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Anti-IgE therapy

INTRODUCTION

Immunoglobulin E (IgE) plays a central role in the pathogenesis of allergic diseases, including asthma [1]. For this reason, IgE-mediated immunologic pathways have long represented an attractive target for therapeutic agents in asthma and other allergic diseases.

This review will examine IgE neutralization therapy with anti-IgE monoclonal antibody, with a focus on the treatment of asthma. Other promising approaches to reducing IgE, as well as investigational applications of anti-IgE to other disorders, will be discussed briefly. The role of anti-IgE therapy in the overall management of asthma, as recommended by national and international asthma guidelines, is presented separately. The use of anti-IgE in the management of chronic urticaria is also discussed in greater detail elsewhere. (See "An overview of asthma management" and "Chronic urticaria: Treatment of refractory symptoms", section on 'Omalizumab'.)

ROLE OF IgE IN ASTHMA

Most asthmatic patients have elevated circulating immunoglobulin E (IgE) concentrations when levels are adjusted for age [2]. Allergic sensitization results from the formation of specific IgE in response to common inhalant allergens, such as those derived from house dust mites, pollens, animal dander, molds, and cockroaches.

IgE is produced by B lymphocytes under the direction of two cytokines: interleukin (IL)-4 and the closely related IL-13, which are produced by several cell types, including Th2 cells, a subset of T helper lymphocytes prevalent in atopy [3,4]. IgE formation is markedly enhanced by the interaction of two costimulatory molecules: CD40 ligand expressed on Th2 cells and CD40 expressed on B cells. Appropriately stimulated B cells mature into plasma cells that secrete allergen-specific IgE, which circulates and binds to high affinity receptors (Fc-epsilon-RI) on the surface of mast cells, basophils, and other cells. (See "Mast cells: Surface receptors and signal transduction", section on 'High-affinity IgE receptor'.)

Bridging of IgE molecules on mast cells and basophils by protein allergens results in the activation of these cells. Activation leads to release of preformed mediators, such as histamine, and increased synthesis of lipid mediators, such as prostaglandins and cysteinyl-leukotrienes, which in turn, results in bronchoconstriction and plasma exudation [5]. Thus, IgE plays a central role in the mechanism of immediate bronchoconstriction in allergic asthmatic patients after inhalation of allergen. (See "The biology of IgE" and "The relationship between IgE and allergic disease".)

                                     

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Literature review current through: Sep 2014. | This topic last updated: Oct 3, 2014.
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References
Top
  1. Corry DB, Kheradmand F. Induction and regulation of the IgE response. Nature 1999; 402:B18.
  2. Burrows B, Martinez FD, Halonen M, et al. Association of asthma with serum IgE levels and skin-test reactivity to allergens. N Engl J Med 1989; 320:271.
  3. Gauchat JF, Lebman DA, Coffman RL, et al. Structure and expression of germline epsilon transcripts in human B cells induced by interleukin 4 to switch to IgE production. J Exp Med 1990; 172:463.
  4. de Vries JE, Carballido JM, Aversa G. Receptors and cytokines involved in allergic TH2 cell responses. J Allergy Clin Immunol 1999; 103:S492.
  5. Turner H, Kinet JP. Signalling through the high-affinity IgE receptor Fc epsilonRI. Nature 1999; 402:B24.
  6. Tsicopoulos A, Joseph M. The role of CD23 in allergic disease. Clin Exp Allergy 2000; 30:602.
  7. Weinmayr G, Weiland SK, Björkstén B, et al. Atopic sensitization and the international variation of asthma symptom prevalence in children. Am J Respir Crit Care Med 2007; 176:565.
  8. Sears MR, Burrows B, Flannery EM, et al. Relation between airway responsiveness and serum IgE in children with asthma and in apparently normal children. N Engl J Med 1991; 325:1067.
  9. Arbes SJ Jr, Gergen PJ, Vaughn B, Zeldin DC. Asthma cases attributable to atopy: results from the Third National Health and Nutrition Examination Survey. J Allergy Clin Immunol 2007; 120:1139.
  10. Heymann PW, Carper HT, Murphy DD, et al. Viral infections in relation to age, atopy, and season of admission among children hospitalized for wheezing. J Allergy Clin Immunol 2004; 114:239.
