Low-dose Oral Immunotherapy Research Articles

Low-dose oral immunotherapy for children with anaphylactic peanut allergy in Japan.

Oral immunotherapy (OIT) is a promising treatment for persons with allergy; however, it can also cause adverse allergic reactions. In this study, we investigated the efficacy of low-dose OIT for anaphylactic peanut allergy. Twenty-four children (median age, 9.6years) with anaphylaxis to peanuts were hospitalized for 5days and then gradually fed increasing amounts of peanut powder up to 133mg/day. One year later, they underwent an oral food challenge after 2weeks of peanut avoidance. Those who were asymptomatic after ingesting 795mg of peanut protein were defined as having achieved sustained unresponsiveness. We measured peanut- and Ara h2-specific immunoglobulin (Ig) E, IgG, and IgG4 levels at 0, 1, 3, 6, and 12months in the OIT group and at 0 and 12months in the control group. At baseline, all children in the OIT group and 8 in the control group had a history of anaphylaxis. The median peanut-/Ara h2-specific IgE levels in the OIT and control groups were 55.4/48.6 and 58.2/38.1kUa/L, respectively. One year later, 8 (33.3%) children in the OIT group exhibited sustained unresponsiveness, while none in the control group did. In the OIT group, the median peanut-specific IgE levels significantly increased to 194.0kUa/L, after 1month and then significantly decreased to 57.5kUa/L at 12months. Meanwhile, the median peanut- and Ara h2-specific IgG and IgG4 levels increased significantly after 1month. Low-dose OIT induces immunological changes and has the capability of achieving sustained unresponsiveness in children with peanut anaphylaxis.

Low-Dose Oral Immunotherapy Using Low-Egg-Allergen Cookies for Severe Egg-Allergic Children Reduces Allergy Severity and Affects Allergen-Specific Antibodies in Serum

Background: We evaluated the safety and efficacy of low-egg-allergen cookies (LAC) as low-dose oral immunotherapy (OIT) in children with severe egg allergy. We also examined the relationship between mild desensitization by low-dose OIT and serum biomarkers of allergy. Methods: We enrolled 13 children with egg allergy who could not receive OIT with hard-boiled egg white (EW). For 11 participants, OIT was carried out using LAC for 3-4 months. Open food challenges with hard-boiled EW and blood samplings were performed before and after OIT. Participants were divided into 2 groups: high effect (H-E) and no/low effect (N/L-E). Serum levels of total IgE and egg yolk-, EW-, and ovomucoid (OM)-specific IgE, ovalbumin (OVA)- and OM-specific IgG₄, IgA₁, and IgA₂, and the percentage of CD 203c⁺ were measured. Results: Allergic severity was reduced in 7 patients, who were assigned to the H-E group. Moreover, no study participants were taken off the intake of LAC during OIT. In the H-E group, OVA-specific IgA₂ levels after OIT were significantly higher than before OIT. The ratios of OM-specific IgG₄/OM-specific IgE and OM-specific IgA₂/OM-specific IgE in the H-E group after OIT were significantly higher than before OIT. Conclusion: Our findings suggest that low-dose OIT using LAC is an effective and safe treatment for patients with severe egg allergy.

The importance of reducing risk in peanut allergy: Current and future therapies

The prevalence of peanut allergy has steadily increased during the past 10 years, especially in children. A 2009 to 2010 survey of more than 40,000 children (aged 0–17 years) in the United States found that peanut allergy was the most common food allergy, affecting 2% (1.5 million) of children nationwide. [1] Gupta R.S. Springston E.E. Warrier M.R. et al. The prevalence, severity, and distribution of childhood food allergy in the United States. Pediatrics. 2011; 128: e9-e17 Crossref PubMed Scopus (1024) Google Scholar Data from a 2014 meta-analysis of 29 studies from multiple European countries using various reporting methods estimated the occurrence of peanut allergy to be 0.3% (by positive food challenge result) to 4.1% (by peanut specific IgE positivity) in children aged 2 to 5 years and 0.4% (by self-reporting) to 9.8% (by peanut specific IgE positivity) in children aged 6 to 17 years. [2] Nwaru B.I. Hickstein L. Panesar S.S. Roberts G. Muraro A. Sheikh A. Prevalence of common food allergies in Europe: a systematic review and meta-analysis. Allergy. 2014; 69: 992-1007 Crossref PubMed Scopus (615) Google Scholar Is the better part of valor truly discretion?Annals of Allergy, Asthma & ImmunologyVol. 120Issue 2PreviewPeanut allergy affects 1.4% to 4.5% of children, depending on the study and methodology. Self-reported estimates have shown an alarming 3-fold increase in US populations over 10 years, whereas UK data from a longitudinal birth cohort with challenge-based evidence have not reflected such an alarming increase.1–4 Unfortunately, for years, the common peanut allergy management paradigm was to strictly avoid any potential exposure (including trace amounts) and carry self-injectable epinephrine. Now, we find the field on the cusp of what could be 2 therapies approved by the US Food and Drug Administration (FDA) for the treatment of peanut allergy in children in late 2018 or early 2019 (a commercial low-dose oral immunotherapy [OIT] capsule and an epicutaneous patch). Full-Text PDF

Safety and Efficacy of Low-Dose Oral Immunotherapy for Hen’s Egg Allergy in Children

