Improving Safety in Food Allergen-Specific Oral Immunotherapy
Source abstract
Abstract
Food allergies are becoming more common globally. The strict elimination diet, as the main approach so far, has a negative impact on different areas of the lives of children suffering from food allergies, as well as on their caregivers. Oral immunotherapy (OIT), which consists of ingesting small, gradually increasing amounts of food allergens, is a promising approach. Although efficient, this approach is accompanied by frequent adverse reactions (AR), some of which are as severe as anaphylaxis. It seems that, generally, slow dose escalation, as well as low maintenance doses with longer durations, make OIT safer, especially in children with severe food allergies. Furthermore, less allergenic forms of allergens, such as baked milk or egg, also contribute to OIT safety. Adjuvant therapy in combination with OIT has the potential to improve OIT efficiency and safety. Treatment with monoclonal antibodies such as omalizumab and dupilumab in combination with OIT is promising. While both could improve efficiency, omalizumab seems to have a better effect on safety. Interferon γ shows promising results. In contrast, the effect of probiotics and vitamin D supplementation in combination with OIT is still controversial, and new trials about their synergistic effect are needed.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Food Allergy and Anaphylaxis Research · Allergic Rhinitis and Sensitization · Contact Dermatitis and Allergies
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Srebrnjak Children’s Hospital, Srebrnjak 100, HR-10000 Zagreb, Croatia
Faculty of Medicine, J.J. Strossmayer University of Osijek, HR-31000 Osijek, Croatia
Srebrnjak Children’s Hospital, University North, Jurja Križanića 31b, HR-42000 Varaždin, Croatia
Prima Nova, Healthcare Institution, Zagrebačka Cesta 132A, HR-10000 Zagreb, Croatia
References (95)
Show source-provided references
1. Prevalence of Food Sensitization and Food Allergy in Children Across Europe10.1016/j.jaip.2020.04.020 ↗
2. EAACI Guidelines on the Management of IgE-mediated Food Allergy10.1111/all.16345 ↗
3. A case of egg poisoning10.1016/S0140-6736(00)67313-0 ↗
4. Variations in Protocol Development during Oral Immunotherapy10.2500/jfa.2022.4.220002 ↗
5. EAACI Guidelines on Allergen Immunotherapy: IgE-mediated Food Allergy10.1111/all.13319 ↗
6. Weighing the Benefits and Risks of Oral Immunotherapy in Clinical Practice10.2500/aap.2021.42.200107 ↗
7. Flom, J.D., and Sicherer, S.H. (2019). Epidemiology of Cow’s Milk Allergy. Nutrients, 11.10.3390/nu11051051 ↗
8. Nutritional Risks in Children with Food Allergy10.55730/1300-0144.5648 ↗
9. Feeding Difficulties in Children with Food Allergies: An EAACI Task Force Report10.1111/pai.14119 ↗
10. A Randomized, Double-Blind, Placebo-Controlled Study of Milk Oral Immunotherapy for Cow’s Milk Allergy10.1016/j.jaci.2008.09.030 ↗
11. Open-Label Maintenance after Milk Oral Immunotherapy for IgE-Mediated Cow’s Milk Allergy10.1016/j.jaci.2009.06.025 ↗
12. Specific Oral Tolerance Induction in Children with Very Severe Cow’s Milk-Induced Reactions10.1016/j.jaci.2007.10.029 ↗
13. Effect of Oral Immunotherapy in Children with Milk Allergy: The ORIMA Study10.1016/j.alit.2020.09.011 ↗
14. A Single-Center, Case-Control Study of Low-Dose-Induction Oral Immunotherapy with Cow’s Milk10.1159/000442157 ↗
15. Slow Low-Dose Oral Immunotherapy: Threshold and Immunological Change10.1016/j.alit.2020.03.008 ↗
