Future Forms of Immunotherapy and Immunomodulators in Allergic Disease

Immunology and Allergy Clinics of North America

Volumn 31, Issue 2, 2011, Pages 343-365

  Nguyen, Tran Hoai T ^a   Stokes, Jeffrey R ^a   Casale, Thomas B ^a  

^a CREIGHTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Allergic rhinitis; Asthma; Cytokine; Immunomodulator; Immunotherapy

Indexed keywords

AIR 645; ALTRAKINCEPT; ANRUKINZUMAB; BAY 169996; BECLOMETASONE DIPROPIONATE; BENRALIZUMAB; BIMOSIAMOSE; CINQUIL; CORTICOSTEROID; CPG OLIGODEOXYNUCLEOTIDE; DACLIZUMAB; ETANERCEPT; GOLIMUMAB; IMMUNOSTIMULATING AGENT; INTERLEUKIN 13; INTERLEUKIN 5 ANTIBODY; INTERLEUKIN 9; LEBRIKIZUMAB; MEDI 528; MEPOLIZUMAB; PASCOLIZUMAB; PHOSPHORYL LIPID A; PIOGLITAZONE; PITRAKINRA; PLACEBO; RESLIZUMAB; ROSIGLITAZONE; SUPLATAST TOSYLATE; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 9; TOLL LIKE RECEPTOR AGONIST; TRALOKINUMAB; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ADAPTIVE IMMUNITY; ALLERGENICITY; ALLERGIC ASTHMA; ALLERGIC DISEASE; ALLERGIC RHINITIS; ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTIGEN PRESENTING CELL; APOPTOSIS; ASTHMA; ATOPIC DERMATITIS; CYTOKINE PRODUCTION; DOSE RESPONSE; DRUG RECEPTOR BINDING; DRUG WITHDRAWAL; ENZYME INHIBITION; EOSINOPHILIC ESOPHAGITIS; FORCED EXPIRATORY VOLUME; HUMAN; IMMUNE RESPONSE; IMMUNOMODULATION; IMMUNOTHERAPY; INNATE IMMUNITY; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; PRIORITY JOURNAL; QUALITY OF LIFE; RESPIRATORY TRACT INFECTION; REVIEW; UNSPECIFIED SIDE EFFECT;

ANIMALS; ANTIBODIES, MONOCLONAL; CYTOKINES; DESENSITIZATION, IMMUNOLOGIC; ENDOTHELIAL CELLS; HUMANS; HYPERSENSITIVITY; IMMUNOGLOBULIN E; IMMUNOLOGIC FACTORS; MEMBRANE GLYCOPROTEINS; TOLL-LIKE RECEPTORS; TRANSCRIPTION FACTORS;

EID: 79955381464     PISSN: 08898561     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.iac.2011.02.003     Document Type: Review

References (131)

1. Krieg A.M. Therapeutic potential of toll-like receptor 9 activation. Nat Rev Drug Discov 2006, 5(6):471-484.
2. Creticos P.S., Schroeder J.T., Hamilton R.G., et al. Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis. N Engl J Med 2006, 355(14):1445-1455.
3. Tulic M.K., Fiset P.O., Christodoulopoulos P., et al. Amb a 1-immunostimulatory oligodeoxynucleotide conjugate immunotherapy decreases the nasal inflammatory response. J Allergy Clin Immunol 2004, 113(2):235-241.
4. Bernstein D., Segall N., Nayak A., et al. Safety and efficacy of the novel vaccine Tolamba in ragweed allergic adults, a dose finding study. J Allergy Clin Immunol 2007, 119(Suppl):S78-S79.
5. Gauvreau G.M., Hessel E.M., Boulet L., et al. Immunostimulatory sequences regulate interferon-inducible genes but not allergic airway responses. Am J Respir Crit Care Med 2006, 174(1):15-20.
6. Senti G., Johansen P., Haug S., et al. Use of A-type CpG oligodeoxynucleotides as an adjuvant in allergen-specific immunotherapy in humans: a phase I/IIa clinical trial. Clin Exp Allergy 2009, 39(4):562-570.
7. Blaziene A., Leisyte P., Sitkauskine B., et al. CYT003-QbG10, a novel allergen-independent immunotherapy, shown to be safe and efficacious in placebo-controlled phase II study. Ann Allergy Asthma Immunol 2009, 102:A19.
