Emerging drugs for asthma

Expert Opinion on Emerging Drugs

Volumn 17, Issue 2, 2012, Pages 219-237

  Quirce, Santiago ^a   Bobolea, Irina ^b   Barranco, Pilar ^b  

^a HOSPITAL UNIVERSITARIO LA PAZ   (Spain)

^b HOSPITAL UNIVERSITARIO LA PAZ IDIPAZ   (Spain)

Author keywords

Biological treatments; Combination therapy; Monoclonal antibodies; Novel bronchodilators

Indexed keywords

ABEDITEROL; BECLOMETASONE; BENRALIZUMAB; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; BUDESONIDE; CARMOTEROL; CHEMOATTRACTANT; CICLESONIDE; CILOMILAST; FLUTICASONE FUROATE; FLUTICASONE PROPIONATE PLUS SALMETEROL; FORMOTEROL; INDACATEROL; LEUKOTRIENE RECEPTOR BLOCKING AGENT; MEPOLIZUMAB; MILVETEROL; MOMETASONE FUROATE; MONTELUKAST; OC 000459; OLODATEROL; OMALIZUMAB; PF 610355; PITRAKINRA; PLACEBO; QAX 576; RESLIZUMAB; ROFLUMILAST; SALBUTAMOL; SALMETEROL; SK 159797; TIOTROPIUM BROMIDE; TRALOKINUMAB; UNCLASSIFIED DRUG; VILANTEROL; ZAFIRLUKAST; ZILEUTON;

ADJUVANT THERAPY; ALLERGIC ASTHMA; ALLERGIC RHINITIS; ASTHMA; BRONCHITIS; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL TRIAL (TOPIC); DIABETES MELLITUS; DOUBLE BLIND PROCEDURE; DRUG SAFETY; DRUG SUBSTITUTION; DRUG TOLERABILITY; DRUG WITHDRAWAL; EVENING DOSAGE; HEADACHE; HUMAN; LIVER CIRRHOSIS; NAUSEA; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); RESPIRATORY TRACT INFECTION; REVIEW; SCHIZOPHRENIA; SINGLE DRUG DOSE; TH2 CELL;

ANIMALS; ANTI-ASTHMATIC AGENTS; ASTHMA; CLINICAL TRIALS AS TOPIC; DRUG EVALUATION, PRECLINICAL; HUMANS; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 84861595358     PISSN: 14728214     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728214.2012.683410     Document Type: Review

References (124)

1. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention: NHLBI/WHO workshop report. Bethesda: National Institutes of Health, National Heart, Lung and Blood Institute. Updated 2010. Available from: http://www. ginasthma.com
2. Masoli M, Fabian D, Holt S, Beasley R. Global Initiative for Asthma (GINA) program the global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 2004;59:469-78 (Pubitemid 38580764)
3. Bahadori K, Doyle-Waters MM, Marra C, et al. Economic burden of asthma: a systematic review. BMC Pulm Med 2009;9:24
4. Lotvall J, Akdis CA, Bacharier LB, et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol 2011;127:355-60
5. Bel EH, Sousa A, Fleming L, et al. Unbiased Biomarkers for the Prediction of Respiratory Disease Outcome (U-BIOPRED) Consortium, Consensus Generation. Diagnosis and definition of severe refractory asthma: an international consensus statement from the Innovative Medicine Initiative (IMI). Thorax 2011;66:910-17
6. Pavord ID, Wardlaw AJ. The A to E of airway disease. Clin Exp Allergy 2010;40:62-7
7. Reddel HK, Taylor DR, Bateman ED, et al. An official American ThoracicSociety/European Respiratory Society statement: asthma control and exacerbations. Standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med 2009;180:59-99
8. Bateman ED, Reddel HK, Eriksson G, et al. Overall asthma control: the relationship between current control and future risk. J Allergy Clin Immunol 2010;125:600-8
9. Bateman ED, Boushey HA, Bousquet J, et al. GOAL Investigators Group. Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study. Am J Respir Crit Care Med 2004;170:836-44 (Pubitemid 39346477)
10. Chapman KR, Boulet LP, Rea RM, Franssen E. Suboptimal asthma control: prevalence, detection and consequences in general practice. Eur Respir J 2008;31:320-5
11. Partridge MR, van der Molen T, Myrseth SE, Busse WW. Attitudes and actions of asthma patients on regular maintenance therapy: the INSPIRE study. BMC Pulm Med 2006;6:13
12. The ENFUMOSA study group. The ENFUMOSA cross-sectional European multicentre study of the clinical phenotype of chronic severe asthma. Eur Respir J 2003;22:470-7
13. Green RH, Brightling CE, Woltmann G, et al. Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids. Thorax 2002;57:875-9 (Pubitemid 35178612)
14. Berry M, Morgan A, Shaw DE, et al. Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax 2007;62:1043-9 (Pubitemid 350206195)
15. Sastre B, Fernandez-Nieto M, Molla R, et al. Increased prostaglandin E2 levels in the airway of patients with eosinophilic bronchitis. Allergy 2008;63:58-66 (Pubitemid 350198231)
16. Dahlen SE. Treatment of asthma with antileukotrienes: first line or last resort therapy? Eur J Pharmacol 2006;533:40-56
17. Price D, Musgrave SD, Shepstone L, et al. Leukotriene antagonists as first-line or add-on asthma-controller therapy. N Engl J Med 2011;364:1695-707
18. Busse WW, Morgan WJ, Gergen PJ, et al. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med 2011;364:1005-15
19. Kuhl K, Hanania NA. Targeting IgE in asthma. Curr Opin Pulm Med 2012;18:1-5
20. Bousquet J, Bousquet PJ, Godard P, Daures JP. The public health implications of asthma. Bull World Health Organ 2005;83:548-54 (Pubitemid 41003331)
21. Godard P, Chanez P, Siraudin L, et al. Costs of asthma are correlated with severity: a 1-yr prospective study. Eur Respir J 2002;19:61-7 (Pubitemid 34105569)
22. Humbert M, Beasley R, Ayres J, et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy 2005;60:309-16 (Pubitemid 40293346)
23. Kazani S, Wechsler ME, Israel E. The role of pharmacogenomics in improving the management of asthma. J Allergy Clin Immunol 2010;125:295-302; quiz 303-4
24. Tarantini F, Baiardini I, Passalacqua G, et al. Asthma treatment: 'magic bullets which seek their own targets'. Allergy 2007;62:605-10 (Pubitemid 46763449)
25. Shannon J, Ernst P, Yamauchi Y, et al. Differences in airway cytokine profile in severe asthma compared to moderate asthma. Chest 2008;133:420-6 (Pubitemid 351272400)
26. Pease JE, Sabroe I. The role of interleukin-8 and its receptors in inflammatory lung disease: implications for therapy. Am J Respir Med 2002;1:19-25 (Pubitemid 37038920)
