Oral Immunotherapy Protocol Research Articles

A rare presentation of mammalian milk anaphylaxis in adults

Cow’s milk (CM) allergy is the most prevalent food allergy in children but is very rare in adults. We describe an unusual case of a patient who became allergic to CM and other mammalian milks, during her adult life, with anaphylaxis, and whom successfully underwent a CM oral immunotherapy (OIT). A 43 years-old women was referred to our Immunoallergy department in 2018 with a history of several anaphylactic episodes since 2011. All episodes are characterized by pruritus, generalized erythema and angioedema, and dyspnea. The first reaction occurred immediately after eating cheese with goat (GM) and sheep milks (SM). Since then, she started to evict every sort of milk/derivates. Four years later, she had a reaction after a corticosteroid administration with traces of CM. In 2017, she had another reaction immediately after eating a salad contaminated by cheese. She has a past history of asthma and rhinosinusitis with nasal polyps, but she had never been allergic to any food. In 2005, during her son breastfeeding (9 months), she underwent a rigorous eviction of CM/derivates because of his atopic dermatitis. Between 2006-2011 she reported several episodes of oropharyngeal tightening after eating foods containing CM. Skin-prick tests (Roxall®) to CM and proteins extracts were positive to casein-4x4mm, α-lactoalbumin-5x6mm and β-lactoglobulin-3x4mm. Prick by prick tests were positive to CM-7x7mm, GM-5x6mm and SM-5x5mm. Specific IgEs (UniCAP,ThermoFisher®) were found to GM-0,36 kU/l, SM-0,29 kU/l, CM-0,55 kU/l, casein-6,48 kU/l, α-lactoalbumin-0,34 kU/l and β-lactoglobulin-0,04 kU/l. She was successfully submitted to a CM-OIT protocol, reaching a daily dose of 200ml in 4 months (7 sessions). She had several mild adverse reactions, all with spontaneous resolution. Currently, she completed 6 months of the maintenance phase, with a free diet for CM, and a significant improvement in her quality of life. It was proposed an OIT for GM or SM but she refused for the moment. To our knowledge, this is the first case report of a patient who became sensitized to CM proteins in adult life who successfully underwent a CM OIT protocol. The patterns of allergy are changing, with the appearance, in adulthood, of severe food allergies characteristically associated with childhood. CM-OIT is a safe and effective treatment for severe and long-lasting CM allergy. The protocol used allowed to achieve tolerance within a short period of time. Maintenance of 200 mL daily ingestion enables a diet without restrictions, with a clear positive impact on the quality of life.

Oral Immunotherapy with Cow's Milk Allergy: Five Years' Experience from a Single Center in Turkey

Background:Oral immunotherapy for cow’s milk allergy is an effective treatment option because of its ability to increase the threshold for clinical reactions.Aims:To present our experience of oral immunotherapy for cow’s milk allergy in the pediatric allergy outpatient clinic, and to evaluate the long-term efficacy of oral immunotherapy and risk factors for adverse reactions during oral immunotherapy.Study Design:Single-center retrospective cohort study.Methods:Forty-two patients with Immunoglobulin-E-mediated cow’s milk allergy who complied with the oral immunotherapy protocol were evaluated in this study. The treatment consisted of a rapid escalation phase with an oral food challenge step that included milk doses. During the build-up phase, increasing quantities of cow’s milk were administered until the patient was able to consume 200 mL of cow’s milk daily.Results:The mean age of starting the oral immunotherapy was 40.2±3.2 (range, 36-156) months, and 54.8% (n=23) of the patients were males. The mean duration of the build-up phase was 18.1±5.6 (range, 9-41) weeks, and the mean maintenance phase was 29.1±11.6 (range, 12-63) months. During the oral immunotherapy, 36 adverse reactions (78% mild and 22% moderate) occurred in 16 (38%) patients. There were no differences in the age of starting the oral immunotherapy (p=0.19), cow’s milk-specific Immunoglobulin-E levels (p=0.17), and cumulative provocative doses of oral food challenges (p=0.78) between the two groups of patients with and without adverse reactions. The wheal diameters to cow’s milk were higher in the group with adverse reactions (p=0.03). There was no difference in the oral immunotherapy onset age between patients with and without a history of anaphylaxis (p=0.38). The patients with a history of anaphylaxis had more adverse reactions (p=0.04) and a higher number of reactions during the oral immunotherapy (p=0.01), and a higher mean duration of the up-dosing phase (p=0.04) compared with patients without anaphylaxis.Conclusion:Oral immunotherapy is a treatment option in patients with cow’s milk allergy because of its high efficacy. Adverse reactions occur in about 40% of cases and are mostly mild. It should be administered with caution to patients with a history of anaphylaxis and a higher wheal diameter to cow’s milk in the skin prick test.