8. Placebo-controlled phase II study shows CYT003-QbG10 is safe and efficacious for the treatment of allergic asthma Available at:, Accessed May 10, 2010. http://www.cytos.com/userfiles/file/Cytos_Press_E_100521.pdf.
9. Casale T.B., Kessler J., Romero F.A. Safety of the intranasal toll-like receptor 4 agonist CRX-675 in allergic rhinitis. Ann Allergy Asthma Immunol 2006, 97(4):454-456.
10. Rosewich M., Schulze J., Eickmeier O., et al. Tolerance induction after specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A in children. Clin Exp Immunol 2010, 160(3):403-410.
11. Musarra A., Bignardi D., Troise C., et al. Long-lasting effect of a monophosphoryl lipid-adjuvanted immunotherapy to parietaria. A controlled field study. Eur Ann Allergy Clin Immunol 2010, 42(3):115-119.
12. Rosewich M. Ultra-short course immunotherapy in children and adolescents during a 3-yrs post-marketing surveillance study. Pediatr Allergy Immunol 2010, 21(1 Pt 2):e185-e189.
13. Pfaar O., Barth C., Jaschke C., et al. Sublingual allergen-specific immunotherapy adjuvanted with monophosphoryl lipid A: a phase I/IIa study. Int Arch Allergy Immunol 2010, 154(4):336-344.
14. Tanaka A., Watanabe Y., Ohta S., et al. Suplatast tosilate, a potent anti-allergic agent, inhibits a remodeling in a mouse model of bronchial asthma. Am J Respir Crit Care Med 2010, 181:A5678. 1_MeetingAbstracts.
15. Shimizu S., Hattori R., Majima Y., et al. Th2 cytokine inhibitor suplatast tosilate inhibits antigen-induced mucus hypersecretion in the nasal epithelium of sensitized rats. Ann Otol Rhinol Laryngol 2009, 118(1):67-72.
16. Shahriar M., Mizuguchi H., Maeyama K., et al. Suplatast tosilate inhibits histamine signaling by direct and indirect down-regulation of histamine H1 receptor gene expression through suppression of histidine decarboxylase and IL-4 gene transcriptions. J Immunol 2009, 183(3):2133-2141.
17. Tanaka A., Minoguchi K., Samson K.T., et al. Inhibitory effects of suplatast tosilate on the differentiation and function of monocyte-derived dendritic cells from patients with asthma. Clin Exp Allergy 2007, 37(7):1083-1089.
18. Washio Y., Ohashi Y., Tanaka A., et al. Suplatast tosilate affects the initial increase in specific IgE and interleukin-4 during immunotherapy for perennial allergic rhinitis. Acta Otolaryngol Suppl 1998, 538:126-132.
19. Tamaoki J., Kondo M., Sakai N., et al. Effect of suplatast tosilate, a Th2 cytokine inhibitor, on steroid-dependent asthma: a double-blind randomised study. Lancet 2000, 356(9226):273-278.
20. Wada M., Nagata S., Kudo T., et al. Effect of suplatast tosilate on antileukotriene non-responders with mild-to-moderate persistent asthma. Allergol Int 2009, 58(3):389-393.
21. Hoshino M., Fujita Y., Saji J., et al. Effect of suplatast tosilate on goblet cell metaplasia in patients with asthma. Allergy 2005, 60(11):1394-1400.
22. Sano Y., Suzuki N., Yamada H., et al. Effects of suplatast tosilate on allergic eosinophilic airway inflammation in patients with mild asthma. J Allergy Clin Immunol 2003, 111(5):958-966.
23. Yoshida M., Aizawa H., Inoue H., et al. Effect of suplatast tosilate on airway hyperresponsiveness and inflammation in asthma patients. J Asthma 2002, 39(6):545-552.
24. Miyachi Y., Katayama I., Furue M. Suplatast/tacrolimus combination therapy for refractory facial erythema in adult patients with atopic dermatitis: a meta-analysis study. Allergol Int 2007, 56(3):269-275.
