CHLORIDE; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; IVACAFTOR; LUMACAFTOR; 1,3 BENZODIOXOLE DERIVATIVE; AMINOPHENOL DERIVATIVE; AMINOPYRIDINE DERIVATIVE; BIOLOGICAL MARKER; CHLORIDE CHANNEL STIMULATING AGENT; LUMACAFTOR, IVACAFTOR DRUG COMBINATION; QUINOLONE DERIVATIVE;

ADOLESCENT; ADULT; AGE; AIRWAY; ARTICLE; BODY MASS; CHILD; CLINICAL OUTCOME; CONTROLLED STUDY; CYSTIC FIBROSIS; DRUG EFFECT; DRUG EFFICACY; EXPIRATORY FLOW; FEMALE; FOLLOW UP; FORCED EXPIRATORY VOLUME; GENE MUTATION; HUMAN; IN VIVO STUDY; INTESTINE; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NOSE EPITHELIUM; OBSERVATIONAL STUDY; ORGAN SYSTEMS; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; PROSPECTIVE STUDY; RECTUM EPITHELIUM; SWEAT; TREATMENT RESPONSE; VITAL CAPACITY; BLOOD; DRUG COMBINATION; GENETICS; GERMANY; HOMOZYGOTE; YOUNG ADULT;

ADOLESCENT; ADULT; AMINOPHENOLS; AMINOPYRIDINES; BENZODIOXOLES; BIOMARKERS; CHILD; CHLORIDE CHANNEL AGONISTS; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; DRUG COMBINATIONS; FEMALE; GERMANY; HOMOZYGOTE; HUMANS; MALE; PROSPECTIVE STUDIES; QUINOLONES; YOUNG ADULT;

EID: 85048067969     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201710-1983OC     Document Type: Article

References (48)

