Efficacy and safety of an anti-IL-13 mAb in patients with severe asthma: A randomized trial

Journal of Allergy and Clinical Immunology

Volumn 133, Issue 4, 2014, Pages

  De Boever, Erika H ^a   Ashman, Claire ^b   Cahn, Anthony P ^b   Locantore, Nicholas W ^a   Overend, Phil ^b   Pouliquen, Isabelle J ^a   Serone, Adrian P ^c   Wright, Tracey J ^b   Jenkins, Mair M ^b   Panesar, Inderpal S ^d   Thiagarajah, Sivayogan S ^e   Wenzel, Sally E ^f  

^a GLAXOSMITHKLINE   (United States)

^b GLAXOSMITHKLINE   (United Kingdom)

^c GENENTECH INC   (United States)

^d ISP Pharma   (United Kingdom)

^e Janssen   (United Kingdom)

^f UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

Author keywords

efficacy; IL 13; IL13R 1; IL13R 2; pharmacodynamics; pharmacokinetics; safety

Indexed keywords

ANTIASTHMATIC AGENT; FLUTICASONE PROPIONATE; GSK 679586; GSK679586; IMMUNOGLOBULIN E; INTERLEUKIN 13 ANTIBODY; INTERLEUKIN 13 RECEPTOR ALPHA1; INTERLEUKIN 13 RECEPTOR ALPHA2; PLACEBO; UNCLASSIFIED DRUG;

ADULT; AGED; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; ASTHMA; BACKACHE; CONTROLLED STUDY; DIARRHEA; DISEASE EXACERBATION; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TOLERABILITY; EOSINOPHIL COUNT; FATIGUE; FEMALE; FORCED EXPIRATORY VOLUME; FORCED VITAL CAPACITY; HUMAN; HYPERTENSION; LETHARGY; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; PERIPHERAL EDEMA; PHARYNGITIS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SUPRAVENTRICULAR PREMATURE BEAT; TREATMENT OUTCOME; UPPER RESPIRATORY TRACT INFECTION; YOUNG ADULT;

EFFICACY; IL-13; IL13RΑ1; IL13RΑ2; PHARMACODYNAMICS; PHARMACOKINETICS; SAFETY;

ADULT; ANTI-ASTHMATIC AGENTS; ANTIBODIES, MONOCLONAL; ASTHMA; FEMALE; HUMANS; INTERLEUKIN-13; MALE; MIDDLE AGED; SEVERITY OF ILLNESS INDEX; TREATMENT OUTCOME;

EID: 84897379012     PISSN: 00916749     EISSN: 10976825     Source Type: Journal    
DOI: 10.1016/j.jaci.2014.01.002     Document Type: Article

References (44)