25. Murakami T., Yamanaka K., Tokime K., et al. Topical suplatast tosilate (IPD) ameliorates Th2 cytokine-mediated dermatitis in caspase-1 transgenic mice by downregulating interleukin-4 and interleukin-5. Br J Dermatol 2006, 155(1):27-32.
26. Gauvreau G.M., Boulet L.P., Cockcroft D.W., et al. Antisense therapy against CCR3 and the common beta chain attenuates allergen-induced eosinophilic responses. Am J Respir Crit Care Med 2008, 177(9):952-958.
27. Gauvreau G., Pageau R., Seguin R., et al. Efficacy of increasing doses of TPI ASM8 on allergen inhalation challenges in asthmatics. Am J Respir Crit Care Med 2010, 181:A5669.
28. Fortin M., Moktefi K., Court M., et al. TPI ASM8, an inhaled antisense oligonucleotide drug candidate targeting CCR3 and the common beta chain of IL-3, IL-5 and GM-CSF receptors, potentiates the anti-inflammatory activity of an inhaled corticosteroid in a rat model of asthma. Am J Respir Crit Care Med 2010, 181:A5694.
29. Efficacy of TPI ASM8 during a 14-day allergen challenge Available at:, Accessed July 6, 2010. http://clinicaltrials.gov/ct2/show/NCT01158898.
30. Oldhoff J.M., Darsow U., Werfel T., et al. Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis. Allergy 2005, 60(5):693-696.
31. Straumann A., Conus S., Grzonka P., et al. Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut 2010, 59(01):21-30.
32. Haldar P., Brightling C.E., Hargadon B., et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009, 360(10):973-984.
33. Nair P., Pizzichini M.M., Kjarsgaard M., et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 2009, 360(10):985-993.
34. Walsh G.M. Reslizumab, a humanized anti-IL-5 mAb for the treatment of eosinophil-mediated inflammatory conditions. Curr Opin Mol Ther 2009, 11(3):329-336.
35. Open-label extension study of reslizumab in pediatric subjects with eosinophilic esophagitis Available at:, Accessed May 24, 2010. http://clinicaltrials.gov/show/NCT00635089.
36. Kolbeck R., Kozhich A., Koike M., 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(6):1344-1353. e2.
37. Busse W.W., 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(6):1237-1244. e2.
38. Temann U.A., Ray P., Flavell R.A. Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology. J Clin Invest 2002, 109(1):29-39.
39. Levitt R.C., McLane M.P., MacDonald D., et al. IL-9 pathway in asthma: new therapeutic targets for allergic inflammatory disorders. J Allergy Clin Immunol 1999, 103(5 Pt 2):S485-S491.
40. A study to evaluate the effectiveness and safety of MEDI-528 in adults Available at:, Accessed June 24, 2010. http://clinicaltrials.gov/ct2/show/NCT00968669.
41. Parker J., Brazinsky S., Miller D.S., et al. Randomized, double-blind, placebo-controlled, multicenter phase 2A study to evaluate the effect of a humanized interleukin-9 monoclonal antibody (MEDI-528) on exercise-induced bronchospasm. Am J Respir Crit Care Med 2010, 181:A5394.
42. Borish L.C., Nelson H.S., Corren J., et al. Efficacy of soluble IL-4 receptor for the treatment of adults with asthma. J Allergy Clin Immunol 2001, 107(6):963-970.
43. Bree A., Schlerman F.J., Wadanoli M., et al. IL-13 blockade reduces lung inflammation after Ascaris suum challenge in cynomolgus monkeys. J Allergy Clin Immunol 2007, 119(5):1251-1257.
44. Blanchard C., Mishra A., Saito-Akei H., et al. Inhibition of human interleukin-13-induced respiratory and oesophageal inflammation by anti-human-interleukin-13 antibody (CAT-354). Clin Exp Allergy 2005, 35(8):1096-1103.
45. Kariyawasam H.H., Nicholson G.C., Tan A.J., et al. Effects of anti-IL-13 (Novartis QAX576) on inflammatory responses following nasal allergen challenge (NAC). Am J Respir Crit Care Med 2009, 179:A3642.
46. Efficacy of QAX576 in asthma; 2010. Available at: Accessed June 10, 2010. http://clinicaltrials.gov/ct2/show/NCT01130064%3fterm=QAX576&rank=5.