  11. Humbert M, Menz G, Ying S, et al. The immunopathology of extrinsic (atopic) and intrinsic (non-atopic) asthma: more similarities than differences. Immunol Today 1999; 20:528.
  12. Zieg G, Lack G, Harbeck RJ, et al. In vivo effects of glucocorticoids on IgE production. J Allergy Clin Immunol 1994; 94:222.
  13. Jabara HH, Brodeur SR, Geha RS. Glucocorticoids upregulate CD40 ligand expression and induce CD40L-dependent immunoglobulin isotype switching. J Clin Invest 2001; 107:371.
  14. Presta LG, Lahr SJ, Shields RL, et al. Humanization of an antibody directed against IgE. J Immunol 1993; 151:2623.
  15. Fick RB Jr. Anti-IgE as novel therapy for the treatment of asthma. Curr Opin Pulm Med 1999; 5:76.
  16. Haselden BM, Kay AB, Larché M. Peptide-mediated immune responses in specific immunotherapy. Int Arch Allergy Immunol 2000; 122:229.
  17. Buhl R. Anti-IgE antibodies for the treatment of asthma. Curr Opin Pulm Med 2005; 11:27.
  18. The Pink Sheet. FDC Reports. Chevy Chase, MD. 2003; 65:26.
  19. Omalizumab (Xolair): an anti-IgE antibody for asthma. Med Lett Drugs Ther 2003; 45:67.
  20. National Asthma Education and Prevention Program: Expert panel report III: Guidelines for the diagnosis and management of asthma. Bethesda, MD: National Heart, Lung, and Blood Institute, 2007. (NIH publication no. 08-4051). www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm (Accessed on March 21, 2011).
  21. Campbell JM, Wofford JD, Knutsen AP. Omalizumab treatment in children 6 to 18 years old with severe asthma at a children's medical center. Pediatr Asthma Allergy Immunol 2008; 21:129.
  22. 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.
  23. Busse W, Spector S, Rosén K, et al. High eosinophil count: a potential biomarker for assessing successful omalizumab treatment effects. J Allergy Clin Immunol 2013; 132:485.
  24. Bousquet J, Wenzel S, Holgate S, et al. Predicting response to omalizumab, an anti-IgE antibody, in patients with allergic asthma. Chest 2004; 125:1378.
  25. Johansson SG, Nopp A, Oman H, et al. The size of the disease relevant IgE antibody fraction in relation to 'total-IgE' predicts the efficacy of anti-IgE (Xolair) treatment. Allergy 2009; 64:1472.
  26. Ankerst J, Nopp A, Johansson SG, et al. Xolair is effective in allergics with a low serum IgE level. Int Arch Allergy Immunol 2010; 152:71.
  27. Olivieri M, Biscardo CA, Turri S, Perbellini L. Omalizumab in persistent severe bakers' asthma. Allergy 2008; 63:790.
  28. Leynadier F, Doudou O, Gaouar H, et al. Effect of omalizumab in health care workers with occupational latex allergy. J Allergy Clin Immunol 2004; 113:360.
  29. Garcia G, Magnan A, Chiron R, et al. A proof-of-concept, randomized, controlled trial of omalizumab in patients with severe, difficult-to-control, nonatopic asthma. Chest 2013; 144:411.
  30. Easthope S, Jarvis B. Omalizumab. Drugs 2001; 61:253.
  31. MacGlashan DW Jr. Releasability of human basophils: cellular sensitivity and maximal histamine release are independent variables. J Allergy Clin Immunol 1993; 91:605.
  32. MacGlashan DW Jr, Bochner BS, Adelman DC, et al. Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody. J Immunol 1997; 158:1438.
  33. Saini SS, MacGlashan DW Jr, Sterbinsky SA, et al. Down-regulation of human basophil IgE and FC epsilon RI alpha surface densities and mediator release by anti-IgE-infusions is reversible in vitro and in vivo. J Immunol 1999; 162:5624.
  34. Beck LA, Marcotte GV, MacGlashan D, et al. Omalizumab-induced reductions in mast cell Fce psilon RI expression and function. J Allergy Clin Immunol 2004; 114:527.
  35. Gomez G, Jogie-Brahim S, Shima M, Schwartz LB. Omalizumab reverses the phenotypic and functional effects of IgE-enhanced Fc epsilonRI on human skin mast cells. J Immunol 2007; 179:1353.