Feasibility of a 3-step protocol of wheat oral immunotherapy in children with severe wheat allergy.

BackgroundWheat allergy is not an uncommon event among Thai children. Despite strict avoidance, some patients developed reactions after accidental exposure to minute amount of wheat and thus disturbed their quality of life. Wheat oral immunotherapy (OIT) has been reported to be an alternative treatment for such patients.ObjectiveWe designed a new 3-step wheat OIT protocol for treatment of severe wheat allergy in Thai patients. The feasibility of the protocol is evaluated and is reported here in this paper.MethodsWe retrospectively reviewed medical records of 26 patients who had undergone wheat OIT during a 30-month period. The 3-step protocol consisted of an initial phase of double-blind, placebo-controlled food challenge (DBPCFC) and initiation of OIT, a build-up phase, and a maintenance phase. Patient retention in the protocol was the main outcome for this feasibility study. Adverse effects during OIT were recorded. Correlation between serum specific IgE (SpIgE) to wheat and eliciting dose in phase I was determined.ResultsFourteen females and 12 males with a median age of 6 years were studied. Their median age when wheat allergy began was 8 months. Median SpIgE to wheat was high (198 kUA/L). All patients developed reactions during DBPCFC with 17 of 26 patients had moderate to severe reactions required adrenaline injections. Median of eliciting dose of wheat was exceedingly low, i.e., 20 mg of wheat protein. At the end of the study, 23 of 26 patients (88%) were still in the study. Adverse reactions during the build-up phase was frequent (13 patients, 50%), with adrenaline required in 6 occasions. Six patients reached maintenance phase.ConclusionThe new 3-step wheat OIT protocol was feasible in these highly wheat-sensitized patients. Despite a high retention rate, a high rate of adverse effects was observed both during DBPCFC and build-up phases.

A 5-year summary of real-life dietary egg consumption after completion of a 4-year egg powder oral immunotherapy (eOIT) protocol

The majority of children with sustained unresponsiveness after extended egg OIT are able to successfully introduce dietary egg. OIT outcome may be predictive of frequency, type (concentrated, baked), and quantity of egg ingested in the long term.

Oral Immunotherapy for Peanut Allergy (PACE): A Systematic Review and Meta–analysis of Efficacy and Safety