16. Tolerance to Extensively Heated Milk in Children with Cow’s Milk Allergy10.1016/j.jaci.2008.05.043 ↗
17. Rare, Medium, or Well Done? The Effect of Heating and Food Matrix on Food Protein Allergenicity10.1097/ACI.0b013e32832b88e7 ↗
18. Increased Tolerance to Less Extensively Heat-Denatured (Baked) Milk Products in Milk-Allergic Children10.1016/j.jaip.2017.10.021 ↗
19. A Randomized Trial of Oral Immunotherapy for Pediatric Cow’s Milk-Induced Anaphylaxis: Heated vs Unheated Milk10.1111/pai.13352 ↗
20. Efficacy and Safety of Baked Milk Oral Immunotherapy in Children with Severe Milk Allergy: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial10.1016/j.jaci.2021.10.023 ↗
21. Oral Immunotherapy Using Partially Hydrolyzed Formula for Cow’s Milk Protein Allergy: A Randomized, Controlled Trial10.1159/000490804 ↗
22. Clinical and Immunological Outcomes after Randomized Trial of Baked Milk Oral Immunotherapy for Milk Allergy10.1172/jci.insight.184301 ↗
23. International Survey on Growth Indices and Impacting Factors in Children with Food Allergies10.1111/jhn.12610 ↗
24. Egg Oral Immunotherapy in Nonanaphylactic Children with Egg Allergy10.1016/j.jaci.2006.09.016 ↗
25. Oral Immunotherapy for Treatment of Egg Allergy in Children10.1056/NEJMoa1200435 ↗
26. Oral Immunotherapy for Egg Allergy: A Double-Blind Placebo-Controlled Study, with Postdesensitization Follow-Up10.1016/j.jaip.2015.01.017 ↗
27. Long-Term Treatment with Egg Oral Immunotherapy Enhances Sustained Unresponsiveness That Persists after Cessation of Therapy10.1016/j.jaci.2015.12.1316 ↗
28. Efficacy and Safety of High-Dose Rush Oral Immunotherapy in Persistent Egg Allergic Children10.1016/j.anai.2016.11.023 ↗
29. Desensitization to a Whole Egg by Rush Oral Immunotherapy Improves the Quality of Life of Guardians: A Multicenter, Randomized, Parallel-Group, Delayed-Start Design Study10.1016/j.alit.2017.07.007 ↗
30. Egg OIT in Clinical Practice (SEICAP II): Maintenance Patterns and Desensitization State after Normalizing the Diet10.1111/pai.13002 ↗
31. Induction of Sustained Unresponsiveness after Egg Oral Immunotherapy Compared to Baked Egg Therapy in Children with Egg Allergy10.1016/j.jaci.2020.05.040 ↗
32. A 5-Year Summary of Real-Life Dietary Egg Consumption after Completion of a 4-Year Egg Powder Oral Immunotherapy (EOIT) Protocol10.1016/j.jaci.2019.11.045 ↗
33. A Randomized, Open-Label Trial of Hen’s Egg Oral Immunotherapy: Efficacy and Humoral Immune Responses in 50 Children10.1016/j.jaip.2021.01.020 ↗
34. Evaluation of Oral Immunotherapy Efficacy and Safety by Maintenance Dose Dependency: A Multicenter Randomized Study10.1016/j.waojou.2020.100463 ↗
35. The Global Burden of Illness of Peanut Allergy: A Comprehensive Literature Review10.1111/all.14666 ↗
36. Peanut Oral Immunotherapy: Current Trends in Clinical Trials10.1093/immadv/ltac004 ↗
37. Early Oral Immunotherapy in Peanut-Allergic Preschool Children Is Safe and Highly Effective10.1016/j.jaci.2016.05.027 ↗
38. Efficacy and Safety of Oral Immunotherapy in Children Aged 1–3 Years with Peanut Allergy (the Immune Tolerance Network IMPACT Trial): A Randomised Placebo-Controlled Study10.1016/S0140-6736(21)02390-4 ↗
39. Assessing the Efficacy of Oral Immunotherapy for the Desensitisation of Peanut Allergy in Children (STOP II): A Phase 2 Randomised Controlled Trial10.1016/S0140-6736(13)62301-6 ↗
40. A Review of Shared Decision-Making, Published Protocols, and Post-Desensitization Strategies in Oral Immunotherapy (OIT)10.1007/s11882-024-01132-2 ↗
