Development of new therapies for severe asthma

Allergy, Asthma and Immunology Research

Volumn 9, Issue 1, 2017, Pages 3-14

  Fajt, Merritt L ^a   Wenzel, Sally E ^a  

^a UNIVERSITY OF PITTSBURGH MEDICAL CENTER   (United States)

Author keywords

Asthma phenotype; Biologic medications; Severe asthma; Type 2 inflammation

Indexed keywords

CORTICOSTEROID; IMMUNOGLOBULIN E; IMMUNOSUPPRESSIVE AGENT; INTERLEUKIN 13; INTERLEUKIN 4; INTERLEUKIN 5; MUSCARINIC AGENT; PROSTAGLANDIN D2;

ASTHMA; BIOLOGICAL THERAPY; BRONCHIAL THERMOPLASTY; DRUG EFFICACY; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; LUNG FUNCTION; PHENOTYPE; REVIEW; TREATMENT RESPONSE;

EID: 85007552176     PISSN: 20927355     EISSN: 20927363     Source Type: Journal    
DOI: 10.4168/aair.2017.9.1.3     Document Type: Review

References (84)

1. National Heart, Lung, and Blood Institute (US). Guidelines for the diagnosis and management of asthma: expert panel report 3 [Internet]. Bethesda (MD): U.S. Department of Health and Human Services; 2007 [cited 2015 Nov 11]. Available from: http://www.nhlbi. nih.gov/guidelines/asthma/asthgdln.pdf.
2. Chung KF, Wenzel S; European Respiratory Society/American Thoracic Society Severe Asthma International Guidelines Task Force. From the authors: International European Respiratory Society/American Thoracic Society guidelines on severe asthma. Eur Respir J 2014;44:1378-9.
3. Wenzel SE, Busse WW; National Heart, Lung, and Blood Institute's Severe Asthma Research Program. Severe asthma: lessons from the Severe Asthma Research Program. J Allergy Clin Immunol 2007;119: 14-21.
4. Brown HM. Treatment of chronic asthma with prednisolone; significance of eosinophils in the sputum. Lancet 1958;2:1245-7.
5. Pavord ID, Brightling CE, Woltmann G, Wardlaw AJ. Non-eosinophilic corticosteroid unresponsive asthma. Lancet 1999;353:2213-4.
6. Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009;360:973-84.
7. Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 2009;360:985-93.
8. Woodruff PG, Boushey HA, Dolganov GM, Barker CS, Yang YH, Donnelly S, et al. Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids. Proc Natl Acad Sci U S A 2007;104:15858-63.
9. Woodruff PG, Modrek B, Choy DF, Jia G, Abbas AR, Ellwanger A, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med 2009;180:388-95.
10. Jia G, Erickson RW, Choy DF, Mosesova S, Wu LC, Solberg OD, et al. Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients. J Allergy Clin Immunol 2012;130:647-654.e10.
11. Corren J, Lemanske RF Jr, Hanania NA, Korenblat PE, Parsey MV, Arron JR, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med 2011;365:1088-98.
12. Chibana K, Trudeau JB, Mustovich AT, Hu H, Zhao J, Balzar S, et al. IL-13 induced increases in nitrite levels are primarily driven by increases in inducible nitric oxide synthase as compared with effects on arginases in human primary bronchial epithelial cells. Clin Exp Allergy 2008;38:936-46.
13. Dweik RA, Sorkness RL, Wenzel S, Hammel J, Curran-Everett D, Comhair SA, et al. Use of exhaled nitric oxide measurement to identify a reactive, at-risk phenotype among patients with asthma. Am J Respir Crit Care Med 2010;181:1033-41.
14. Wenzel S, Wilbraham D, Fuller R, Getz EB, Longphre M. Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. Lancet 2007;370:1422-31.
15. Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med 2013;368:2455-66.
16. Kerstjens HA, Disse B, Schröder-Babo W, Bantje TA, Gahlemann M, Sigmund R, et al. Tiotropium improves lung function in patients with severe uncontrolled asthma: a randomized controlled trial. J Allergy Clin Immunol 2011;128:308-14.
17. Kerstjens HA, Engel M, Dahl R, Paggiaro P, Beck E, Vandewalker M, et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med 2012;367:1198-207.
18. Boehringer Ingelheim GmbH (DE). Asthma: U.S. FDA approves new indication for SPIRIVA® Respimat® [Internet]. [cited 2015 Nov 11] Avaliable from: http://us.boehringer-ingelheim.com/news_ events/press_releases/press_release_archive/2015/fda-approvesboehringer-ingelheims-spiriva-respimat-maintenance-treatmentasthma-adults-adolescents.html.