1. E.D. Bateman, H.A. Boushey, J. Bousquet, W.W. Busse, T.J.H. Clark, and R.A. Pauwels et al. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study Am J Respir Crit Care Med 170 2004 836 844
2. S. Wenzel Pathology of difficult asthma Paediatr Respir Rev 4 2003 306 311
3. S.D. Sullivan, L. Rasouliyan, P.A. Russo, T. Kamath, B.E. Chipps for the TENOR Study Group Extent, patterns, and burden of uncontrolled disease in severe or difficult-to-treat asthma Allergy 62 2007 126 133
4. N.S. Breekveldt-Postma, J.A. Erkens, R. Aalbers, M.J.T. van de Ven, J.J. Lammers, and R.M.C. Herings Extent of uncontrolled disease and associated medical costs in severe asthma - a PHARMO study Curr Med Res Opin 24 2008 975 983
5. R.H. Green, C.E. Brightling, and P. Bradding The reclassification of asthma based on subphenotypes Curr Opin Allergy Clin Immunol 7 2007 43 50
6. P. Haldar, I.D. Pavord, D.E. Shaw, M.A. Berry, M. Thomas, and C.E. Brightling Cluster analysis and clinical asthma phenotypes Am J Respir Crit Care Med 178 2008 218 224
7. P.B. Bradding, and R.H. Green Subclinical phenotypes of asthma Curr Opin Allergy Clin Immunol 10 2010 54 59
8. P.G. Woodruff, B. Modrek, D.F. Choy, G. Jia, A.R. Abbas, and A. Ellwanger et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma Am J Respir Crit Care Med 180 2009 388 395
9. M. Wills-Karp, J. Luyimbazi, X. Xu, B. Schofield, T.Y. Neben, and C.L. Karp et al. Interleukin-13: Central mediator in allergic asthma Science 282 1998 2258 2261
10. M. Wills-Karp Interleukin-13 in asthma pathogenesis Immunol Rev 202 2004 175 190
11. Z. Zhu, R.J. Homer, Z. Wang, Q. Chen, G.P. Geba, and J. Wang Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production J Clin Invest 103 1999 779 788
12. G. Yang, A. Volk, T. Petley, E. Emmell, J. Giles-Komar, and X. Shang et al. Anti-IL-13 monoclonal antibody inhibits airway hyperresponsiveness, inflammation and airway remodeling Cytokine 28 2004 224 232
13. P.C. Fulkerson, C.A. Fischetti, L.M. Hassman, N.M. Nikolaidis, and M.E. Rothenberg Persistent effects induced by IL-13 in the lung Am J Respir Cell Mol Biol 35 2006 337 346
14. S.K. Saha, M.A. Berry, D. Parker, S. Siddiqui, A. Morgan, and R. May et al. Increased sputum and bronchial biopsy IL-13 expression in severe asthma J Allergy Clin Immunol 121 2008 685 691
15. R.G. Townley, P.R. Gendapodi, N. Qutna, J. Evans, F.A. Romero, and P. Abel Effect of interleukin 13 on bronchial hyperresponsiveness and the bronchoprotective effect of beta-adrenergic bronchodilators and corticosteroids Ann Allergy Asthma Immunol 102 2009 190 197
16. M. Kraft, C. Lewis, D. Pham, and H.W. Chu IL-4, IL-13, and dexamethasone augment fibroblast proliferation in asthma J Allergy Clin Immunol 107 2001 602 606
17. J.D. Spahn, S.J. Szefler, W. Surs, D.E. Doherty, S.R. Nimmagadda, and D.Y. Leung A novel action of IL-13: induction of diminished monocyte glucocorticoid receptor-binding affinity J Immunol 157 1996 2654 2659
18. S. Allahverdian, N. Harada, G.K. Singhera, D.A. Knight, and D.R. Dorscheid Secretion of IL-13 by airway epithelial cells enhances epithelial repair via HB-EGF Am J Respir Cell Mol Biol 38 2008 153 160
19. V. Ruíz-González, J.C. Cancino-Diaz, S. Rodríguez-Martínez, and M.E. Cancino-Diaz Keratinocytes treated with peptidoglycan from Staphylococcus aureus produce vascular endothelial growth factor, and its expression is amplified by the subsequent production of interleukin-13 Int J Dermatol 48 2009 846 854
20. S. Fichtner-Feigl, W. Strober, K. Kawakami, R.K. Puri, and A. Kitani IL-13 signaling through the IL-13α2 receptor is involved in induction of TGF-β1 production and fibrosis Nat Med 12 2006 99 106
21. W. Strober, A. Kitani, S. Fichtner-Feigl, and I.J. Fuss The signaling function of the IL13Rα2 receptor in the development of gastrointestinal fibrosis and cancer surveillance Curr Mol Med 9 2009 740 750
22. S.L. LaPorte, Z.S. Juo, J. Vaclavikova, L.A. Colf, X. Qi, and N.M. Heller et al. Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system Cell 132 2008 259 272