47. Efficacy and safety of QAX576 in patients with eosinophilic esophagitis Available at:, Accessed September 8, 2010. http://clinicaltrials.gov/ct2/show/NCT01022970%3fterm%3dQAX576%26rank%3d4.
48. Study evaluating the effect of IMA-026 on allergen-induced late asthma response in mild asthma Available at:, Accessed June 1, 2009. http://clinicaltrials.gov/ct2/show/NCT00725582.
49. Study evaluating the effect of IMA-638 in subjects with persistent asthma Available at:, Accessed July 6, 2009. http://clinicaltrials.gov/ct2/show/NCT00425061.
50. Study evaluating the effects of IMA-638 on allergen-induced airway responses in subjects with mild atopic asthma Available at:, Accessed June 26, 2008. http://clinicaltrials.gov/ct2/show/NCT00410280.
51. Oh C.K., 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(6):645-655.
52. Study to evaluate the safety and efficacy of CAT-354.2010. Available at: Accessed April 6, 2010. http://clinicaltrials.gov/ct2/show/NCT00873860.
53. A study of lebrikizumab (MILR1444A) in adult patients with asthma who are inadequately controlled on inhaled corticosteroids (MILLY) Available at:, Accessed June 7, 2010. http://clinicaltrials.gov/ct2/show/NCT00930163.
54. Corren J., Busse W., Meltzer E.O., 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(8):788-796.
55. Hodges M.R., Castelloe E., Chen A., et al. Randomized, double-blind, placebo controlled first in human study of inhaled AIR645, an IL-4Ra oligonucleotide, in healthy volunteers. Am J Respir Crit Care Med 2009, 179:A3640.
56. Study evaluating the effects of AIR 645 on allergen-induced airway responses in subjects with mild atopic asthma Available at:, Accessed July 21, 2010. http://clinicaltrials.gov/ct2/show/NCT00941577.
57. 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(9596):1422-1431.
58. Aeroderm Available at:, Accessed November 2, 2010. http://www.aerovance.com/pipeline/aeroderm/.
59. Busse W.W., Israel E., Nelson H.S., et al. Daclizumab improves asthma control in patients with moderate to severe persistent asthma: a randomized, controlled trial. Am J Respir Crit Care Med 2008, 178(10):1002-1008.
60. Berry M.A., Hargadon B., Shelley M., et al. Evidence of a role of tumor necrosis factor alpha in refractory asthma. N Engl J Med 2006, 354(7):697-708.
61. Wenzel S.E., Barnes P.J., Bleecker E.R., 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(7):549-558.
62. Rossi A.B., Herlaar E., Braselmann S., et al. Identification of the syk kinase inhibitor R112 by a human mast cell screen. J Allergy Clin Immunol 2006, 118(3):749-755.
63. Meltzer E.O., Berkowitz R.B., Grossbard E.B. An intranasal syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment. J Allergy Clin Immunol 2005, 115(4):791-796.
64. Rigel announces disappointing results from phase II study of R112 for the treatment of allergic rhinitis Available at:, Accessed December 1, 2005. http://www.rigel.com/rigel/pr_1133385395.
65. Zhang D.H., Yang L., Cohn L., et al. Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3. Immunity 1999, 11(4):473-482.
66. Woerly G., Honda K., Loyens M., et al. Peroxisome proliferator-activated receptors alpha and gamma down-regulate allergic inflammation and eosinophil activation. J Exp Med 2003, 198(3):411-421.
67. Belvisi M.G., Hele D.J. Peroxisome proliferator-activated receptors as novel targets in lung disease. Chest 2008, 134(1):152-157.
68. Denning G.M., Stoll L.L. Peroxisome proliferator-activated receptors: potential therapeutic targets in lung disease?. Pediatr Pulmonol 2006, 41(1):23-34.
69. Spears M., Donnelly I., Jolly L., et al. Bronchodilatory effect of the PPAR-gamma agonist rosiglitazone in smokers with asthma. Clin Pharmacol Ther 2009, 86(1):49-53.
70. Sandhu M.S., Dimov V., Romero T., et al. Effects of rosiglitazone on airway hyperresponsiveness and obstruction in asthma. J Allergy Clin Immunol 2010, 125(2):AB66.