  36. MacGlashan DW Jr, Savage JH, Wood RA, Saini SS. Suppression of the basophil response to allergen during treatment with omalizumab is dependent on 2 competing factors. J Allergy Clin Immunol 2012; 130:1130.
  37. Savage JH, Courneya JP, Sterba PM, et al. Kinetics of mast cell, basophil, and oral food challenge responses in omalizumab-treated adults with peanut allergy. J Allergy Clin Immunol 2012; 130:1123.
  38. Lin H, Boesel KM, Griffith DT, et al. Omalizumab rapidly decreases nasal allergic response and FcepsilonRI on basophils. J Allergy Clin Immunol 2004; 113:297.
  39. Ong YE, Menzies-Gow A, Barkans J, et al. Anti-IgE (omalizumab) inhibits late-phase reactions and inflammatory cells after repeat skin allergen challenge. J Allergy Clin Immunol 2005; 116:558.
  40. Corren J, Shapiro G, Reimann J, et al. Allergen skin tests and free IgE levels during reduction and cessation of omalizumab therapy. J Allergy Clin Immunol 2008; 121:506.
  41. Boulet LP, Chapman KR, Côté J, et al. Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response. Am J Respir Crit Care Med 1997; 155:1835.
  42. Djukanović R, Wilson SJ, Kraft M, et al. Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma. Am J Respir Crit Care Med 2004; 170:583.
  43. Walker S, Monteil M, Phelan K, et al. Anti-IgE for chronic asthma in adults and children. Cochrane Database Syst Rev 2006; :CD003559.
  44. Rodrigo GJ, Neffen H, Castro-Rodriguez JA. Efficacy and safety of subcutaneous omalizumab vs placebo as add-on therapy to corticosteroids for children and adults with asthma: a systematic review. Chest 2011; 139:28.
  45. Solèr M, Matz J, Townley R, et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J 2001; 18:254.
  46. Busse W, Corren J, Lanier BQ, et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol 2001; 108:184.
  47. Fahy JV, Fleming HE, Wong HH, et al. The effect of an anti-IgE monoclonal antibody on the early- and late-phase responses to allergen inhalation in asthmatic subjects. Am J Respir Crit Care Med 1997; 155:1828.
  48. Noga O, Hanf G, Brachmann I, et al. Effect of omalizumab treatment on peripheral eosinophil and T-lymphocyte function in patients with allergic asthma. J Allergy Clin Immunol 2006; 117:1493.
  49. Oliver JM, Tarleton CA, Gilmartin L, et al. Reduced FcepsilonRI-mediated release of asthma-promoting cytokines and chemokines from human basophils during omalizumab therapy. Int Arch Allergy Immunol 2010; 151:275.
  50. Holgate ST, Chuchalin AG, Hébert J, et al. Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Clin Exp Allergy 2004; 34:632.
  51. Lanier B, Bridges T, Kulus M, et al. Omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma. J Allergy Clin Immunol 2009; 124:1210.
  52. Normansell R, Walker S, Milan SJ, et al. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev 2014; 1:CD003559.
  53. Hanania NA, Alpan O, Hamilos DL, et al. Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial. Ann Intern Med 2011; 154:573.
  54. Brodlie M, McKean MC, Moss S, Spencer DA. The oral corticosteroid-sparing effect of omalizumab in children with severe asthma. Arch Dis Child 2012; 97:604.
  55. Corren J, Wood RA, Patel D, et al. Effects of omalizumab on changes in pulmonary function induced by controlled cat room challenge. J Allergy Clin Immunol 2011; 127:398.
  56. Davis LA. Omalizumab: a novel therapy for allergic asthma. Ann Pharmacother 2004; 38:1236.
  57. Hamilton RG, Marcotte GV, Saini SS. Immunological methods for quantifying free and total serum IgE levels in allergy patients receiving omalizumab (Xolair) therapy. J Immunol Methods 2005; 303:81.
  58. Korn S, Haasler I, Fliedner F, et al. Monitoring free serum IgE in severe asthma patients treated with omalizumab. Respir Med 2012; 106:1494.
  59. Hamilton RG. Accuracy of US Food and Drug Administration-cleared IgE antibody assays in the presence of anti-IgE (omalizumab). J Allergy Clin Immunol 2006; 117:759.