19. Global Initiative for Asthma. Global strategy for asthma management and prevention [Internet]. Global Initiative for Asthma; 2015 [updated 2015 Apr; acessed 2015 Oct 17]. Available from: http://www.ginasthma.org/local/uploads/files/GINA_Report_2015.pdf.
20. Evans DJ, Kew KM, Anderson DE, Boyter AC. Long-acting muscarinic antagonists (LAMA) added to inhaled corticosteroids (ICS) versus higher dose ICS for adults with asthma. Cochrane Database Syst Rev 2015;7:CD011437.
21. Anderson DE, Kew KM, Boyter AC. Long-acting muscarinic antagonists (LAMA) added to inhaled corticosteroids (ICS) versus the same dose of ICS alone for adults with asthma. Cochrane Database Syst Rev 2015;8:CD011397.
22. Castro M, Rubin AS, Laviolette M, Fiterman J, De Andrade Lima M, Shah PL, et al. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J Respir Crit Care Med 2010;181:116-24.
23. Castro M, Rubin A, Laviolette M, Hanania NA, Armstrong B, Cox G. Persistence of effectiveness of bronchial thermoplasty in patients with severe asthma. Ann Allergy Asthma Immunol 2011;107:65-70.
24. Wechsler ME, Laviolette M, Rubin AS, Fiterman J, Lapa e Silva JR, Shah PL, et al. Bronchial thermoplasty: long-term safety and effectiveness in patients with severe persistent asthma. J Allergy Clin Immunol 2013;132:1295-302.
25. Pretolani M, Dombret MC, Thabut G, Knap D, Hamidi F, Debray MP, et al. Reduction of airway smooth muscle mass by bronchial thermoplasty in patients with severe asthma. Am J Respir Crit Care Med 2014;190:1452-4.
26. Chakir J, Haj-Salem I, Gras D, Joubert P, Beaudoin EL, Biardel S, et al. Effects of bronchial thermoplasty on airway smooth muscle and collagen deposition in asthma. Ann Am Thorac Soc 2015;12:1612-8.
27. Denner DR, Doeing DC, Hogarth DK, Dugan K, Naureckas ET, White SR. Airway inflammation after bronchial thermoplasty for severe asthma. Ann Am Thorac Soc 2015;12:1302-9.
28. Torrego A, Solà I, Munoz AM, Roqué I Figuls M, Yepes-Nuñez JJ, Alonso-Coello P, et al. Bronchial thermoplasty for moderate or severe persistent asthma in adults. Cochrane Database Syst Rev 2014; 3:CD009910.
29. Busse W, Corren J, Lanier BQ, McAlary M, Fowler-Taylor A, Cioppa GD, et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol 2001;108:184-90.
30. Solèr M, Matz J, Townley R, Buhl R, O'Brien J, Fox H, et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J 2001;18:254-61.
31. Holgate ST, Chuchalin AG, Hébert J, Lötvall J, Persson GB, Chung KF, et al. Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Clin Exp Allergy 2004;34:632-8.
32. Hanania NA, Alpan O, Hamilos DL, Condemi JJ, Reyes-Rivera I, Zhu J, et al. Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial. Ann Intern Med 2011;154:573-82.
33. Hanania NA, Wenzel S, Rosén K, Hsieh HJ, Mosesova S, Choy DF, et al. Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in the EXTRA study. Am J Respir Crit Care Med 2013;187:804-11.
34. Walker S, Monteil M, Phelan K, Lasserson TJ, Walters EH. Anti-IgE for chronic asthma in adults and children. Cochrane Database Syst Rev 2006;2:CD003559.
35. Normansell R, Walker S, Milan SJ, Walters EH, Nair P. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev 2014;1:CD003559.
36. Miranda C, Busacker A, Balzar S, Trudeau J, Wenzel SE. Distinguishing severe asthma phenotypes: role of age at onset and eosinophilic inflammation. J Allergy Clin Immunol 2004;113:101-8.
37. Haldar P, Pavord ID, Shaw DE, Berry MA, Thomas M, Brightling CE, et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 2008;178:218-24.
38. Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X, et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med 2010; 181:315-23.
39. Amelink M, de Groot JC, de Nijs SB, Lutter R, Zwinderman AH, Sterk PJ, et al. Severe adult-onset asthma: a distinct phenotype. J Allergy Clin Immunol 2013;132:336-41.
40. Proceedings of the ATS workshop on refractory asthma: current un derstanding, recommendations, and unanswered questions. American Thoracic Society. Am J Respir Crit Care Med 2000;162:2341-51.
41. Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012;380: 651-9.
42. Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 2014;371:1198-207.
43. Prazma CM, Wenzel S, Barnes N, Douglass JA, Hartley BF, Ortega H. Characterisation of an OCS-dependent severe asthma population treated with mepolizumab. Thorax 2014;69:1141-2.
44. Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 2014;371:1189-97.
45. Castro M, Mathur S, Hargreave F, Boulet LP, Xie F, Young J, et al. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study. Am J Respir Crit Care Med 2011;184: 1125-32.
46. Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med 2015;3:355-66.
47. Kolbeck R, Kozhich A, Koike M, Peng L, Andersson CK, Damschroder MM, et al. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol 2010;125:1344-1353.e2.
48. Castro M, Wenzel SE, Bleecker ER, Pizzichini E, Kuna P, Busse WW, et al. Benralizumab, an anti-interleukin 5 receptor a monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study. Lancet Respir Med 2014;2:879-90.
49. Nowak RM, Parker JM, Silverman RA, Rowe BH, Smithline H, Khan F, et al. A randomized trial of benralizumab, an antiinterleukin 5 receptor a monoclonal antibody, after acute asthma. Am J Emerg Med 2015;33:14-20.
50. Katz LE, Gleich GJ, Hartley BF, Yancey SW, Ortega HG. Blood eosinophil count is a useful biomarker to identify patients with severe eosinophilic asthma. Ann Am Thorac Soc 2014;11:531-6.
51. Nucala (mepolizumab): highlights of prescribing information [Internet]. Philadelphia (PA): GlaxoSmithKline LLC; 2015 Nov [cited 2015 Dec 1]. Available from: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Nucala/pdf/NUCALA-PI-PIL.PDF.
52. Corren J, Busse W, Meltzer EO, Mansfield L, Bensch G, Fahrenholz J, et al. A randomized, controlled, phase 2 study of AMG 317, an IL-4Ralpha antagonist, in patients with asthma. Am J Respir Crit Care Med 2010;181:788-96.
53. Piper E, Brightling C, Niven R, Oh C, Faggioni R, Poon K, et al. A phase II placebo-controlled study of tralokinumab in moderate-tosevere asthma. Eur Respir J 2013;41:330-8.
54. Brightling CE, Chanez P, Leigh R, O'Byrne PM, Korn S, She D, et al. Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Respir Med 2015;3:692-701.
55. Hanania NA, Noonan M, Corren J, Korenblat P, Zheng Y, Fischer SK, et al. Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies. Thorax 2015;70: 748-56.
56. De Boever EH, Ashman C, Cahn AP, Locantore NW, Overend P, Pouliquen IJ, et al. Efficacy and safety of an anti-IL-13 mAb in patients with severe asthma: a randomized trial. J Allergy Clin Immunol 2014;133:989-96.
57. Wenzel SE, Wang L, Pirozzi G, Sutherland ER, Graham N, Evans RR, et al. Dupilumab improves lung function and reduces severe exacerbations in uncontrolled asthmatics with baseline eosinophil levels above and below 300 cells/μL. Am J Respir Crit Care Med 2015;191:A6362.
58. Balzar S, Fajt ML, Comhair SA, Erzurum SC, Bleecker E, Busse WW, et al. Mast cell phenotype, location, and activation in severe asthma. Data from the Severe Asthma Research Program. Am J Respir Crit Care Med 2011;183:299-309.
59. Fajt ML, Gelhaus SL, Freeman B, Uvalle CE, Trudeau JB, Holguin F, et al. Prostaglandin D2 pathway upregulation: relation to asthma severity, control, and TH2 inflammation. J Allergy Clin Immunol 2013;131:1504-12.
60. Pettipher R, Hansel TT, Armer R. Antagonism of the prostaglandin D2 receptors DP1 and CRTH2 as an approach to treat allergic diseases. Nat Rev Drug Discov 2007;6:313-25.
61. Licona-Limón P, Kim LK, Palm NW, Flavell RA. TH2, allergy and group 2 innate lymphoid cells. Nat Immunol 2013;14:536-42.
62. Barnes N, Pavord I, Chuchalin A, Bell J, Hunter M, Lewis T, et al. A randomized, double-blind, placebo-controlled study of the CRTH2 antagonist OC000459 in moderate persistent asthma. Clin Exp Allergy 2012;42:38-48.
63. Pettipher R, Hunter MG, Perkins CM, Collins LP, Lewis T, Baillet M, et al. Heightened response of eosinophilic asthmatic patients to the CRTH2 antagonist OC000459. Allergy 2014;69:1223-32.
64. Hall IP, Fowler AV, Gupta A, Tetzlaff K, Nivens MC, Sarno M, et al. Efficacy of BI 671800, an oral CRTH2 antagonist, in poorly controlled asthma as sole controller and in the presence of inhaled corticosteroid treatment. Pulm Pharmacol Ther 2015;32:37-44.