27. Nocker RE, Schoonbrood DF, van de Graaf EA, et al. Interleukin-8 in airway inflammation in patients with asthma and chronic obstructive pulmonary disease. Int Arch Allergy Immunol 1996;109:183-91 (Pubitemid 26029386)
28. Pepe C, Foley S, Shannon J, et al. Differences in airway remodeling between subjects with severe and moderate asthma. J Allergy Clin Immunol 2005;116:544-9 (Pubitemid 41267126)
29. Howarth P, Babu K, Arshad H, et al. Tumour necrosis factor (TNF alpha) as a novel therapeutic target in symptomatic corticosteroid dependent asthma. Thorax 2005;60:1012-18 (Pubitemid 41705469)
30. Anticevich SZ, Hughes JM, Black JL, Armour CL. Induction of human airway hyperresponsiveness by tumour necrosis factor-alpha. Eur J Pharmacol 1995;284:221-5
31. Woodruff PG, Modrek B, Choy DF, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med 2009;180:388-95
32. Erratum, Am J Respir Crit Care Med 2009; 180: 796
33. Simpson JL, Scott R, Boyle MJ, Gibson PG. Inflammatory subtypes in asthma: assessment and identification using induced sputum. Respirology 2006;11:54-61
34. Grunig G, Warnock M, Wakil AE, et al. Requirement for IL-13 independently of IL-4 in experimental asthma. Science 1998;282:2261-3 (Pubitemid 29004075)
35. Zhu Z, Homer RJ, Wang Z, et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest 1999;103:779-88 (Pubitemid 29152623)
36. Saha SK, Berry MA, Parker D, et al. Increased sputum and bronchial biopsy IL-13 expression in severe asthma. J Allergy Clin Immunol 2008;121:685-91 (Pubitemid 351323866)
37. Ingram JL, Huggins MJ, Church TD, et al. Airway fibroblasts in asthma manifest an invasive phenotype. Am J Respir Crit Care Med 2011;183:1625-32
38. Kaiko G, Horvat J, Beagley K, Hansbro P. Immunological decision-making: how does the immune system decide to mount a helper T-cell response? Immunology 2008;123:326-38 (Pubitemid 351171197)
39. Schleimer R, Sterbinsky S, Kaiser J, et al. IL-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium. Association with expression of VCAM-1. J Immunol 1992;148:1086-92
40. Buttner C, Skupin A, Reimann T, et al. Local production of interleukin-4 during radiation induced pneumonitis and pulmonary fibrosis in rats: macrophages as a prominent source of interleukin-4. Am J Respir Cell Mol Biol 1997;17:315-25 (Pubitemid 127500836)
41. Hart P, Bonder C, Balogh J, et al. Differential responses of human monocytes and macrophages to IL-4 and IL-13. J Leukoc Biol 1999;66:575-8 (Pubitemid 29489882)
42. Sorg R, Enczmann J, Sorg U, et al. Identification of an alternatively spliced transcript of human interleukin-4 lacking the sequence encoded by exon 2. Exp Hematol 1993;21:560-3 (Pubitemid 24212351)
43. Giembycz MA, Lindsay MA. Pharmacology of the eosinophil. Pharmacol Rev 1999;51:213-340
44. Kouro T, Takatsu K. IL-5-and eosinophil-mediated inflammation: from discovery to therapy. Int Immunol 2009;21:1303-9
45. Chowdhury BA, Dal Pan G. The FDA and safe use of long-acting beta-agonists in the treatment of asthma. N Engl J Med 2010;362:1169-71
46. Kazani S, Israel E. Long-acting beta-agonists and inhaled corticosteroids: is the whole greater than the sum of its parts? J Allergy Clin Immunol 2010;125:357-8
47. Park HW, Yang MS, Park CS, et al. Additive role of tiotropium in severe asthmatics and Arg16Gly in ADRB2 as a potential marker to predict response. Allergy 2009;64:778-83
48. Bateman ED, Kornmann O, Schmidt P, et al. Tiotropium is noninferior to salmeterol in maintaining improved lung function in 16-Arg/Arg patients with asthma. J Allergy Clin Immunol 2011;128:315-22
49. Peters SP, Kunselman SJ, Icitovic N, et al. Tiotropium bromide step-up therapy for adults with uncontrolled asthma. N Engl J Med 2010;363:1715-26
50. Kerstjens HA, Disse B, Schroder-Babo W, et al. Tiotropium improves lung function in patients with severe uncontrolled asthma: a randomized controlled trial. J Allergy Clin Immunol 2011;128:308-14
51. Campbell LM. Once daily inhaled corticosteroids in mild to moderate asthma: improving acceptance of treatment. Drugs 1999;58:25-33 (Pubitemid 30192630)