  60. Dosing charts are available in the manufacturers prescribing information. Available online at http://www.gene.com/gene/products/information/pdf/xolair-prescribing.pdf (Accessed on April 24, 2014).
  61. Asai N, Ohkuni Y, Komatsu A, et al. Severe persistent asthma responsive to off-label use of omalizumab despite high and low levels of total serum IgE. J Bras Pneumol 2011; 37:567.
  62. Sugino Y, Sanda R, Takagi Y, et al. [A case of severe asthma responsive to omalizumab treatment despite a low serum IgE level and lack of sensitized allergens]. Arerugi 2010; 59:1572.
  63. Fahy JV, Cockcroft DW, Boulet LP, et al. Effect of aerosolized anti-IgE (E25) on airway responses to inhaled allergen in asthmatic subjects. Am J Respir Crit Care Med 1999; 160:1023.
  64. Corne J, Djukanovic R, Thomas L, et al. The effect of intravenous administration of a chimeric anti-IgE antibody on serum IgE levels in atopic subjects: efficacy, safety, and pharmacokinetics. J Clin Invest 1997; 99:879.
  65. Fahy JV. Reducing IgE levels as a strategy for the treatment of asthma. Clin Exp Allergy 2000; 30 Suppl 1:16.
  66. Barnes PJ. Anti-IgE therapy in asthma: rationale and therapeutic potential. Int Arch Allergy Immunol 2000; 123:196.
  67. Menzella F, Facciolongo N, Castagnetti C, et al. Omalizumab: when the non-responder is a late-responder. Eur Ann Allergy Clin Immunol 2009; 41:155.
  68. Slavin RG, Ferioli C, Tannenbaum SJ, et al. Asthma symptom re-emergence after omalizumab withdrawal correlates well with increasing IgE and decreasing pharmacokinetic concentrations. J Allergy Clin Immunol 2009; 123:107.
  69. Nopp A, Johansson SG, Adédoyin J, et al. After 6 years with Xolair; a 3-year withdrawal follow-up. Allergy 2010; 65:56.
  70. Molimard M, Mala L, Bourdeix I, Le Gros V. Observational study in severe asthmatic patients after discontinuation of omalizumab for good asthma control. Respir Med 2014; 108:571.
  71. The Pink Sheet. FDC Reports. Chevy Chase, MD. 2003; 65:18.
  72. Oba Y, Salzman GA. Cost-effectiveness analysis of omalizumab in adults and adolescents with moderate-to-severe allergic asthma. J Allergy Clin Immunol 2004; 114:265.
  73. Wu AC, Paltiel AD, Kuntz KM, et al. Cost-effectiveness of omalizumab in adults with severe asthma: results from the Asthma Policy Model. J Allergy Clin Immunol 2007; 120:1146.
  74. Dal Negro RW, Pradelli L, Tognella S, et al. Cost-utility of add-on omalizumab in difficult-to-treat allergic asthma in Italy. Eur Ann Allergy Clin Immunol 2011; 43:45.
  75. Costello RW, Long DA, Gaine S, et al. Therapy with omalizumab for patients with severe allergic asthma improves asthma control and reduces overall healthcare costs. Ir J Med Sci 2011; 180:637.
  76. Adelroth E, Rak S, Haahtela T, et al. Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen-induced seasonal allergic rhinitis. J Allergy Clin Immunol 2000; 106:253.
  77. Casale TB, Bernstein IL, Busse WW, et al. Use of an anti-IgE humanized monoclonal antibody in ragweed-induced allergic rhinitis. J Allergy Clin Immunol 1997; 100:110.
  78. Mankad VS, Burks AW. Omalizumab : other indications and unanswered questions. Clin Rev Allergy Immunol 2005; 29:17.
  79. Kopp MV, Stenglein S, Kamin W, et al. Omalizumab (Xolair) in children with seasonal allergic rhinitis: leukotriene release as a potential in vitro parameter to monitor therapeutic effects. Pediatr Allergy Immunol 2007; 18:523.
  80. Casale TB, Condemi J, LaForce C, et al. Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial. JAMA 2001; 286:2956.
  81. Kontou-Fili K. High omalizumab dose controls recurrent reactions to venom immunotherapy in indolent systemic mastocytosis. Allergy 2008; 63:376.