23. G.K. Hershey IL-13 receptors and signaling pathways: an evolving web J Allergy Clin Immunol 111 2003 677 690
24. P.J. Lupardus, M.E. Birnbaum, and K.C. Garcia Molecular basis for shared cytokine recognition revealed in the structure of an unusually high affinity complex between IL-13 and IL-13 Rα2 Structure 18 2010 332 342
25. P. Hodsman, C. Ashman, T. Cahn, E. De Boever, N. Locantore, and A. Serone et al. I13105054: a dose-escalating study of the safety and pharmacokinetics of GSK679586 in healthy volunteers and mild asthmatics Br J Clin Pharmacol 75 2013 118 128
26. E.F. Juniper, P.M. O'Byrne, G.H. Guyatt, P.J. Ferrie, and D.R. King Development and validation of a questionnaire to measure asthma control Eur Respir J 14 1999 902 907
27. E.F. Juniper, P.M. O'Bryne, P.J. Ferrie, D.R. King, and J.N. Roberts Measuring asthma control. Clinic questionnaire or daily diary Am J Respir Crit Care Med 162 2000 1330 1334
28. N.L. Dirks, and B. Meibohm Population pharmacokinetics of therapeutic monoclonal antibodies Clin Pharmacokinet 49 2010 633 659
29. R.C. Littell, G.A. Milliken, W.W. Stroup, R.D. Wolfinger, and O. Schabenberger SAS for mixed models 2nd ed. 2006 SAS Institute Cary (NC)
30. J. Corren, R.F. Lemanske, N.A. Hanania, P.E. Korenblat, M.V. Parsey, and J.R. Arron et al. Lebrikizumab treatment in adults with asthma N Engl J Med 365 2011 1088 1098
31. E. Piper, C. Brightling, R. Niven, C. Oh, R. Faggioni, and K. Poon et al. A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma Eur Respir J 41 2013 330 338
32. J. Corren, W. Busse, E.O. Meltzer, L. Mansfield, G. Bensch, and J. Fahrenholz et al. A randomized, controlled, Phase 2 study of AMG 317, an IL-4Rα antagonist, in patients with asthma Am J Respir Crit Care Med 181 2010 788 796
33. Wenzel S, Ind PW, Otulana BA, Bleecker ER, Kuna P, Yen YP. Inhaled pitrakinra, an IL-4/IL-13 antagonist, reduced exacerbations in patients with eosinophilic asthma [abstract]. Abstract #P3980. Available at: www.ersnet.org.
34. S.E. Wenzel, L. Ford, D. Pearlman, S. Spector, L. Sher, and F. Skobieranda et al. Dupilumab in persistent asthma with elevated eosinophil levels N Engl J Med 368 2013 2455 2466
35. A. Jatakanon, S. Karitonov, S. Lim, and P.J. Barnes Effect of differing doses of inhaled budesonide on markers of airway inflammation in patients with mild asthma Thorax 54 1999 108 114
36. D.K. Shah, and A.M. Betts Antibody biodistribution coefficients. Inferring tissue concentrations of monoclonal antibodies based on the plasma concentrations in several preclinical species and human mAbs 5 2013 297 305
37. M. Tabrizi, G.G. Bornstein, and H. Suria Biodistribution mechanisms of therapeutic monoclonal antibodies in health and disease AAPS J 12 2010 33 43
38. I. Pavord, S. Kern, P. Howarth, E.R. Bleecker, R. Buhl, and O.N. Keene et al. Mepolizumab for Severe Eosinophilic Asthma (DREAM): a multicentre, double-blind, placebo-controlled trial Lancet 380 2012 651 659
39. M.T. Kasaian, D. Raible, K. Marquette, T.A. Cook, S. Zhou, and X.Y. Tan et al. IL-13 antibodies influence IL-13 clearance in humans by modulating scavenger activity of IL-13Rα2 J Immunol 187 2011 561 569
40. D.C. Newcomb, M.G. Boswell, W. Zhou, M.M. Huckabee, K. Goleniewska, and C.M. Sevin et al. Human Th17 cells express a functional IL-13 receptor and IL-13 attenuates IL17A production J Allergy Clin Immunol 127 2011 1006 1013
41. D.C. Newcomb, and R.S. Peebles Th17-mediated inflammation in asthma Curr Opin Immunol 25 2013 755 760
42. M.R. Miller, J. Hankinson, J. Odencrantz, V. Brusasco, F. Burgos, and R. Casaburi et al. Standardization of spirometry Eur Respir J 26 2005 319 338
43. K.K.G. Lan, and J. Wittes The B-value: a tool for monitoring data Biometrics 44 1988 579 585
44. R.C. Littell, G.A. Milliken, W.W. Stroup, R.D. Wolfinger, and O. Schabenberger SAS for mixed models 2nd ed. 2006 SAS Institute Cary (NC)