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Investigational therapies for food allergy: Oral immunotherapy

Author
Anna Nowak-Węgrzyn, MD
Section Editor
Scott H Sicherer, MD, FAAAAI
Deputy Editor
Elizabeth TePas, MD, MS

INTRODUCTION

Food allergy encompasses a variety of immune-mediated adverse reactions to foods that occur in genetically predisposed individuals [1,2]. Management of food allergy consists of strict avoidance of the food allergen and treatment of accidental exposures with medications. Allergies to certain foods, such as egg and milk, tend to be outgrown during childhood, whereas allergies to other foods, such as shellfish and nuts, are much more likely to persist. Oral immunotherapy (OIT) is one of several allergen-specific approaches under investigation for the treatment of food allergy. (See "Management of food allergy: Avoidance" and "Food-induced anaphylaxis" and "Anaphylaxis: Emergency treatment".)

Novel therapeutic approaches to food allergy can be classified as food allergen specific (eg, immunotherapy with native or modified recombinant allergens, or oral desensitization) or food allergen nonspecific (eg, anti-immunoglobulin E [IgE], traditional Chinese medicine [TCM]) (table 1) [3-6]. The goal of these therapies is to induce permanent tolerance to the food, where the allergy will not recur upon re-exposure after a period of abstinence. However, some therapies in development appear to only temporarily desensitize or protect patients, requiring continued treatment to maintain efficacy. Before these new approaches are applied in clinical practice, they must be carefully evaluated for side effects, such as acute adverse reactions, toxicity, and overstimulation of T helper type 1 (Th1) immune responses that could prime for autoimmunity.

OIT for food allergy is reviewed in this topic. Other food allergen-specific therapies as well as nonspecific therapies are reviewed separately. (See "Investigational therapies for food allergy: SLIT, EPIT, SCIT, and nonspecific therapies".)

OVERVIEW OF TREATMENT

OIT to food is generating increasing interest as a potential approach to the treatment of food allergy [7-10]. A high rate of desensitization has been demonstrated in both randomized trials and observational studies of OIT. Fewer treated patients become tolerant, but the rate of acquisition of tolerance is higher than that seen in patients who completely avoid the allergen. Additional long-term follow-up data are needed to help determine which patients will gain the most from OIT and in which patients the risks outweigh the benefits.

Rationale and mechanisms of action — The rationale for using the oral route is that ingestion of a food antigen preferentially results in an active immune system response but one that does not trigger an allergic reaction towards that antigen (ie, oral tolerance) [11,12]. Oral tolerance is thought to be mediated by induction of regulatory T cells with low-dose antigen exposure or lymphocyte anergy or deletion with high antigen doses. (See "Pathogenesis of food allergy", section on 'Factors influencing sensitization or tolerance'.)