The ideal dose for safe and effective oral immunotherapy (OIT) is unknown. The goal of this study was to investigate the efficacy and safety of low-dose OIT with approximately 1/32 of the volume of a whole egg.Thirty-three children (aged ≥5 years) with egg allergies confirmed by oral food challenge (OFC) against 1/32 of a heated whole egg (194 mg of egg protein) were enrolled. Twenty-one children were enrolled in the OIT group and 12 in the control group.Children in the OIT group were admitted to the hospital for 5 days of buildup, and then at home, this group was encouraged to consume 62 to 194 mg of egg protein in scrambled form once a day. The amount of egg eaten, severity of provoked symptoms, and treatments administered were recorded in a diary. Egg consumption was completely absent in the control group. Twelve months later, the daily intake of egg ceased for 2 weeks, and an open OFC was performed on up to one-half of a whole egg. There were no significant differences between the groups in terms of subject background.The proportion of subjects showing sustained unresponsiveness to 1/32 of a whole egg was 71.4% (15 of 21) in the OIT group and 0% (0 of 12) in the control group (P <.001). Subjects exhibiting sustained unresponsiveness to one-half of a whole egg were 33.3% (7 of 21) and 0% (0 of 12) in the OIT and control groups, respectively (P = .032). Compared with baseline levels, egg white– and ovomucoid-specific allergic markers were significantly different in the OIT group but not the control group. Adverse allergic reactions were infrequent, and most symptoms were classified as Grade 1 (mild). There were no Grade 3 (severe) symptoms reported. No subjects withdrew from the study, no epinephrine was used, and no emergency department visits occurred.This study demonstrates that low-dose egg OIT may be safe and effective in a high-risk egg-allergic population, inducing both immunologic changes and sustained unresponsiveness to low doses and higher doses of egg. In addition, most adverse reactions were mild, no severe symptoms were reported, no epinephrine was used, and there were no emergency department visits.One of the major concerns with traditional OIT to foods is the amount, frequency, and severity of adverse allergic reactions, often causing significant subject withdrawal from these studies. This study demonstrates that using a lower dose of OIT is potentially safer. It also demonstrated effectiveness at inducing sustained unresponsiveness to both a low dose and a higher dose of egg protein. There are several limitations to the study, the first being this was a nonrandomized, open-labeled trial with a small sample size. Also, sustained unresponsiveness was only measured 2 weeks after stopping therapy, whereas most traditional studies use 4 or 6 weeks. Nevertheless, this could prompt future randomized controlled trials examining the safety and effectiveness of low-dose OIT.

Safety and Efficacy of Low-Dose Oral Immunotherapy for Hen's Egg Allergy in Children

Background: The minimal dose for oral immunotherapy (OIT) tolerance is unknown. We investigated the efficacy and safety of low-dose OIT with 1/32 of the volume of a whole egg. Methods: Thirty-three children (aged ≥5 years) with egg allergies confirmed by oral food challenge against 1/32 of a heated whole egg (194 mg of egg protein) were enrolled. The OIT group ingested a scrambled egg once a day. The volume was gradually increased up to a maximum of 1/32 of a heated whole egg. Egg consumption was completely absent in the control group. Results: There were no significant differences in background between the OIT and control groups. Respectively, 71% (15/21) and 0% (0/12) of the patients in the OIT and control groups exhibited sustained unresponsiveness to 1/32 of a whole egg 2 weeks after stopping OIT after 12 months (p < 0.001); 33% (7/21) and 0% (0/12; p = 0.032), respectively, showed sustained unresponsiveness to 1/2 of a whole egg. Egg white- or ovomucoid-specific IgE levels in the OIT group were significantly lower than at baseline after 12 months. Egg white- or ovomucoid-specific IgG as well as IgG4 levels in the OIT group were significantly higher than baseline levels after 1, 3, 6, and 12 months. Adverse allergic reactions were rare, and most symptoms were mild. Conclusions: Low-dose OIT induced sustained unresponsiveness to 1/32 and 1/2 of a whole egg, with no severe symptoms. To improve food allergies, continuous intake of small amounts of these foods may be as effective as the consumption of larger quantities.

Low-Dose Oral Immunotherapy As an Early Intervention Strategy for Peanut Allergy

Low-Dose Oral Immunotherapy As an Early Intervention Strategy for Peanut Allergy

Inhibition of Allergen-Induced Airway Inflammation by Low-Dose Oral Immunotherapy with Transgenic Rice Seeds Independently of Immunoglobulin E Synthesis

Background: Oral immunotherapy is potentially useful for the treatment of allergic diseases. We previously demonstrated that allergen-induced airway inflammation and immunoglobulin E (IgE) production in mice were suppressed by oral administration of high-dose transgenic (Tg) rice seeds (approximately 50 g/kg/day) expressing a T cell epitope of Dermatophagoides pteronyssinus group 1 allergen (Der p 1). However, this amount of Tg rice seeds was not realistic in our daily life. In this study, allergen-induced airway inflammation and IgE production following oral immunotherapy with a realistic (lowest) dose of Tg rice seeds were investigated. Methods: Mice orally administered with Tg or non-Tg rice seeds at approximately 5 g/kg/day for 1 week were immunized with recombinant Der p 1, and then challenged with the corresponding allergen. The infiltration of inflammatory cells into the airways and the levels of allergen-specific serum IgE were examined. Results: Low-dose oral administration of Tg rice seeds significantly inhibited the allergen-induced infiltration of eosinophils and lymphocytes into the airways, but allergen-specific IgE synthesis was not changed. Conclusions: Low-dose oral immunotherapy with Tg rice seeds could suppress allergen-induced airway inflammation through mechanisms other than the downregulation of IgE synthesis.