52. Cazzola M, Calzetta L, Matera MG. beta2-adrenoceptor agonists: current and future direction. Br J Pharmacol 2011;163:4-17
53. Beeh KM, Beier J. Indacaterol: a new once daily long-acting beta (2) adrenoceptor agonist. Core Evid 2010;4:37-41
54. Chowdhury BA, Seymour SM, Michele TM, et al. The risks and benefits of indacaterol-the FDA's review. N Engl J Med 2011;365:2247-9
55. Cazzola M, Segreti A, Matera MG. Novel bronchodilators in asthma. Curr Opin Pulm Med 2010;16:6-12
56. Kanniess F, Boulet LP, Pierzchala W, et al. Efficacy and safety of indacaterol, a new 24-hour beta2-agonist, in patients with asthma: a dose-ranging study. J Asthma 2008;45:887-92
57. LaForce C, Alexander M, Deckelmann R, et al. Indacaterol provides sustained 24 h bronchodilation on once-daily dosing in asthma: a 7-day dose-ranging study. Allergy 2008;63:103-11 (Pubitemid 350198242)
58. Kikkawa H, Kanno K, Ikezawa K. TA-2005, a novel, long-acting, and selective beta 2-adrenoceptor agonist: characterization of its in vivo bronchodilating action in guinea pigs and cats in comparison with other beta 2-agonists. Biol Pharm Bull 1994;17:1047-52 (Pubitemid 24276338)
59. Voss HP, Donnell D, Bast A. Atypical molecular pharmacology of a new long-acting beta 2-adrenoceptor agonist, TA 2005. Eur J Pharmacol 1992;227:403-9
60. Voss HP, Shukrula S, Wu TS, et al. A functional beta-2 adrenoceptor-mediated chronotropic response in isolated guinea pig heart tissue: selectivity of the potent beta-2 adrenoceptor agonist TA 2005. J Pharmacol Exp Ther 1994;271:386-9 (Pubitemid 24333153)
61. Summerhill S, Stroud T, Nagendra R, et al. A cell-based assay to assess the persistence of action of agonists acting at recombinant human beta-2 adrenoceptors. J Pharmacol Toxicol Methods 2008;58:189-97
62. Cazzola M, Matera MG, Lotvall J. Ultra long-acting beta2-agonists in development for asthma and chronic obstructive pulmonary disease. Expert Opin Investig Drugs 2005;14:775-83 (Pubitemid 41030946)
63. Matera MG, Cazzola M. Ultra-long-acting beta2-adrenoceptor agonists. An emerging therapeutic option for asthma and COPD? Drugs 2007;67:503-15 (Pubitemid 46440309)
64. Cazzola M, Matera MG. Emerging inhaled bronchodilators: an update. Eur Respir J 2009;34:757-69
65. O'Byrne PM, van der Linde J, Cockcroft DW, et al. Prolonged bronchoprotection against inhaled methacholine by inhaled BI 1744, a long-acting beta(2)-agonist, in patients with mild asthma. J Allergy Clin Immunol 2009;124:1217-21
66. Glossop PA, Lane CA, Price DA, et al. Inhalation by design: novel ultra-long-acting beta(2)-adrenoreceptor agonists for inhaled once-daily treatment of asthma and chronic obstructive pulmonary disease that utilize a sulfonamide agonist headgroup. J Med Chem 2010;53:6640-52
67. Woodcock A, Bleecker ER, Busse WW, et al. Fluticasone furoate: once-daily evening treatment versus twice-daily treatment in moderate asthma. Respir Res 2011;12:160
68. Maspero JF, Nolte H, Cherrez-Ojeda I; P04139 Study Group. Long-term safety of mometasone furoate/formoterol combination for treatment of patients with persistent asthma. J Asthma 2010;47:1106-15
69. Busse WW, Bleecker ER, Bateman ED, et al. Fluticasone furoate demonstrates efficacy in patients with asthma symptomatic on medium doses of inhaled corticosteroid therapy: an 8-week, randomised, placebo-controlled trial. Thorax 2012;67:35-41
70. Diamant Z, Sampson AP. Anti-inflammatory mechanisms of leukotriene modulators. Clin Exp Allergy 1999;29:1449-53 (Pubitemid 29519272)
71. Diamant Z, Mantzouranis E, Bjermer L. Expert review of montelukast in the treatment of asthma and beyond. Exp Rev Clin Immunol 2009;5:639-58
72. Minoguchi K, Kohno Y, Minoguchi H, et al. Reduction of eosinophilic inflammation in the airways of patients with asthma using montelukast. Chest 2002;121:732-8 (Pubitemid 34251435)
73. Suppli Ulrik C, Diamant Z. Add-on montelukast to inhaled corticosteroids protects against excessive airway narrowing. Clin Exp Allergy 2010;40:576-81
74. Price D, Musgrave SD, Shepstone L, et al. Leukotriene antagonists as first-line or add-on asthma-controller therapy. N Engl J Med 2011;364:1695-707