                
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Literature review current through: Sep 2017. | This topic last updated: Aug 28, 2017.
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References
Top
  1. Sampson HA. Update on food allergy. J Allergy Clin Immunol 2004; 113:805.
  2. Boyce JA, Assa'ad A, Burks AW, et al. Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report. J Allergy Clin Immunol 2010; 126:1105.
  3. Sicherer SH, Leung DY. Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2007. J Allergy Clin Immunol 2008; 121:1351.
  4. Eigenmann PA, Beyer K, Wesley Burks A, et al. New visions for food allergy: an iPAC summary and future trends. Pediatr Allergy Immunol 2008; 19 Suppl 19:26.
  5. Sicherer SH, Sampson HA. Food allergy: recent advances in pathophysiology and treatment. Annu Rev Med 2009; 60:261.
  6. Nowak-Węgrzyn A, Sampson HA. Future therapies for food allergies. J Allergy Clin Immunol 2011; 127:558.
  7. Rolinck-Werninghaus C, Staden U, Mehl A, et al. Specific oral tolerance induction with food in children: transient or persistent effect on food allergy? Allergy 2005; 60:1320.
  8. Niggemann B, Staden U, Rolinck-Werninghaus C, Beyer K. Specific oral tolerance induction in food allergy. Allergy 2006; 61:808.
  9. Beyer K, Wahn U. Oral immunotherapy for food allergy in children. Curr Opin Allergy Clin Immunol 2008; 8:553.
  10. Vickery BP, Burks W. Oral immunotherapy for food allergy. Curr Opin Pediatr 2010; 22:765.
  11. Ko J, Mayer L. Oral tolerance: lessons on treatment of food allergy. Eur J Gastroenterol Hepatol 2005; 17:1299.
  12. Vickery BP, Burks AW. Immunotherapy in the treatment of food allergy: focus on oral tolerance. Curr Opin Allergy Clin Immunol 2009; 9:364.
  13. Wright BL, Kulis M, Orgel KA, et al. Component-resolved analysis of IgA, IgE, and IgG4 during egg OIT identifies markers associated with sustained unresponsiveness. Allergy 2016; 71:1552.
  14. Burks AW, Jones SM, Wood RA, et al. Oral immunotherapy for treatment of egg allergy in children. N Engl J Med 2012; 367:233.
  15. Syed A, Garcia MA, Lyu SC, et al. Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3). J Allergy Clin Immunol 2014; 133:500.
  16. Glez PP, Franco YB, Matheu V. MIP-1α, MCP-1, and desensitization in anaphylaxis from cow's milk. N Engl J Med 2012; 367:282.
  17. Thyagarajan A, Jones SM, Calatroni A, et al. Evidence of pathway-specific basophil anergy induced by peanut oral immunotherapy in peanut-allergic children. Clin Exp Allergy 2012; 42:1197.
  18. Meglio P, Bartone E, Plantamura M, et al. A protocol for oral desensitization in children with IgE-mediated cow's milk allergy. Allergy 2004; 59:980.
  19. Pajno GB, Caminiti L, Salzano G, et al. Comparison between two maintenance feeding regimens after successful cow's milk oral desensitization. Pediatr Allergy Immunol 2013; 24:376.
  20. Jones SM, Burks AW, Keet C, et al. Long-term treatment with egg oral immunotherapy enhances sustained unresponsiveness that persists after cessation of therapy. J Allergy Clin Immunol 2016; 137:1117.
  21. Meglio P, Giampietro PG, Gianni S, Galli E. Oral desensitization in children with immunoglobulin E-mediated cow's milk allergy--follow-up at 4 yr and 8 months. Pediatr Allergy Immunol 2008; 19:412.
  22. Keet CA, Seopaul S, Knorr S, et al. Long-term follow-up of oral immunotherapy for cow's milk allergy. J Allergy Clin Immunol 2013; 132:737.
  23. Paassilta M, Salmivesi S, Mäki T, et al. Children who were treated with oral immunotherapy for cows' milk allergy showed long-term desensitisation seven years later. Acta Paediatr 2016; 105:215.
  24. Vickery BP, Scurlock AM, Kulis M, et al. Sustained unresponsiveness to peanut in subjects who have completed peanut oral immunotherapy. J Allergy Clin Immunol 2014; 133:468.
  25. Vickery BP, Berglund JP, Burk CM, et al. Early oral immunotherapy in peanut-allergic preschool children is safe and highly effective. J Allergy Clin Immunol 2017; 139:173.
  26. Brożek JL, Terracciano L, Hsu J, et al. Oral immunotherapy for IgE-mediated cow's milk allergy: a systematic review and meta-analysis. Clin Exp Allergy 2012; 42:363.
  27. Jones SM, Pons L, Roberts JL, et al. Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol 2009; 124:292.