To systematically review the efficacy and safety of peanut oral immunotherapy (OIT) compared with allergen avoidance or placebo OIT for peanut allergy.The population included individuals with peanut allergy (61% male, 39% female), the majority of whom were children (median age: 8.7 years; interquartile range [IQR]: 5.9–11.2 years) participating in peanut OIT trials in North America, Australia, and Western Europe.This systematic review and meta-analysis included a comprehensive search of international health care databases from the United States, Latin America, Europe, and China through December 2018. Authors performed searches for randomized controlled trials comparing peanut OIT to no OIT for the treatment of peanut allergy. The authors screened studies, extracted data, assessed risk of bias, and assessed quality of evidence by the Grading of Recommendations Assessment, Development, and Evaluation approach. The main outcomes included treatment efficacy (ie, proportion of patients passing an oral food challenge), anaphylaxis, allergic or adverse reactions, epinephrine use, and quality of life.Twelve randomized controlled trials were included, with 1041 participants in total undergoing peanut OIT for a median follow-up of 1.0 year (IQR: 0.8–1.4), achieving a median target dose of 2000 mg of peanut protein (IQR: 375–4000). Passing a supervised, in-clinic oral food challenge was more likely in the OIT group. Subjects undergoing peanut OIT had increased anaphylaxis risk (risk ratio: 3.12 [95% confidence interval (CI): 1.76–5.55]), anaphylaxis frequency (incidence rate ratio: 2.72 [95% CI: 1.57–4.72]), and epinephrine use (risk ratio: 2.21 [95% CI: 1.27–3.83]). Peanut OIT increased serious adverse events and nonanaphylactic reactions. These findings were irrespective of OIT protocol, proprietary formulation or not, and phase of OIT (build-up versus maintenance). Quality of life was not different between groups.High-quality evidence shows that current peanut OIT regimens effectively achieve a modest level of desensitization but clinically result in a net increase in anaphylaxis and other allergic reactions compared with avoidance or placebo, rather than preventing them, as intended. These data support the need for improved food allergy treatment approaches with an enhanced safety profile.Hesitancy to implement OIT in routine clinical practice centers around concerns for safety, standardization of approach, practicality of long-term therapy maintenance, and identification of patients who will respond best with the fewest side effects. Although most adverse effects from OIT are mild and do not prevent patients from continuing therapy, the potential for life-threatening anaphylaxis exists. Despite the safety concerns outlined in this report, OIT is being offered in some clinical practices and is expected be available on a larger scale in the near future. It is important to remember that OIT may not be the best fit for many food-allergic patients, and as we near the likely acceptance of a US Food and Drug Administration–approved peanut OIT product, patients will seek advice from their pediatrician before talking to an allergist to help them navigate the pros and cons of interventional therapy versus the traditional approach of maintaining strict allergen avoidance. Salient points for the pediatrician to remember include the following. (1) OIT and all other products currently under investigation for treatment of food allergy provide benefit while on therapy but do not appear to induce sustained remission for the majority of allergic patients. (2) There are no surrogate biomarkers to identify which patients will receive the greatest benefit with the fewest side effects. (3) Anaphylaxis while on therapy is a potential side effect, and patients must continue to carry autoinjectable epinephrine at all times. Shared decision-making and an open and honest discussion with families considering therapeutic options are necessary in providing comprehensive care of our patients with food allergy and their families.

Effectiveness Of Clinician Dose Blinding In An Oral Immunotherapy Protocol

Effectiveness Of Clinician Dose Blinding In An Oral Immunotherapy Protocol

High- and low-dose oral immunotherapy similarly suppress pro-allergic cytokines and basophil activation in young children.

Mechanisms underlying oral immunotherapy (OIT) are unclear and the effects on immune cells at varying maintenance doses are unknown. We aimed to determine the immunologic changes caused by peanut OIT in preschool aged children and determine the effect on these immune responses in groups ingesting low or high-dose peanut OIT (300mg or 3000mg, respectively) as maintenance therapy. Blood was drawn at several time-points throughout the OIT protocol and PBMCs isolated and cultured with peanut antigens. Secreted cytokines were quantified via multiplex assay, whereas Treg and peanut-responsive CD4 T cells were studied with flow cytometry. Basophil activation assays were also conducted. Th2-, Th1-, Th9- and Tr1-type cytokines decreased over the course of OIT in groups on high- and low-dose OIT. There were no significant differences detected in cytokine changes between the high- and low-dose groups. The initial increase in both the number of peanut-responsive CD4 T cells and the number of Tregs was transient and no significant differences were found between groups. Basophil activation following peanut stimulation was decreased over the course of OIT and associated with increased peanut-IgG4/IgE ratios. No differences were found between high- and low-dose groups in basophil activation at the time of desensitization or sustained unresponsiveness oral food challenges. Peanut OIT leads to decreases in pro-allergic cytokines, including IL-5, IL-13, and IL-9 and decreased basophil activation. No differences in T cell or basophil responses were found between subjects on low or high-dose maintenance OIT, which has implications for clinical dosing strategies.