1. Elborn JS. Cystic fibrosis. Lancet 2016;388:2519-2531.
2. Ratjen F, Bell SC, Rowe SM, Goss CH, Quittner AL, Bush A. Cystic fibrosis. Nat Rev Dis Primers 2015;1:15010.
3. Mall MA, Hartl D. CFTR: cystic fibrosis and beyond. Eur Respir J 2014; 44:1042-1054.
4. Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, et al.; TRAFFIC Study Group; TRANSPORT Study Group. Lumacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR. N Engl J Med 2015;373:220-231.
5. Konstan MW, McKone EF, Moss RB, Marigowda G, Tian S, Waltz D, et al. Assessment of safety and efficacy of long-term treatment with combination lumacaftor and ivacaftor therapy in patients with cystic fibrosis homozygous for the F508del-CFTR mutation (PROGRESS): a phase 3, extension study. Lancet Respir Med 2017; 5:107-118.
6. Boyle MP, Bell SC, Konstan MW, McColley SA, Rowe SM, Rietschel E, et al.; VX09-809-102 Study Group. A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a Phe508del CFTR mutation: a phase 2 randomised controlled trial. Lancet Respir Med 2014;2:527-538.
7. Ratjen F, Hug C, Marigowda G, Tian S, Huang X, Stanojevic S, et al.; VX14-809-109 Investigator Group. Efficacy and safety of lumacaftor and ivacaftor in patients aged 6-11 years with cystic fibrosis homozygous for F508del-CFTR: a randomised, placebo-controlled phase 3 trial. Lancet Respir Med 2017;5:557-567.
8. Accurso FJ, Rowe SM, Clancy JP, Boyle MP, Dunitz JM, Durie PR, et al. Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med 2010;363: 1991-2003.
9. Graeber SY, Hug MJ, Sommerburg O, Hirtz S, Hentschel J, Heinzmann A, et al. Intestinal current measurements detect activation of mutant CFTR in patients with cystic fibrosis with the G551D mutation treated with ivacaftor. Am J Respir Crit Care Med 2015;192:1252-1255.
10. Seeger W, Welte T, Eickelberg O, Mall M, Rabe KF, Keller B, et al. [The German Center for Lung Research: translational research for the prevention, diagnosis and treatment of respiratory diseases] [article in German]. Pneumologie 2012;66:464-469.
11. Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, et al.; ERS Global Lung Function Initiative. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J 2012;40:1324-1343.
12. Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, et al.; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J 2005;26:319-338.
13. Clinical and Laboratory Standards Institute. Sweat testing: sample collection and quantitative chloride analysis; approved guideline, 3rd ed. CLSI document C34-A3. Wayne, PA: Clinical and Laboratory Standards Institute; 2009.
14. Rowe SM, Clancy JP, Wilschanski M. Nasal potential difference measurements to assess CFTR ion channel activity. Methods Mol Biol 2011;741:69-86.
15. Rowe SM, Liu B, Hill A, Hathorne H, Cohen M, Beamer JR, et al.; VX06-770-101 Study Group. Optimizing nasal potential difference analysis for CFTR modulator development: assessment of ivacaftor in CF subjects with the G551D-CFTR mutation. PLoS One 2013;8:e66955.
16. Sermet-Gaudelus I, Girodon E, Sands D, Stremmler N, Vavrova V, Deneuville E, et al. Clinical phenotype and genotype of children with borderline sweat test and abnormal nasal epithelial chloride transport. Am J Respir Crit Care Med 2010;182:929-936.
17. Milla CE, Ratjen F, Marigowda G, Liu F, Waltz D, Rosenfeld M; VX13-809-011 Part B Investigator Group. Lumacaftor/ivacaftor in patients aged 6-11 years with cystic fibrosis and homozygous for F508del-CFTR. Am J Respir Crit Care Med 2017;195:912-920.
18. Solomon GM, Liu B, Sermet-Gaudelus I, Fajac I, Wilschanski M, Vermeulen F, et al. A multiple reader scoring system for nasal potential difference parameters. J Cyst Fibros 2017;16:573-578.
19. Accurso FJ, Van Goor F, Zha J, Stone AJ, Dong Q, Ordonez CL, et al. Sweat chloride as a biomarker of CFTR activity: proof of concept and ivacaftor clinical trial data. J Cyst Fibros 2014;13:139-147.
20. - channel function in native human colon correlates with the genotype and phenotype in cystic fibrosis. Gastroenterology 2004; 127:1085-1095.
21. Bronsveld I, Mekus F, Bijman J, Ballmann M, Greipel J, Hundrieser J, et al.; European CF Twin and Sibling Study Consortium. Residual chloride secretion in intestinal tissue of DF508 homozygous twins and siblings with cystic fibrosis. Gastroenterology 2000;119:32-40.
22. Mall M, Kreda SM, Mengos A, Jensen TJ, Hirtz S, Seydewitz HH, et al. The DF508 mutation results in loss of CFTR function and mature protein in native human colon. Gastroenterology 2004;126:32-41.
23. Veeze HJ, Sinaasappel M, Bijman J, Bouquet J, de Jonge HR. Ion transport abnormalities in rectal suction biopsies from children with cystic fibrosis. Gastroenterology 1991;101:398-403.
24. Ma T, Thiagarajah JR, Yang H, Sonawane ND, Folli C, Galietta LJ, et al. Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin-induced intestinal fluid secretion. J Clin Invest 2002;110:1651-1658.