  82. 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; 125:383.
  83. Casale TB, Busse WW, Kline JN, et al. Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis. J Allergy Clin Immunol 2006; 117:134.
  84. Stock P, Rolinck-Werninghaus C, Wahn U, Hamelmann E. The role of anti-IgE therapy in combination with allergen specific immunotherapy for seasonal allergic rhinitis. BioDrugs 2007; 21:403.
  85. Leung DY, Sampson HA, Yunginger JW, et al. Effect of anti-IgE therapy in patients with peanut allergy. N Engl J Med 2003; 348:986.
  86. Giavina-Bianchi P, Giavina-Bianchi M, Agondi R, Kalil J. Three months' administration of anti-IgE to a patient with Churg-Strauss syndrome. J Allergy Clin Immunol 2007; 119:1279; author reply 1279.
  87. Penn R, Mikula S. The role of anti-IgE immunoglobulin therapy in nasal polyposis: a pilot study. Am J Rhinol 2007; 21:428.
  88. Fairley JA, Baum CL, Brandt DS, Messingham KA. Pathogenicity of IgE in autoimmunity: successful treatment of bullous pemphigoid with omalizumab. J Allergy Clin Immunol 2009; 123:704.
  89. Pérez-de-Llano LA, Vennera MC, Parra A, et al. Effects of omalizumab in Aspergillus-associated airway disease. Thorax 2011; 66:539.
  90. Sampson HA, Leung DY, Burks AW, et al. A phase II, randomized, double‑blind, parallel‑group, placebo‑controlled oral food challenge trial of Xolair (omalizumab) in peanut allergy. J Allergy Clin Immunol 2011; 127:1309.
  91. Lehmann S, Pfannenstiel C, Friedrichs F, et al. Omalizumab: a new treatment option for allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. Ther Adv Respir Dis 2014; 8:141.
  92. Beck LA, Saini S. Wanted: A study with omalizumab to determine the role of IgE-mediated pathways in atopic dermatitis. J Am Acad Dermatol 2006; 55:540.
  93. Vigo PG, Girgis KR, Pfuetze BL, et al. Efficacy of anti-IgE therapy in patients with atopic dermatitis. J Am Acad Dermatol 2006; 55:168.
  94. Sheinkopf LE, Rafi AW, Do LT, et al. Efficacy of omalizumab in the treatment of atopic dermatitis: a pilot study. Allergy Asthma Proc 2008; 29:530.
  95. Forman SB, Garrett AB. Success of omalizumab as monotherapy in adult atopic dermatitis: case report and discussion of the high-affinity immunoglobulin E receptor, FcepsilonRI. Cutis 2007; 80:38.
  96. Krathen RA, Hsu S. Failure of omalizumab for treatment of severe adult atopic dermatitis. J Am Acad Dermatol 2005; 53:338.
  97. Schmitt J, Schäkel K. [Omalizumab as a therapeutic option in atopic eczema. Current evidence and potential benefit]. Hautarzt 2007; 58:128, 130.
  98. Heil PM, Maurer D, Klein B, et al. Omalizumab therapy in atopic dermatitis: depletion of IgE does not improve the clinical course - a randomized, placebo-controlled and double blind pilot study. J Dtsch Dermatol Ges 2010; 8:990.
  99. Genentech, Inc. Omalizumab (Xolair) Review of clinical safety data. www.fda.gov/ohrms/dockets/ac/03/briefing/3952B1_02_FDA-Xolair-Safety.pdf (Accessed on April 27, 2006).
  100. Deniz YM, Gupta N. Safety and tolerability of omalizumab (Xolair), a recombinant humanized monoclonal anti-IgE antibody. Clin Rev Allergy Immunol 2005; 29:31.
  101. Lin RY, Rodriguez-Baez G, Bhargave GA. Omalizumab-associated anaphylactic reactions reported between January 2007 and June 2008. Ann Allergy Asthma Immunol 2009; 103:442.
  102. Corren J, Casale TB, Lanier B, et al. Safety and tolerability of omalizumab. Clin Exp Allergy 2009; 39:788.
  103. Cox L, Platts-Mills TA, 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; 120:1373.
  104. Cox L, Lieberman P, Wallace D, et al. American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma & Immunology Omalizumab-Associated Anaphylaxis Joint Task Force follow-up report. J Allergy Clin Immunol 2011; 128:210.