Oral and sublingual immunotherapy for egg allergy.

Clinical egg allergy is a common food allergy. Current management relies upon strict allergen avoidance. Oral immunotherapy might be an optional treatment, through desensitization to egg allergen. To determine the efficacy and safety of oral and sublingual immunotherapy in children and adults with immunoglobulin E (IgE)-mediated egg allergy as compared to a placebo treatment or an avoidance strategy. We searched 13 databases for journal articles, conference proceedings, theses and trials registers using a combination of subject headings and text words (last search 31 March 2017). We included randomized controlled trials (RCTs) comparing oral immunotherapy or sublingual immunotherapy administered by any protocol with placebo or an elimination diet. Participants were children or adults with clinical egg allergy. We retrieved 97 studies from the electronic searches. We selected studies, extracted data and assessed the methodological quality. We attempted to contact the study investigators to obtain the unpublished data, wherever possible. We used the I² statistic to assess statistical heterogeneity. We estimated a pooled risk ratio (RR) with 95% confidence interval (CI) for each outcome using a Mantel-Haenzel fixed-effect model if statistical heterogeneity was low (I² value less than 50%). We rated the quality of evidence for all outcomes using GRADE. We included 10 RCTs that met our inclusion criteria, that involved a total of 439 children (oral immunotherapy 249; control intervention 190), aged 1 year to 18 years. Each study used a different oral immunotherapy protocol; none used sublingual immunotherapy. Three studies used placebo and seven used an egg avoidance diet as the control. Primary outcomes were: an increased amount of egg that can be ingested and tolerated without adverse events while receiving allergen-specific oral immunotherapy or sublingual immunotherapy, compared to control; and a complete recovery from egg allergy after completion of oral immunotherapy or sublingual immunotherapy, compared to control. Most children (82%) in the oral immunotherapy group could ingest a partial serving of egg (1 g to 7.5 g) compared to 10% of control group children (RR 7.48, 95% CI 4.91 to 11.38; RD 0.73, 95% CI 0.67 to 0.80). Fewer than half (45%) of children receiving oral immunotherapy were able to tolerate a full serving of egg compared to 10% of the control group (RR 4.25, 95% CI 2.77 to 6.53; RD 0.35, 95% CI 0.28 to 0.43). All 10 trials reported numbers of children with serious adverse events (SAEs) and numbers of children with mild-to-severe adverse events. SAEs requiring epinephrine/adrenaline presented in 21/249 (8.4%) of children in the oral immunotherapy group, and none in the control group. Mild-to-severe adverse events were frequent; 75% of children presented mild-to-severe adverse events during oral immunotherapy treatment versus 6.8% of the control group (RR 8.35, 95% CI 5.31 to 13.12). Of note, seven studies used an egg avoidance diet as the control. Adverse events occurred in 4.2% of children, which may relate to accidental ingestion of egg-containing food. Three studies used a placebo control with adverse events present in 2.6% of children. Overall, there was inconsistent methodological rigour in the trials. All studies enrolled small numbers of children and used different methods to provide oral immunotherapy. Eight included studies were judged to be at high risk of bias in at least one domain. Furthermore, the quality of evidence was judged to be low due to small numbers of participants and events, and possible biases. Frequent and increasing exposure to egg over one to two years in people who are allergic to egg builds tolerance, with almost everyone becoming more tolerant compared with a minority in the control group and almost half of people being totally tolerant of egg by the end of treatment compared with 1 in 10 people who avoid egg. However, nearly all who received treatment experienced adverse events, mainly allergy-related. We found that 1 in 12 children had serious allergic reactions requiring adrenaline, and some people gave up oral immunotherapy. It appears that oral immunotherapy for egg allergy is effective, but confidence in the trade-off between benefits and harms is low; because there was a small number of trials with few participants, and methodological problems with some trials.