41. A Randomized Controlled Study of Peanut Oral Immunotherapy: Clinical Desensitization and Modulation of the Allergic Response10.1016/j.jaci.2010.12.1111 ↗
42. Efficacy and Safety of AR101 in Oral Immunotherapy for Peanut Allergy: Results of ARC001, a Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial10.1016/j.jaip.2017.09.016 ↗
43. PALISADE Group of Clinical Investigators (2018). AR101 Oral Immunotherapy for Peanut Allergy. N. Engl. J. Med., 379, 1991–2001.10.1056/NEJMoa1812856 ↗
44. Continuous and Daily Oral Immunotherapy for Peanut Allergy: Results from a 2-Year Open-Label Follow-On Study10.1016/j.jaip.2020.12.029 ↗
45. Open-label Follow-on Study Evaluating the Efficacy, Safety, and Quality of Life with Extended Daily Oral Immunotherapy in Children with Peanut Allergy10.1111/all.15027 ↗
46. Oral Immunotherapy for Peanut Allergy in Children 1 to Less Than 4 Years of Age
47. Sustained Outcomes in Oral Immunotherapy for Peanut Allergy (POISED Study): A Large, Randomised, Double-Blind, Placebo-Controlled, Phase 2 Study10.1016/S0140-6736(19)31793-3 ↗
48. Food Allergen Immunotherapy: Current Status and Prospects for the Future10.1016/j.jaci.2016.01.001 ↗
49. An Update on Oral Immunotherapy for the Treatment of Food Allergy10.1016/j.paed.2016.03.004 ↗
50. Adjuvant Therapies in Food Immunotherapy10.1016/j.iac.2017.09.008 ↗
51. Adverse Effects during Specific Oral Tolerance Induction: In Home Phase10.1016/j.aller.2011.05.004 ↗
52. Long-Term Follow-up of Oral Immunotherapy for Cow’s Milk Allergy10.1016/j.jaci.2013.05.006 ↗
53. Omalizumab Treatment Downregulates Dendritic Cell FcεRI Expression10.1016/j.jaci.2003.10.003 ↗
54. Effect of Anti-IgE Therapy in Patients with Peanut Allergy10.1056/NEJMoa022613 ↗
55. A Phase II, Randomized, Double-blind, Parallel-group, Placebo-controlled Oral Food Challenge Trial of Xolair (Omalizumab) in Peanut Allergy10.1016/j.jaci.2011.01.051 ↗
56. Kinetics of Mast Cell, Basophil, and Oral Food Challenge Responses in Omalizumab-Treated Adults with Peanut Allergy10.1016/j.jaci.2012.05.039 ↗
57. Rapid Oral Desensitization in Combination with Omalizumab Therapy in Patients with Cow’s Milk Allergy10.1016/j.jaci.2011.04.009 ↗
58. Long-Term Outcome of Peanut Oral Immunotherapy Facilitated Initially by Omalizumab10.1016/j.jaip.2018.09.015 ↗
59. Omalizumab Facilitates Rapid Oral Desensitization for Peanut Allergy10.1016/j.jaci.2016.08.010 ↗
60. A Pilot Study of Omalizumab to Facilitate Rapid Oral Desensitization in High-Risk Peanut-Allergic Patients10.1016/j.jaci.2013.09.046 ↗
61. Phase 1 Results of Safety and Tolerability in a Rush Oral Immunotherapy Protocol to Multiple Foods Using Omalizumab10.1186/1710-1492-10-7 ↗
62. Oral Immunotherapy Combined with Omalizumab for High–Risk Cow’s Milk Allergy: A Randomized Controlled Trial10.1038/s41598-017-16730-6 ↗
63. Possible Recurrence of Symptoms after Discontinuation of Omalizumab in Anti-IgE-assisted Desensitization to Egg10.1111/pai.12259 ↗
64. Observational Long-Term Follow-up Study of Rapid Food Oral Immunotherapy with Omalizumab10.1186/s13223-017-0223-8 ↗
65. A Phase 2 Randomized Controlled Multisite Study Using Omalizumab-Facilitated Rapid Desensitization to Test Continued vs Discontinued Dosing in Multifood Allergic Individuals10.1016/j.eclinm.2018.12.006 ↗
66. Precise and in Situ Genetic Humanization of 6 Mb of Mouse Immunoglobulin Genes10.1073/pnas.1323896111 ↗
67. Mice with Megabase Humanization of Their Immunoglobulin Genes Generate Antibodies as Efficiently as Normal Mice10.1073/pnas.1324022111 ↗
68. Commonality of the IL-4/IL-13 Pathway in Atopic Diseases10.1080/1744666X.2017.1298443 ↗