  105. Price KS, Hamilton RG. Anaphylactoid reactions in two patients after omalizumab administration after successful long-term therapy. Allergy Asthma Proc 2007; 28:313.
  106. United States Food and Drug Administration. 2007 Safety alerts for drug, biologics, medical devices, and dietary supplements. www.fda.gov/medwatch/safety/2007/safety07.htm#Xolair (Accessed on January 29, 2008).
  107. Limb SL, Starke PR, Lee CE, Chowdhury BA. Delayed onset and protracted progression of anaphylaxis after omalizumab administration in patients with asthma. J Allergy Clin Immunol 2007; 120:1378.
  108. Lieberman P, Rahmaoui A, Wong DA. The safety and interpretability of skin tests with omalizumab. Ann Allergy Asthma Immunol 2010; 105:493.
  109. Owens G, Petrov A. Successful desensitization of three patients with hypersensitivity reactions to omalizumab. Curr Drug Saf 2011; 6:339.
  110. Dreyfus DH, Randolph CC. Characterization of an anaphylactoid reaction to omalizumab. Ann Allergy Asthma Immunol 2006; 96:624.
  111. Pilette C, Coppens N, Houssiau FA, Rodenstein DO. Severe serum sickness-like syndrome after omalizumab therapy for asthma. J Allergy Clin Immunol 2007; 120:972.
  112. Omalizumab (marketed as Xolair) - Early communication about an ongoing safety review. Available on the website of the U.S. Department of Health and Human Services. www.accessdata.fda.gov/scripts/cder/drugsatfda/ (Accessed on August 19, 2009).
  113. United States Food and Drug Administration (FDA) release. http://www.fda.gov/Drugs/DrugSafety/ucm414911.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery (Accessed on September 30, 2014).
  114. Korenaga M, Watanabe N, Tada I. Effects of anti-IgE monoclonal antibody on a primary infection of Strongyloides ratti in mice. Parasitol Res 1991; 77:362.
  115. Amiri P, Haak-Frendscho M, Robbins K, et al. Anti-immunoglobulin E treatment decreases worm burden and egg production in Schistosoma mansoni-infected normal and interferon gamma knockout mice. J Exp Med 1994; 180:43.
  116. Cruz AA, Lima F, Sarinho E, et al. Safety of anti-immunoglobulin E therapy with omalizumab in allergic patients at risk of geohelminth infection. Clin Exp Allergy 2007; 37:197.
  117. Busse W, Buhl R, Fernandez Vidaurre C, et al. Omalizumab and the risk of malignancy: results from a pooled analysis. J Allergy Clin Immunol 2012; 129:983.
  118. Long A, Rahmaoui A, Rothman KJ, et al. Incidence of malignancy in patients with moderate-to-severe asthma treated with or without omalizumab. J Allergy Clin Immunol 2014; 134:560.
  119. Kupryś-Lipińska I, Tworek D, Kuna P. Omalizumab in pregnant women treated due to severe asthma: two case reports of good outcomes of pregnancies. Postepy Dermatol Alergol 2014; 31:104.
  120. Hirashima J, Hojo M, Iikura M, et al. [A case of an asthma patient receiving omalizumab during pregnancy]. Arerugi 2012; 61:1683.
  121. Cohen ES, Dobson CL, Käck H, et al. A novel IgE-neutralizing antibody for the treatment of severe uncontrolled asthma. MAbs 2014; 6:756.
  122. Rosenwasser LJ, Meng J. Anti-CD23. Clin Rev Allergy Immunol 2005; 29:61.
  123. Rosenwasser LJ, Busse WW, Lizambri RG, 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; 112:563.
  124. 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.
  125. Ichinose M, Barnes PJ. Cytokine-directed therapy in asthma. Curr Drug Targets Inflamm Allergy 2004; 3:263.
  126. 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.
  127. Corren J, Lemanske RF, Hanania NA, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med 2011; 365:1088.
  128. Bryan SA, O'Connor BJ, Matti S, et al. Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000; 356:2149.
  129. Boguniewicz M, Martin RJ, Martin D, et al. The effects of nebulized recombinant interferon-gamma in asthmatic airways. J Allergy Clin Immunol 1995; 95:133.