  28. Narisety SD, Skripak JM, Steele P, et al. Open-label maintenance after milk oral immunotherapy for IgE-mediated cow's milk allergy. J Allergy Clin Immunol 2009; 124:610.
  29. Varshney P, Jones SM, Scurlock AM, et al. A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response. J Allergy Clin Immunol 2011; 127:654.
  30. Anagnostou K, Islam S, King Y, et al. Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial. Lancet 2014; 383:1297.
  31. Staden U, Rolinck-Werninghaus C, Brewe F, et al. Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy 2007; 62:1261.
  32. Wasserman RL, Factor JM, Baker JW, et al. Oral immunotherapy for peanut allergy: multipractice experience with epinephrine-treated reactions. J Allergy Clin Immunol Pract 2014; 2:91.
  33. Yeung JP, Kloda LA, McDevitt J, et al. Oral immunotherapy for milk allergy. Cochrane Database Syst Rev 2012; 11:CD009542.
  34. Nieto A, Fernandez-Silveira L, Mazon A, Caballero L. Life-threatening asthma reaction caused by desensitization to milk. Allergy 2010; 65:1342.
  35. Varshney P, Steele PH, Vickery BP, et al. Adverse reactions during peanut oral immunotherapy home dosing. J Allergy Clin Immunol 2009; 124:1351.
  36. Hofmann AM, Scurlock AM, Jones SM, et al. Safety of a peanut oral immunotherapy protocol in children with peanut allergy. J Allergy Clin Immunol 2009; 124:286.
  37. Skripak JM, Nash SD, Rowley H, et al. A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy. J Allergy Clin Immunol 2008; 122:1154.
  38. Sánchez-García S, Rodríguez Del Río P, Escudero C, et al. Possible eosinophilic esophagitis induced by milk oral immunotherapy. J Allergy Clin Immunol 2012; 129:1155.
  39. Echeverría-Zudaire LÁ, Fernández-Fernández S, Rayo-Fernández A, et al. Primary eosinophilic gastrointestinal disorders in children who have received food oral immunotherapy. Allergol Immunopathol (Madr) 2016; 44:531.
  40. Ridolo E, De Angelis GL, Dall'aglio P. Eosinophilic esophagitis after specific oral tolerance induction for egg protein. Ann Allergy Asthma Immunol 2011; 106:73.
  41. MacGinnitie AJ, Rachid R, Gragg H, et al. Omalizumab facilitates rapid oral desensitization for peanut allergy. J Allergy Clin Immunol 2017; 139:873.
  42. Patriarca G, Nucera E, Roncallo C, et al. Oral desensitizing treatment in food allergy: clinical and immunological results. Aliment Pharmacol Ther 2003; 17:459.
  43. Lucendo AJ, Arias A, Tenias JM. Relation between eosinophilic esophagitis and oral immunotherapy for food allergy: a systematic review with meta-analysis. Ann Allergy Asthma Immunol 2014; 113:624.
  44. Wood RA, Sampson HA. Oral immunotherapy for the treatment of peanut allergy: is it ready for prime time? J Allergy Clin Immunol Pract 2014; 2:97.
  45. Nurmatov U, Venderbosch I, Devereux G, et al. Allergen-specific oral immunotherapy for peanut allergy. Cochrane Database Syst Rev 2012; :CD009014.
  46. Fisher HR, du Toit G, Lack G. Specific oral tolerance induction in food allergic children: is oral desensitisation more effective than allergen avoidance?: a meta-analysis of published RCTs. Arch Dis Child 2011; 96:259.
  47. Sheikh A, Nurmatov U, Venderbosch I, Bischoff E. Oral immunotherapy for the treatment of peanut allergy: systematic review of six case series studies. Prim Care Respir J 2012; 21:41.
  48. Patriarca C, Romano A, Venuti A, et al. Oral specific hyposensitization in the management of patients allergic to food. Allergol Immunopathol (Madr) 1984; 12:275.
  49. Patriarca G, Schiavino D, Nucera E, et al. Food allergy in children: results of a standardized protocol for oral desensitization. Hepatogastroenterology 1998; 45:52.
  50. Nucera E, Schiavino D, D'Ambrosio C, et al. Immunological aspects of oral desensitization in food allergy. Dig Dis Sci 2000; 45:637.
  51. Patriarca G, Nucera E, Pollastrini E, et al. Oral rush desensitization in peanut allergy: a case report. Dig Dis Sci 2006; 51:471.
  52. Ruëff F, Eberlein-König B, Przybilla B. Oral hyposensitization with celery juice. Allergy 2001; 56:82.
  53. Buchanan AD, Green TD, Jones SM, et al. Egg oral immunotherapy in nonanaphylactic children with egg allergy. J Allergy Clin Immunol 2007; 119:199.
  54. Longo G, Barbi E, Berti I, et al. Specific oral tolerance induction in children with very severe cow's milk-induced reactions. J Allergy Clin Immunol 2008; 121:343.