65. Berair R, Singapuri A, Hartley R, Laurencin M, Bacher G, Holzhauer B, et al. Effect of Qaw039, an oral prostaglandin D2 receptor (DP2/CrTh2) antagonist, upon sputum and bronchial eosinophilic inflammation and clinical outcomes in treatment-resistant asthma: a phase 2a randomized placebo-controlled trial. Am J Respir Crit Care Med 2015;191:A6361.
66. Berry MA, Hargadon B, Shelley M, Parker D, Shaw DE, Green RH, et al. Evidence of a role of tumor necrosis factor alpha in refractory asthma. N Engl J Med 2006;354:697-708.
67. Morjaria JB, Chauhan AJ, Babu KS, Polosa R, Davies DE, Holgate ST. The role of a soluble TNFalpha receptor fusion protein (etanercept) in corticosteroid refractory asthma: a double blind, randomised, placebo controlled trial. Thorax 2008;63:584-91.
68. Wenzel SE, Barnes PJ, Bleecker ER, Bousquet J, Busse W, Dahlén SE, et al. A randomized, double-blind, placebo-controlled study of tumor necrosis factor-alpha blockade in severe persistent asthma. Am J Respir Crit Care Med 2009;179:549-58.
69. Pelletier M, Maggi L, Micheletti A, Lazzeri E, Tamassia N, Costantini C, et al. Evidence for a cross-talk between human neutrophils and Th17 cells. Blood 2010;115:335-43.
70. Busse WW, Holgate S, Kerwin E, Chon Y, Feng J, Lin J, et al. Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma. Am J Respir Crit Care Med 2013;188:1294-302.
71. Chung KF. Targeting the interleukin pathway in the treatment of asthma. Lancet 2015;386:1086-96.
72. Wenzel SE, Szefler SJ, Leung DY, Sloan SI, Rex MD, Martin RJ. Bronchoscopic evaluation of severe asthma. Persistent inflammation associated with high dose glucocorticoids. Am J Respir Crit Care Med 1997;156:737-43.
73. Jatakanon A, Uasuf C, Maziak W, Lim S, Chung KF, Barnes PJ. Neutrophilic inflammation in severe persistent asthma. Am J Respir Crit Care Med 1999;160:1532-9.
74. Hastie AT, Moore WC, Meyers DA, Vestal PL, Li H, Peters SP, et al. Analyses of asthma severity phenotypes and inflammatory proteins in subjects stratified by sputum granulocytes. J Allergy Clin Immunol 2010;125:1028-1036.e13.
75. Moore WC, Hastie AT, Li X, Li H, Busse WW, Jarjour NN, et al. Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis. J Allergy Clin Immunol 2014; 133:1557-1563.e5.
76. Nair P, Gaga M, Zervas E, Alagha K, Hargreave FE, O'Byrne PM, et al. Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils: a randomized, placebo-controlled clinical trial. Clin Exp Allergy 2012;42:1097-103.
77. Uzun S, Djamin RS, Kluytmans JA, Mulder PG, van't Veer NE, Ermens AA, et al. Azithromycin maintenance treatment in patients with frequent exacerbations of chronic obstructive pulmonary disease (COLUMBUS): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med 2014;2:361-8.
78. Altenburg J, de Graaff CS, Stienstra Y, Sloos JH, van Haren EH, Koppers RJ, et al. Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled trial. JAMA 2013; 309:1251-9.
79. Serisier DJ, Martin ML, McGuckin MA, Lourie R, Chen AC, Brain B, et al. Effect of long-term, low-dose erythromycin on pulmonary exacerbations among patients with non-cystic fibrosis bronchiectasis: the BLESS randomized controlled trial. JAMA 2013;309:1260-7.
80. Brusselle GG, Vanderstichele C, Jordens P, Deman R, Slabbynck H, Ringoet V, et al. Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial. Thorax 2013;68:322-9.
81. Mullarkey MF, Lammert JK, Blumenstein BA. Long-term methotrexate treatment in corticosteroid-dependent asthma. Ann Intern Med 1990;112:577-81.
82. Erzurum SC, Leff JA, Cochran JE, Ackerson LM, Szefler SJ, Martin RJ, et al. Lack of benefit of methotrexate in severe, steroid-dependent asthma. A double-blind, placebo-controlled study. Ann Intern Med 1991;114:353-60.
83. Davies H, Olson L, Gibson P. Methotrexate as a steroid sparing agent for asthma in adults. Cochrane Database Syst Rev 2000: CD000391.
84. Wenzel SE, Vitari CA, Shende M, Strollo DC, Larkin A, Yousem SA. Asthmatic granulomatosis: a novel disease with asthmatic and granulomatous features. Am J Respir Crit Care Med 2012;186:501-7.