71. Pilot study of pioglitazone for the treatment of moderate to severe asthma in obese asthmatics (GLITZ) Available at:, Accessed July 7, 2010. http://clinicaltrials.gov/ct2/show/NCT00787644.
72. A randomized, placebo-controlled, double-blind pilot study of pioglitazone hydrochloride in severe, refractory asthma Available at:, Accessed September 17, 2010. http://clinicaltrials.gov/ct2/show/NCT00994175.
73. Karin M., Yamamoto Y., Wang Q.M. The IKK NF-kappa B system: a treasure trove for drug development. Nat Rev Drug Discov 2004, 3(1):17-26.
74. Chiba Y., Todoroki M., Nishida Y., et al. A novel STAT6 inhibitor AS1517499 ameliorates antigen-induced bronchial hypercontractility in mice. Am J Respir Cell Mol Biol 2009, 41(5):516-524.
75. Nguyen T.T., Xie Y., Berro A.I., et al. Relationship of airway hyperresponsiveness and RGS2 expression in asthma. J Allergy Clin Immunol 2011, 127(2):AB55.
76. Beeh K.M., Beier J., Meyer M., et al. Bimosiamose, an inhaled small-molecule pan-selectin antagonist, attenuates late asthmatic reactions following allergen challenge in mild asthmatics: a randomized, double-blind, placebo-controlled clinical cross-over-trial. Pulm Pharmacol Ther 2006, 19(4):233-241.
77. Study to evaluate safety and efficacy of inhaled bimosiamose for the treatment of patients with moderate to severe chronic obstructive pulmonary disease (COPD) Available at:, Accessed May 20, 2010. http://clinicaltrials.gov/ct2/show/NCT01108913.
78. Study to evaluate the effect of bimosiamose on ozone induced sputum neutrophilia Available at:, Accessed January 5, 2010. http://clinicaltrials.gov/ct2/show/NCT00962481.
79. Safety and efficacy study of bimosiamose cream to treat psoriasis Available at:, Accessed August 20, 2009. http://clinicaltrials.gov/ct2/show/NCT00823693.
80. Norris V., Choong L., Tran D., et al. Effect of IVL745, a VLA-4 antagonist, on allergen-induced bronchoconstriction in patients with asthma. J Allergy Clin Immunol 2005, 116(4):761-767.
81. Salter-Cid L.M., Wang E., O'Rourke A.M., et al. Anti-inflammatory effects of inhibiting the amine oxidase activity of semicarbazide-sensitive amine oxidase. J Pharmacol Exp Ther 2005, 315(2):553-562.
82. Xu H.L., Salter-Cid L., Linnik M.D., et al. Vascular adhesion protein-1 plays an important role in postischemic inflammation and neuropathology in diabetic, estrogen-treated ovariectomized female rats subjected to transient forebrain ischemia. J Pharmacol Exp Ther 2006, 317(1):19-29.
83. Madej A., Reich A., Orda A., et al. Expression of vascular adhesion protein-1 in atopic eczema. Int Arch Allergy Immunol 2006, 139(2):114-121.
84. Lin H., Boesel K.M., Griffith D.T., et al. Omalizumab rapidly decreases nasal allergic response and FcepsilonRI on basophils. J Allergy Clin Immunol 2004, 113(2):297-302.
85. Prussin C., Griffith D.T., Boesel K.M., et al. Omalizumab treatment downregulates dendritic cell FcepsilonRI expression. J Allergy Clin Immunol 2003, 112(6):1147-1154.
86. van Rensen E.L., Evertse C.E., van Schadewijk W.A., et al. Eosinophils in bronchial mucosa of asthmatics after allergen challenge: effect of anti-IgE treatment. Allergy 2009, 64(1):72-80.
87. Busse W., Corren J., Lanier B.Q., et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol 2001, 108(2):184-190.
88. Milgrom H., Berger W., Nayak A., et al. Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab). Pediatrics 2001, 108(2):E36.
89. Soler M., Matz J., Townley R., et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J 2001, 18(2):254-261.
90. Corren J., Casale T., Deniz Y., et al. Omalizumab, a recombinant humanized anti-IgE antibody, reduces asthma-related emergency room visits and hospitalizations in patients with allergic asthma. J Allergy Clin Immunol 2003, 111(1):87-90.