  55. Morisset M, Moneret-Vautrin DA, Guenard L, et al. Oral desensitization in children with milk and egg allergies obtains recovery in a significant proportion of cases. A randomized study in 60 children with cow's milk allergy and 90 children with egg allergy. Eur Ann Allergy Clin Immunol 2007; 39:12.
  56. Romantsik O, Bruschettini M, Tosca MA, et al. Oral and sublingual immunotherapy for egg allergy. Cochrane Database Syst Rev 2014; :CD010638.
  57. Burks AW, Jones SM. Egg oral immunotherapy in non-anaphylactic children with egg allergy: follow-up. J Allergy Clin Immunol 2008; 121:270.
  58. Vickery BP, Pons L, Kulis M, et al. Individualized IgE-based dosing of egg oral immunotherapy and the development of tolerance. Ann Allergy Asthma Immunol 2010; 105:444.
  59. García Rodríguez R, Urra JM, Feo-Brito F, et al. Oral rush desensitization to egg: efficacy and safety. Clin Exp Allergy 2011; 41:1289.
  60. Burks AW, Laubach S, Jones SM. Oral tolerance, food allergy, and immunotherapy: implications for future treatment. J Allergy Clin Immunol 2008; 121:1344.
  61. Blumchen K, Ulbricht H, Staden U, et al. Oral peanut immunotherapy in children with peanut anaphylaxis. J Allergy Clin Immunol 2010; 126:83.
  62. Anagnostou K, Clark A, King Y, et al. Efficacy and safety of high-dose peanut oral immunotherapy with factors predicting outcome. Clin Exp Allergy 2011; 41:1273.
  63. Bégin P, Winterroth LC, Dominguez T, et al. Safety and feasibility of oral immunotherapy to multiple allergens for food allergy. Allergy Asthma Clin Immunol 2014; 10:1.
  64. Nowak-Wegrzyn A, Bloom KA, Sicherer SH, et al. Tolerance to extensively heated milk in children with cow's milk allergy. J Allergy Clin Immunol 2008; 122:342.
  65. Lemon-Mulé H, Sampson HA, Sicherer SH, et al. Immunologic changes in children with egg allergy ingesting extensively heated egg. J Allergy Clin Immunol 2008; 122:977.
  66. Shreffler WG, Wanich N, Moloney M, et al. Association of allergen-specific regulatory T cells with the onset of clinical tolerance to milk protein. J Allergy Clin Immunol 2009; 123:43.
  67. Giavi S, Vissers YM, Muraro A, et al. Oral immunotherapy with low allergenic hydrolysed egg in egg allergic children. Allergy 2016; 71:1575.
  68. Goldberg MR, Nachshon L, Appel MY, et al. Efficacy of baked milk oral immunotherapy in baked milk-reactive allergic patients. J Allergy Clin Immunol 2015; 136:1601.
  69. Bravin K, Luyt D. Home-Based Oral Immunotherapy With a Baked Egg Protocol. J Investig Allergol Clin Immunol 2016; 26:61.
  70. Nadeau KC, Schneider LC, Hoyte L, et al. Rapid oral desensitization in combination with omalizumab therapy in patients with cow's milk allergy. J Allergy Clin Immunol 2011; 127:1622.
  71. Schneider LC, Rachid R, LeBovidge J, et al. A pilot study of omalizumab to facilitate rapid oral desensitization in high-risk peanut-allergic patients. J Allergy Clin Immunol 2013; 132:1368.
  72. Martorell-Calatayud C, Michavila-Gómez A, Martorell-Aragonés A, et al. Anti-IgE-assisted desensitization to egg and cow's milk in patients refractory to conventional oral immunotherapy. Pediatr Allergy Immunol 2016; 27:544.
  73. Wood RA, Kim JS, Lindblad R, et al. A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy. J Allergy Clin Immunol 2016; 137:1103.
  74. Bégin P, Dominguez T, Wilson SP, et al. Phase 1 results of safety and tolerability in a rush oral immunotherapy protocol to multiple foods using Omalizumab. Allergy Asthma Clin Immunol 2014; 10:7.
  75. Srivastava KD, Siefert A, Fahmy TM, et al. Investigation of peanut oral immunotherapy with CpG/peanut nanoparticles in a murine model of peanut allergy. J Allergy Clin Immunol 2016; 138:536.
  76. Tang ML, Ponsonby AL, Orsini F, et al. Administration of a probiotic with peanut oral immunotherapy: A randomized trial. J Allergy Clin Immunol 2015; 135:737.
  77. Hsiao K-C, Ponsonby A-L, Axelrad C, et al. Long-term clinical and immunological effects of probiotic and peanut oral immunotherapy after treatment cessation: 4-year follow-up of a randomised, double-blind, placebo-controlled trial. The Lancet Child & Adolescent Health 2017.
  78. http://allergen-nce.ca/wp-content/uploads/Chu-Jordana-Waserman-OIT-statement.pdf.