Observational long-term follow-up study of rapid food oral immunotherapy with omalizumab

BackgroundA number of clinical studies focused on treating a single food allergy through oral immunotherapy (OIT) with adjunctive omalizumab treatment have been published. We previously demonstrated safety and tolerability of a rapid OIT protocol using omalizumab in a phase 1 study to achieve desensitization to multiple (up to 5) food allergens in parallel, rapidly (7–36 weeks; median = 18 weeks). In the current long-term, observational study, we followed 34 food allergic participants for over 5 years, who had originally undergone the phase 1 rapid OIT protocol.MethodsAfter reaching the maintenance dose of 2 g protein for each of their respective food allergens as a part of the phase 1 study, the long-term maintenance dose was reduced for some participants based on a pragmatic team-based decision. Participants were followed up to 62 months through standard oral food challenges (OFCs), skin prick tests, and blood tests.ResultsEach participant passed the 2 g OFC to each of their offending food allergens (up to 5 food allergens in total) at the end of the long-term follow-up (LTFU) study.ConclusionOur data demonstrate the feasibility of long-term maintenance dosing of a food allergen without compromising the desensitized status conferred through rapid-OIT.Trial registration Registry: Clinicaltrials.gov. Registration numbers: NCT01510626 (original study), NCT03234764 (LTFU study). Date of registration: November 29, 2011 (original study); July 26, 2017 (LTFU study, retrospectively registered)

Changes in biomarkers during a six-month oral immunotherapy intervention for cow's milk allergy.

Oral immunotherapy (OIT) is a promising but still experimental method to treat children with cow's milk (CM) allergy (CMA). We evaluated changes in allergic, immunological and inflammatory parameters, which happened during the six-month OIT for CMA. We treated 28 school-aged children with CMA using OIT with a double-blind placebo-controlled design. After the controlled study finished, the placebo group was treated with the same but open-label OIT protocol. Sixteen immune variables were tested before and after the six-month OIT. Before OIT, the median serum CM-specific immunoglobulin (Ig) E was 18.0kIU/L in the intervention group and 9.4kIU/L in the placebo group (p=0.46). At six months, interleukin (IL)-6 and IL-10 were significantly higher in the intervention group. When the changes during the blinded and open OIT were analysed together for both groups, blood eosinophils and serum total IgE decreased and milk-specific IgG and IgG4, serum IL-4 and IL-6, and serum leptin and resistin increased significantly. Preliminary evidence was found that markers of allergy such as blood eosinophils and serum IgE decreased and milk-specific IgG and IgG4 increased during OIT. Adipokines, leptin and resistin, which functionally are cytokines linked to Th1-type response, increased during OIT.

Oral Food Desensitization in Children With IgE-Mediated Cow's Milk Allergy: Immunological Changes Underlying Desensitization.

PurposeThis study aimed to evaluate the safety and efficacy to induce clinical desensitization to cow's milk (CM) of an oral immunotherapy (OIT) protocol in a pediatric population with cow's milk allergy (CMA). In addition, the immune responses against β-casein, of peripheral blood mononuclear cells (PBMCs) from CMA patients, before and after the protocol were evaluated and compared to a nonallergic population.MethodsA group of 20 children with IgE-mediated CMA and 15 nonallergic children were recruited. Allergic subjects underwent an OIT protocol based on weekly doses of commercial semi-skimmed ultra-high temperature treated (UHT) CM, followed by a maintenance phase. Immune profiles and changes in all subjects were investigated by measuring Th1, Th2, and Treg cytokines, transcription factors, and specific IgE and IgG4 levels.ResultsThe CM-OIT protocol enabled to desensitize 70% of the allergic patients. Successful OIT was accompanied by significant increases in casein-specific IgG4 levels, together with a reduction in the concentration of antigen-specific IgE and in IL-5, IL-13, and IL-10 production by β-casein-stimulated PBMCs. Baseline significant differences observed between allergic and nonallergic children in IL-13 and IL-5 levels were no longer found once the protocol had finished.ConclusionsThe OIT protocol was safe and effective in inducing milk desensitization in 70% of the children with CMA, leading to alterations in their immune profiles toward a nonallergic phenotype.