75. Hirai H, Tanaka K, Yoshie O, et al. Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J Exp Med 2001;193:255-61 (Pubitemid 32524457)
76. Monneret G, Gravel S, Diamond M, et al. Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor. Blood 2001;98:1942-8
77. Gyles SL, Xue L, Townsend ER, et al. A dominant role for chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cells (CRTH2) in mediating chemotaxis of CRTH21CD41Th2 lymphocytes in response to mast cell supernatants. Immunology 2006;119:362-8 (Pubitemid 44571054)
78. Xue L, Barrow A, Pettipher R. Interaction between prostaglandin D2 and chemoattractant receptor-homologous molecule expressed on Th2 cells mediates cytokine production by Th2 lymphocytes in response to activated mast cells. Clin Exp Immunol 2009;156:126-33
79. Xue L, Gyles SL, Wettey FR, et al. Prostaglandin D2 causes preferential induction of proinflammatory Th2 cytokine production through an action on chemoattractant receptor-like molecule expressed on Th2 cells. J Immunol 2005;175:6531-6 (Pubitemid 41598895)
80. Murray JJ, Tonnel AB, Brash AR, et al. Release of prostaglandin D2 into human airways during acute antigen challenge. N Engl J Med 1986;315:800-4 (Pubitemid 16014343)
81. Barnes N, Pavord I, Chuchalin A, et al. A randomized, double-blind, placebo-controlled study of the CRTH2 antagonist OC000459 in moderate persistent asthma. Clin Exp Allergy 2011;42:38-48
82. Fan Chung K. Phosphodiesterase inhibitors in airways disease. Eur J Pharmacol 2006;533:110-17 (Pubitemid 43348344)
83. Diamant Z, Spina D. PDE4-inhibitors: a novel targeted therapy for obstructive airways disease. Pulm Pharmacol Ther 2011;24:353-60
84. Gauvreau GM, Boulet LP, Schmid-Wirlitsch C, et al. Roflumilast attenuates allergen-induced inflammation in mild asthmatic subjects. Respir Res 2011;12:140
85. Heaslip RJ, Evans DY. Emetic, central nervous system, and pulmonary activities of rolipram in the dog. Eur J Pharmacol 1995;286:281-90
86. Torphy TJ, Barnette MS, Underwood DC, et al. Ariflo (SB 207499), a second generation phosphodiesterase 4 inhibitor for the treatment of asthma and COPD: from concept to clinic. Pulm Pharmacol Ther 1999;12:131-5 (Pubitemid 29366508)
87. Kobayashi M, Kubo S, Hirano Y, et al. Anti-asthmatic effect of ASP3258, a novel phosphodiesterase 4 inhibitor. Int Immunopharmacol 2012;12:50-8
88. Shiung YY, Chiang CY, Chen JB, et al. An anti-IgE monoclonal antibody that binds to IgE on CD23 but not on high-affinity IgE Fc receptors. Immunobiology 2011; [Epub ahead of print]
89. Chu SY, Horton HM, Pong E, et al. Reduction of total IgE by targeted coengagement of IgE B-cell receptor and FcgammaRIIb with Fc-engineered antibody. J Allergy Clin Immunol 2012; [Epub ahead of print]
90. Leckie MJ, ten Brinke A, Khan J, et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000;356:2144-8
91. Flood-Page P, Swenson C, Faiferman I, et al. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med 2007;176:1062-71 (Pubitemid 350223751)
92. Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009;360:973-84
93. Nair P, Pizzichini MM, Kjarsgaard M, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 2009;360:985-93
94. Kips JC, O'Connor BJ, Langley SJ, et al. Effect of SCH55700, a humanized anti-human interleukin-5 antibody, in severe persistent asthma: a pilot study. Am J Respir Crit Care Med 2003;167:1655-9 (Pubitemid 36760679)
95. Busse WW, Katial R, Gossage D, et al. Safety profile, pharmacokinetics, and biologic activity of MEDI-563, an anti-IL-5 receptor alpha antibody, in a phase I study of subjects with mild asthma. J Allergy Clin Immunol 2010;125:1237-44
96. Bottema RW, Nolte IM, Howard TD, et al. Interleukin 13 and interleukin 4 receptor-a polymorphisms in rhinitis and asthma. Int Arch Allergy Immunol 2010;153:259-67
97. Oh CK, Geba GP, Molfino N. Investigational therapeutics targeting the IL-4/IL-13/STAT-6 pathway for the treatment of asthma. Eur Respir Rev 2010;19:46-54
98. Borish LC, Nelson HS, Lanz MJ, et al. Interleukin-4 receptor in moderate atopic asthma. A phase I/II randomized, placebo-controlled trial. Am J Respir Crit Care Med 1999;160:1816-23 (Pubitemid 30004681)