25. Reddy MM, Quinton PM. Bumetanide blocks CFTR GCl in the native sweat duct. Am J Physiol 1999;276:C231-C237.
26. 1 channel opener 1-EBIO potentiates residual function of mutant CFTR in rectal biopsies from cystic fibrosis patients. PLoS One 2011; 6:e24445.
27. Clancy JP, Szczesniak RD, Ashlock MA, Ernst SE, Fan L, Hornick DB, et al. Multicenter intestinal current measurements in rectal biopsies from CF and non-CF subjects to monitor CFTR function. PLoS One 2013;8:e73905.
28. Heltshe SL, Cogen J, Ramos KJ, Goss CH. Cystic fibrosis: the dawn of a new therapeutic era. Am J Respir Crit Care Med 2017;195: 979-984.
29. Ramsey BW, Welsh MJ. AJRCCM: 100-year anniversary: progress along the pathway of discovery leading to treatment and cure of cystic fibrosis. Am J Respir Crit Care Med 2017;195:1092-1099.
30. Van Goor F, Hadida S, Grootenhuis PD, Burton B, Stack JH, Straley KS, et al. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci USA 2011;108:18843-18848.
31. Stanke F, Ballmann M, Bronsveld I, Dörk T, Gallati S, Laabs U, et al. Diversity of the basic defect of homozygous CFTR mutation genotypes in humans. J Med Genet 2008;45:47-54.
32. Derichs N, Sanz J, Von Kanel T, Stolpe C, Zapf A, Tümmler B, et al. Intestinal current measurement for diagnostic classification of patients with questionable cystic fibrosis: validation and reference data. Thorax 2010;65:594-599.
33. Wilschanski M, Dupuis A, Ellis L, Jarvi K, Zielenski J, Tullis E, et al. Mutations in the cystic fibrosis transmembrane regulator gene and in vivo transepithelial potentials. Am J Respir Crit Care Med 2006; 174:787-794.
34. Ranganathan SC, Hall GL, Sly PD, Stick SM, Douglas TA; Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST-CF). Early lung disease in infants and preschool children with cystic fibrosis: what have we learned and what should we do about it? Am J Respir Crit Care Med 2017;195:1567-1575.
35. Stahl M, Wielpütz MO, Graeber SY, Joachim C, Sommerburg O, Kauczor HU, et al. Comparison of lung clearance index and magnetic resonance imaging for assessment of lung disease in children with cystic fibrosis. Am J Respir Crit Care Med 2017;195:349-359.
36. Stanojevic S, Davis SD, Retsch-Bogart G, Webster H, Davis M, Johnson RC, et al. Progression of lung disease in preschool patients with cystic fibrosis. Am J Respir Crit Care Med 2017;195: 1216-1225.
37. 1 in cystic fibrosis patients treated with ivacaftor. J Cyst Fibros 2017;16:41-44.
38. Clancy JP, Rowe SM, Accurso FJ, Aitken ML, Amin RS, Ashlock MA, et al. Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation. Thorax 2012;67:12-18.
39. Kälin N, Claass A, Sommer M, Puchelle E, Tümmler B. DF508 CFTR protein expression in tissues from patients with cystic fibrosis. J Clin Invest 1999;103:1379-1389.
40. Kreda SM, Mall M, Mengos A, Rochelle L, Yankaskas J, Riordan JR, et al. Characterization of wild-type and DF508 cystic fibrosis transmembrane regulator in human respiratory epithelia. Mol Biol Cell 2005;16:2154-2167.
41. van Barneveld A, Stanke F, Tamm S, Siebert B, Brandes G, Derichs N, et al. Functional analysis of F508del CFTR in native human colon. Biochim Biophys Acta 2010;1802:1062-1069.
42. Collaco JM, Blackman SM, Raraigh KS, Corvol H, Rommens JM, Pace RG, et al. Sources of variation in sweat chloride measurements in cystic fibrosis. Am J Respir Crit Care Med 2016;194:1375-1382.
43. Rowe SM, Heltshe SL, Gonska T, Donaldson SH, Borowitz D, Gelfond D, et al.; GOAL Investigators of the Cystic Fibrosis Foundation Therapeutics Development Network. Clinical mechanism of the cystic fibrosis transmembrane conductance regulator potentiator ivacaftor in G551D-mediated cystic fibrosis. Am J Respir Crit Care Med 2014;190:175-184.
44. Hisert KB, Heltshe SL, Pope C, Jorth P, Wu X, Edwards RM, et al. Restoring cystic fibrosis transmembrane conductance regulator function reduces airway bacteria and inflammation in people with cystic fibrosis and chronic lung infections. Am J Respir Crit Care Med 2017;195:1617-1628.
45. Ronan NJ, Einarsson GG, Twomey M, Mooney D, Mullane D, NiChroinin M, et al. CORK study in cystic fibrosis: sustained improvements in ultra-low-dose chest CT scores after CFTR modulation with ivacaftor. Chest 2018;153:395-403.
46. Bronsveld I, Mekus F, Bijman J, Ballmann M, de Jonge HR, Laabs U, et al. Chloride conductance and genetic background modulate the cystic fibrosis phenotype of DF508 homozygous twins and siblings. J Clin Invest 2001;108:1705-1715.
47. Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Dřevínek P, et al.; VX08-770-102 Study Group. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 2011;365: 1663-1672.
48. Rowe SM, Daines C, Ringshausen FC, Kerem E, Wilson J, Tullis E, et al. Tezacaftor-ivacaftor in residual-function heterozygotes with cystic fibrosis. N Engl J Med 2017;377:2024-2035.