The Use of Omalizumab in Food Oral Immunotherapy

Food allergy is an important health issue that affects up to 8% of the population. The management of allergic patients involves allergen avoidance and prompts the treatment of accidental reactions, as no curative treatment is available so far in routine practice. Oral immunotherapy (OIT) is a promising therapeutic alternative, but it is associated with frequent allergic reactions and cost-effectiveness issues. In hopes of reducing such reactions, a number of trials have used omalizumab, an anti-IgE monoclonal humanized antibody, as adjunctive therapy in OIT. The allergens studied in these omalizumab-enabled OIT trials include peanuts, milk, eggs, or mixes of multiple foods. In this article, we review the major findings from these studies and discuss potential benefits and issues related to omalizumab-enabled OIT. Results from the previous trials suggest that the use of omalizumab could potentially lead to safer and more efficient OIT protocols, by reducing the number and severity of reactions, and increasing allergen tolerance threshold. While more evidence is needed with regard to the maintenance of the long-term tolerance after OIT, omalizumab's potential immunomodulatory role could be of benefit. More studies are needed to further document this new indication for omalizumab.

Two-weeks-sustained unresponsiveness by oral immunotherapy using microwave heated cow's milk for children with cow's milk allergy.

BackgroundSeveral studies have reported that oral immunotherapy (OIT) is effective for children with cow’s milk (CM) allergy. These studies reported the efficacy of OIT in terms of desensitization, but did not describe sustained unresponsiveness to CM. The aim of this study was to evaluate the efficacy of the OIT protocol using microwave heated cow’s milk (MH-CM) in terms of 2-weeks-sustained unresponsiveness (2-weeks-SU) and safety.MethodsForty-eight children were enrolled in this study. Thirty-one children agreed to receive rush OIT using MH-CM (the OIT group) and another 17 children who did not want to receive rush OIT formed the untreated group. Rates of desensitization and 2-weeks-sustained unresponsiveness were compared between the two groups at 1 year after the start of OIT. We followed up these rates and safety data for another year and for longer in the OIT group.ResultsNo children in the untreated group did not pass an open food challenge to CM. Of the 31 children in the OIT group, 14 (P = 0.002) achieved desensitization, and 8 (P = 0.036) achieved 2-weeks-SU to CM at 1 year from the start of OIT. Two years after the start of OIT, both the rate of desensitization and the rate of 2-weeks-SU in the OIT group significantly increased compared with the rates at 1 year (P = 0.025 and P = 0.008 respectively).ConclusionsThe rush OIT protocol using MH-CM was effective at inducing 2-weeks-SU s to CM and had a good safety profile in children with CM allergy.Trial registration Approval number: 324, Registered 3 February 2009

Efficacy of baked milk oral immunotherapy in baked milk–reactive allergic patients