91. Wu A.C., Paltiel A.D., Kuntz K.M., et al. Cost-effectiveness of omalizumab in adults with severe asthma: results from the asthma policy model. J Allergy Clin Immunol 2007, 120(5):1146-1152.
92. Casale T.B., Condemi J., LaForce C., et al. Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial. JAMA 2001, 286(23):2956-2967.
93. Hanf G., Noga O., O'Connor A., et al. Omalizumab inhibits allergen challenge-induced nasal response. Eur Respir J 2004, 23(3):414-418.
94. Chervinsky P., Casale T., Townley R., et al. Omalizumab, an anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis. Ann Allergy Asthma Immunol 2003, 91(2):160-167.
95. Subcutaneous omalizumab for treatment of chronic rhinosinusitis with nasal polyposis (Xolair CRS) Available at:, Accessed February 9, 2010. http://clinicaltrials.gov/ct2/show/NCT01066104.
96. Xolair in patients with chronic sinusitis Available at:, Accessed July 16, 2008. http://clinicaltrials.gov/ct2/show/NCT00117611.
97. Kuehr J., Brauburger J., Zielen S., et al. Efficacy of combination treatment with anti-IgE plus specific immunotherapy in polysensitized children and adolescents with seasonal allergic rhinitis. J Allergy Clin Immunol 2002, 109(2):274-280.
98. Casale T.B., Busse W.W., Kline J.N., et al. Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis. J Allergy Clin Immunol 2006, 117(1):134-140.
99. Massanari M., Nelson H., Casale T., et al. Effect of pretreatment with omalizumab on the tolerability of specific immunotherapy in allergic asthma. J Allergy Clin Immunol 2010, 125(2):383-389.
100. A pilot study of the treatment of eosinophilic esophagitis with omalizumab Available at:, Accessed February 2, 2010. http://clinicaltrials.gov/ct2/show/NCT0012360.
101. Omalizumab to treat hyper-IgE (job's) syndrome Available at:, Accessed March 20, 2010. http://clinicaltrials.gov/ct2/show/NCT00260702.
102. A randomized, double-blind, placebo-controlled study of omalizumab for idiopathic anaphylaxis Available at:, Accessed October 1, 2010. http://clinicaltrials.gov/ct2/show/NCT00890162.
103. Identifying responders to Xolair (omalizumab) using eosinophilic esophagitis as a disease model Available at:, Accessed December 28, 2009. http://clinicaltrials.gov/ct2/show/NCT01040598.
104. Omalizumab in the treatment of peanut allergy Available at:, Accessed July 29, 2009. http://clinicaltrials.gov/ct2/show/NCT00949078.
105. An exploratory study to assess multiple doses of omalizumab in patients with cystic fibrosis complicated by ABPA Available at:, Accessed June 24, 2010. http://clinicaltrials.gov/ct2/show/NCT00787917.
106. Lane J.E., Cheyney J.M., Lane T.N., et al. Treatment of recalcitrant atopic dermatitis with omalizumab. J Am Acad Dermatol 2006, 54(1):68-72.
107. Spector S.L., Tan R.A. Effect of omalizumab on patients with chronic urticaria. Ann Allergy Asthma Immunol 2007, 99(2):190-193.
108. A study of Xolair (omalizumab) in patients with chronic idiopathic urticaria (CIU) who remain symptomatic with antihistamine treatment (H1) Available at:, Accessed January 15, 2010. http://clinicaltrials.gov/ct2/show/NCT00866788.
109. Limb S.L., Starke P.R., Lee C.E., et al. Delayed onset and protracted progression of anaphylaxis after omalizumab administration in patients with asthma. J Allergy Clin Immunol 2007, 120(6):1378-1381.
110. Cox L., Platts-Mills T.A., Finegold I., et al. American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force Report on omalizumab-associated anaphylaxis. J Allergy Clin Immunol 2007, 120(6):1373-1377.
111. Wechsler M.E., Wong D.A., Miller M.K., et al. Churg-Strauss syndrome in patients treated with omalizumab. Chest 2009, 136(2):507-518.
112. Poole J.A., Meng J., Reff M., et al. Anti-CD23 monoclonal antibody, lumiliximab, inhibited allergen-induced responses in antigen-presenting cells and T cells from atopic subjects. J Allergy Clin Immunol 2005, 116(4):780-788.