69. Dual Blockade of IL-4 and IL-13 with Dupilumab, an IL-4Rα Antibody, Is Required to Broadly Inhibit Type 2 Inflammation10.1111/all.14151 ↗
70. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis10.1056/NEJMoa1610020 ↗
71. Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma10.1056/NEJMoa1804092 ↗
72. Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis10.1056/NEJMoa2205982 ↗
73. Efficacy of Dupilumab on Clinical Outcomes in Patients with Asthma and Perennial Allergic Rhinitis10.1016/j.anai.2020.05.026 ↗
74. Dupilumab as an Adjunct to Oral Immunotherapy in Pediatric Patients with Peanut Allergy10.1111/all.16420 ↗
75. The Role of Interferon-Gamma on Immune and Allergic Responses10.1590/S0074-02762005000900024 ↗
76. Pilot study of ifn-γ-induced specific hyposensitization for house dust mites in atopic dermatitis: Ifn-γ-induced immune deviation as a new therapeutic concept for atopic dermatitis10.1006/cyto.1999.0589 ↗
77. Marone, G. (2003). Effects of IFN-γ on Milk-Specific Oral Tolerance Induction for Milk Allergy in Atopic Dermatitis: Food-Specific Oral Tolerance Induction Using IFN-γ as Adjuvant. Clinical Immunology and Allergy in Medicine, JGC Editions.
78. Dual Specific Oral Tolerance Induction Using Interferon Gamma for IgE-Mediated Anaphylactic Food Allergy and the Dissociation of Local Skin Allergy and Systemic Oral Allergy: Tolerance or Desensitization?
79. A Pilot Study of Interferon-γ–Induced Specific Oral Tolerance Induction (ISOTI) for Immunoglobulin E–Mediated Anaphylactic Food Allergy10.1089/jir.2009.0001 ↗
80. Asthma Prevention by Lactobacillus rhamnosus in a Mouse Model Is Associated with CD4 + CD25 + Foxp3 + T Cells10.4168/aair.2012.4.3.150 ↗
81. Lactobacillus gasseri Suppresses Th17 pro-Inflammatory Response and Attenuates Allergen-Induced Airway Inflammation in a Mouse Model of Allergic Asthma10.1017/S0007114511005265 ↗
82. Generation of Regulatory Dendritic Cells and CD4 + Foxp3 + T Cells by Probiotics Administration Suppresses Immune Disorders10.1073/pnas.0904055107 ↗
83. Administration of a Probiotic with Peanut Oral Immunotherapy: A Randomized Trial10.1016/j.jaci.2014.11.034 ↗
84. The Longitudinal Impact of Probiotic and Peanut Oral Immunotherapy on Health-related Quality of Life10.1111/all.13330 ↗
85. 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 Trial10.1016/S2352-4642(17)30041-X ↗
86. Vitamin D and the Development of Allergic Disease: How Important Is It?10.1111/cea.12430 ↗
87. Vitamin D for Health: A Global Perspective10.1016/j.mayocp.2013.05.011 ↗
88. Vitamin D, the Cutaneous Barrier, Antimicrobial Peptides and Allergies: Is There a Link?10.4168/aair.2013.5.3.119 ↗
89. de C.; Silva, G.A.P. da; Sarinho, E.S.C.; Brandt, K.G. Do Infants with Cow’s Milk Protein Allergy Have Inadequate Levels of Vitamin D?10.1016/j.jped.2017.01.006 ↗
90. Vitamin D Insufficiency Is Associated with Challenge-Proven Food Allergy in Infants10.1016/j.jaci.2013.01.017 ↗
91. Clinical Efficacy of Vitamin D3 Adjuvant Therapy in Allergic Rhinitis: A Randomized Controlled Trial
92. Food-Induced Anaphylaxis10.1016/j.iac.2011.10.002 ↗
93. High- and Low-dose Oral Immunotherapy Similarly Suppress Pro-allergic Cytokines and Basophil Activation in Young Children10.1111/cea.13256 ↗
94. Kirsten, P. (2021). Low Dose Multi-Nut Oral Immunotherapy in Pre-Schoolers with a Multi-Nut Allergy (LMNOP). Clinical Trial NCT05049512, manuscript in preparation.
95. Gut Microbiota and Allergic Diseases in Children10.1016/j.alit.2022.02.004 ↗