99. Borish LC, Nelson HS, Corren J, et al. IL-4R Asthma Study Group. Efficacy of soluble IL-4 receptor for the treatment of adults with asthma. J Allergy Clin Immunol 2001;107:963-70 (Pubitemid 32523334)
100. Hart TK, Blackburn MN, Brigham-Burke M, et al. Preclinical efficacy and safety of pascolizumab (SB 240683): a humanized anti-interleukin-4 antibody with therapeutic potential in asthma. Clin Exp Immunol 2002;130:93-100
101. Gauvreau GM, Boulet LP, Cockcroft DW, et al. Effects of interleukin-13 blockade on allergen-induced airway responses in mild atopic asthma. Am J Respir Crit Care Med 2011;183:1007-14
102. Cockcroft DW, Murdock KY. Comparative effects of inhaled salbutamol, sodium cromoglycate, and beclomethasone dipropionate on allergen-induced early asthmatic responses, late asthmatic responses, and increased bronchial responsiveness to histamine. J Allergy Clin Immunol 1987;79:734-40 (Pubitemid 17074292)
103. Oh CK, Faggioni R, Jin F, et al. An open-label, single-dose bioavailability study of the pharmacokinetics of CAT-354 after subcutaneous and intravenous administration in healthy males. Br J Clin Pharmacol 2010;69:645-55
104. Corren J, Lemanske RF Jr, Hanania NA, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med 2011;365:1088-98
105. Kraft M. Asthma phenotypes and interleukin-13-Moving closer to personalized medicine. N Engl J Med 2011;365:1141-4
106. Shanafelt AB, Forte CP, Kasper JJ, et al. An immune cell-selective interleukin 4 agonist. Proc Natl Acad Sci USA 1998;95:9454-8 (Pubitemid 28506252)
107. Burmeister Getz E, Fisher DM, Fuller R. Human pharmacokinetics/ pharmacodynamics of an interleukin-4 and interleukin-13 dual antagonist in asthma. J Clin Pharmacol 2009;49:1025-36
108. Wenzel S, Wilbraham D, Fuller R, et al. 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 (Pubitemid 47576168)
109. Holgate ST. Pathophysiology of asthma: what has our current understanding taught us about new therapeutic approaches? J Allergy Clin Immunol 2011;128:495-505
110. Slager RE, Hawkins GA, Ampleford EJ, et al. IL-4 receptor a polymorphisms are predictors of a pharmacogenetic response to a novel IL-4/IL-13 antagonist. J Allergy Clin Immunol 2010;126:875-8
111. Holgate ST, Noonan M, Chanez P, et al. Efficacy/safety of etanercept in moderate-to-severe asthma: a randomised, controlled trial. Eur Respir J 2011;37:1352-9
112. Erin EM, Leaker BR, Nicholson GC, et al. The effects of a monoclonal antibody directed against tumor necrosis factor-alpha in asthma. Am J Respir Crit Care Med 2006;174:753-62 (Pubitemid 44511656)
113. Wenzel SE, Barnes PJ, Bleecker ER, 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
114. Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol 2011;127:18-27; quiz 28-9
115. Abramson MJ, Puy RM, Weiner JM. Allergen immunotherapy for asthma. Cochrane Database Syst Rev 2003;4:CD001186
116. Abramson MJ, Puy RM, Weiner JM. Injection allergen immunotherapy for asthma. Cochrane Database Syst Rev 2010;8:CD001186
117. Bahceciler NN, Cobanoglu N. Subcutaneous versus sublingual immunotherapy for allergic rhinitis and/or asthma. Immunotherapy 2011;3:747-56
118. Weiss ST. New approaches to personalized medicine for asthma: where are we? J Allergy Clin Immunol 2012;129:327-34
119. Kramer JM. Balancing the benefits and risks of inhaled long-acting beta-agonists-the influence of values. N Engl J Med 2009;360:1592-5
120. Benyahia C, Gomez I, Kanyinda L, et al. PGE(2) receptor (EP(4)) agonists: Potent dilators of human bronchi and future asthma therapy? Pulm Pharmacol Ther 2012; [Epub ahead of print]
121. Hueber W, Patel DD, Dryja T, et al. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med 2010;2:52-72
122. Antoniu SA. MEDI-528, an anti-IL-9 humanized antibody for the treatment of asthma. Curr Opin Mol Ther 2010;12:233-9
123. Desai D, Brightling C. Cytokine and anti-cytokine therapy in asthma: ready for the clinic? Clin Exp Immunol 2009;158:10-19
124. Rashid R, Frew AJ. Allergen-specific immunotherapy improves asthma symptoms compared with placebo, but the possibility of adverse effects should be considered. Evid Based Med 2011;16:16-17