Patients with IgE-mediated cow's milk allergy who are nonreactive to baked milk (BM) can be desensitized with BM to promote tolerance to unheated milk (UM). We sought to test whether patients who are BM reactive can progress in BM oral immunotherapy (OIT) and become desensitized to UM as well. Fifteen patients (>4 years) who previously failed to complete our milk OIT program were enrolled into the BM OIT protocol. A dose of BM (180 °C for 30 minutes) which was less than the eliciting dose was increased 50% monthly while under medical supervision until the primary outcome dose of 1.3 g/d BM protein was achieved. Basophil reactivity and milk protein-specific IgE binding were analyzed at the first round of BM OIT therapy (T0) and at 12 months of BM treatment. In terms of the primary outcome, only 3 (21%) of 14 patients tolerated the 1.3 g/d BM dose. Although some patients initially progressed in BM OIT, 8 of 11 failed because of IgE-mediated reactions. Three did not complete the program because of non-IgE-mediated factors. An increase in challenge threshold to UM was noted in patients continuing until 12 months (P = .003), including those among whom reactions precluded continuation in the program. Patients (n = 3) who successfully reached maintenance had decreased milk-specific IgE reactivity. Furthermore, the mean difference at T0 between induced HM and UM percentages of CD203c expression was significantly lower in patients who successfully completed BM OIT than in those who did not (-11% vs 4.4%, P = .0002), which is consistent with their decreased clinical reactivity to BM. Although use of hypoallergenic BM in OIT is a promising therapy, care must be taken before its administration in BM-reactive patients because of the risk for anaphylaxis and only limited increase in challenge threshold attained.

Clinical efficacy and immunological changes subjacent to egg oral immunotherapy

BackgroundEvidence of the efficacy of food oral immunotherapy (OIT) is not robust enough to change clinical practice from current standard management. Furthermore, the immunologic changes underlying food desensitization are unknown. ObjectiveTo establish the immunologic basal status and differences between an egg-allergic group of children and a population of nonallergic children and to investigate the safety and efficacy of a specific egg OIT protocol to induce clinical desensitization and the associated immune responses. MethodsChildren with or without egg allergy were recruited. Allergic subjects underwent an OIT protocol based on weekly doses of egg protein and a maintenance phase. Immune profile and changes in all subjects were investigated by measuring T-helper cells types 1 and 2 (TH1 and TH2) and T-regulatory cytokines and transcription factors and egg-specific IgE and IgG4 levels. ResultsAt baseline, a significantly lower production of ovalbumin-specific interleukin (IL)-10 and tumor necrosis factor-α and a trend toward higher IL-5 and IL-13 were found in allergic children. The egg OIT protocol enabled 60% of them to ingest 32 mL of egg white. Significant increases in egg-specific IgG4 levels and IL-10 production, with a trend toward lower IL-5 and IL-13 and higher tumor necrosis factor-α and interferon-γ levels, and significant decreases in egg-specific IgE concentration were observed. ConclusionEgg-allergic individuals display a bias toward TH2 type cytokine production and decreased TH1 and IL-10 responses compared with nonallergic individuals. The OIT protocol was safe and effective in inducing egg desensitization, leading to a shift in the immune profile of allergic individuals toward a nonallergic phenotype.

Peanut oral immunotherapy in adolescents: study protocol for a randomized controlled trial.

BackgroundPeanut allergy is an increasingly common health problem. Current treatment guidelines are based on strict avoidance. However, in the last few years, oral immunotherapy protocols have shown promising results yielding increased tolerance to peanut in allergic children. Adolescence is particularly at risk.Methods/DesignWe have designed a randomized, double-blind, placebo-controlled, multicenter study to investigate the efficacy and safety of peanut oral escalating immunotherapy in a 12- to 18–year-old population with proved allergy to peanut. Patients are selected when the threshold of peanut intake is over 100 mg and 2 cumulated g on the first double-blind, placebo-controlled oral food challenge (DBPCOFC).During the build-up placebo-controlled blinded phase, doses containing peanut or placebo will be administered by gradual up-dosing from 10 mg to 2 g with 2-weekly increments. After this first randomized phase, the desensitized participants will continue to intake native peanut in an unblinded process during 13 or 37 weeks following a second randomization. Adverse events are picked up and managed throughout the entire protocol.The main endpoint is the percentage of patients with negative DBPCOFC at the threshold of 2 g of cumulative peanut at the end of the build-up phase of 24 weeks.Secondary endpoints include: (1) desensitization 6 weeks and 6 months after the end of the maintenance phase; (2) adverse effects during the build-up phase; (3) immunological profile confirming peanut desensitization. Immunologic assays will be carried out at every DBPCOFC and at the middle of the build-up phase to evaluate the peanut immunologic profile modifications.DiscussionThis double-blind, placebo-controlled study will be, to our knowledge, the first evaluation of a peanut oral immunotherapy protocol in teenagers in the purpose to reduce severe reactions after unexpected intake and to improve quality of life.Trial registrationClinicalTrial.gov: NCT02046083 (23 January 2014).