113. Casale T., Busse W., Lizambri R. Results of a phase II, multiple-dose, randomized trial of an anti-CD23 monoclonal antibody (IDEC-152) in patients with seasonal allergic rhinitis. J Allergy Clin Immunol 2003, 111(2):S75.
114. Rosenwasser L.J., Busse W.W., Lizambri R.G., et al. Allergic asthma and an anti-CD23 mAb (IDEC-152): results of a phase I, single-dose, dose-escalating clinical trial. J Allergy Clin Immunol 2003, 112(3):563-570.
115. Wang Y.H., Liu Y.J. OX40-OX40L interactions: a promising therapeutic target for allergic diseases?. J Clin Invest 2007, 117(12):3655-3657.
116. Hoshino A., Tanaka Y., Akiba H., et al. Critical role for OX40 ligand in the development of pathogenic Th2 cells in a murine model of asthma. Eur J Immunol 2003, 33(4):861-869.
117. A study of RO4989991 in patients with allergic rhinitis Available at:, Accessed September 23, 2010. http://clinicaltrials.gov/ct2/show/NCT01152619.
118. A study of huMAb OX40L in the prevention of allergen-induced airway obstruction in adults with mild allergic asthma Available at:, Accessed May 14, 2010. http://clinicaltrials.gov/ct2/show/NCT00983658.
119. Pettipher R. The roles of the prostaglandin D(2) receptors DP(1) and CRTH2 in promoting allergic responses. Br J Pharmacol 2008, 153(Suppl 1):S191-S199.
120. Barnes NB, Pavord IP, Chuchalin AC, et al. A randomised, double-blind, placebo-controlled study of the CRTH2 antagonist OC000459 on moderate persistent asthma [abstract 3267]. European Respiratory Society Annual Meeting. Vienna, Austria, September 15, 2009.
121. Proof of concept study of OC000459 in eosinophilic esophagitis Available at:, Accessed September 1, 2010. http://clinicaltrials.gov/ct2/show/NCT01056783.
122. AMG 853 phase 2 study in subjects with inadequately controlled asthma Available at:, Accessed October 7, 2010. http://clinicaltrials.gov/ct2/show/NCT01018550.
123. Carter L.L., Shiraishi Y., Shin Y., et al. Potent and selective CRTh2 antagonists are efficacious in models of asthma, allergic rhinitis and atopic dermatitis. J Allergy Clin Immunol 2010, 5(2):AB490.
124. Bateman E.D., Izquierdo J.L., Harnest U., et al. Efficacy and safety of roflumilast in the treatment of asthma. Ann Allergy Asthma Immunol 2006, 96(5):679-686.
125. Schmidt B.M., Kusma M., Feuring M., et al. The phosphodiesterase 4 inhibitor roflumilast is effective in the treatment of allergic rhinitis. J Allergy Clin Immunol 2001, 108(4):530-536.
126. van Schalkwyk E., Strydom K., Williams Z., et al. Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, attenuates allergen-induced asthmatic reactions. J Allergy Clin Immunol 2005, 116(2):292-298.
127. Bousquet J., Aubier M., Sastre J., et al. Comparison of roflumilast, an oral anti-inflammatory, with beclomethasone dipropionate in the treatment of persistent asthma. Allergy 2006, 61(1):72-78.
128. Fabbri L.M., Calverley P.M., Izquierdo-Alonso J.L., et al. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. Lancet 2009, 374(9691):695-703.
129. Singh D., Petavy F., Macdonald A.J., et al. The inhaled phosphodiesterase 4 inhibitor GSK256066 reduces allergen challenge responses in asthma. Respir Res 2010, 11:26.
130. A phase II study evaluating intranasal GSK256066 and azelastine hydrochloride in subjects with seasonal allergic rhinitis Available at:, Accessed July 22, 2009. http://clinicaltrials.gov/ct2/show/NCT00612118.
131. A phase II study evaluating intranasal GSK256066 and fluticasone propionate in subjects with seasonal allergic rhinitis (SAR) Available at:, Accessed October 9, 2008. http://clinicaltrials.gov/ct2/show/NCT00612820.