Immunologic changes underlying to an egg OIT protocol in a pediatric population

Background Egg allergy is one of the most common food allergies in childhood with an estimated prevalence of 2.6 %. Oral immunotherapy (OIT) appears as a promising approach to induce egg-tolerance. However, the immune mechanisms underlying this treatment are not completely known. The purpose of the study was to compare the immune responses against egg allergens of a pediatric population under an OIT protocol before and after the protocol was finished.

Modified peanut oral immunotherapy protocol safely and effectively induces desensitization

Modified peanut oral immunotherapy protocol safely and effectively induces desensitization

Oral and sublingual immunotherapy for egg allergy.

Clinical egg allergy is a common food allergy. Current management relies upon strict allergen avoidance. Oral immunotherapy (OIT) might be an optional treatment, through desensitization to egg allergen. We aimed to assess the successful desensitization and development of tolerance to egg protein and the safety of egg oral and sublingual immunotherapy in children and adults with immunoglobulin E (IgE)-mediated egg allergy as compared to a placebo treatment or an avoidance strategy. We searched 13 databases for journal articles, conference proceedings, theses and unpublished trials using a combination of subject headings and text words (the last search was on 5 December 2013). Randomized controlled trials (RCTs) were included. All age groups with clinical egg allergy were to be included. We retrieved 83 studies from the electronic searches. We selected studies, extracted data and assessed the methodological quality. We attempted to contact the study investigators to obtain the unpublished data, wherever possible. We used the I² statistic to assess statistical heterogeneity. We estimated a pooled risk ratio (RR) with 95% confidence interval (CI) for each outcome using a Mantel-Haenzel fixed-effect model if statistical heterogeneity was low (I² value less than 50%). We included four RCTs with a total of 167 recruited individuals (OIT 100; control 67 participants), all of whom were children (aged four to 15 years). One study used a placebo and three studies used an avoidance diet as the control. Each study used a different OIT protocol. Thirty nine per cent of OIT participants were able to tolerate a full serving of egg compared to 11.9% of the controls (RR 3.39, 95% CI 1.74 to 6.62). Forty per cent of OIT participants could ingest a partial serving of egg (1 g to 7.5 g; RR 5.73, 95% CI 3.13 to 10.50). Sixty nine per cent of the participants presented with mild-to-severe adverse effects (AEs) during OIT (RR 6.06, 95% CI 3.11 to 11.83). Five of the 100 participants receiving OIT required epinephrine. We cannot comment on whether over- or under-reporting of AEs was a concern based on the available data. Overall there was inconsistent methodological rigour in the trials. The studies were small and the quality of evidence was low. Current evidence suggests that OIT can desensitize a large number of egg-allergic patients, although it remains unknown whether long-term tolerance develops. A major difficulty of OIT is the frequency of AEs, though these are usually mild and self-limiting. The use of epinephrine while on OIT seems infrequent. There are no standardized protocols for OIT and guidelines would be required prior to incorporating desensitization into clinical practice.

Phase 1 results of safety and tolerability in a rush oral immunotherapy protocol to multiple foods using Omalizumab

BackgroundUp to 30% of patients with food allergies have clinical reactivity to more than one food allergen. Although there is currently no cure, oral immunotherapy (OIT) is under investigation. Pilot data have shown that omalizumab may hasten the ability to tolerate over 4 g of food allergen protein.ObjectiveTo evaluate the safety and dose tolerability of a Phase 1 Single Site OIT protocol using omalizumab to allow for a faster and safe desensitization to multiple foods simultaneously.MethodsParticipants with multiple food allergies received OIT for up to 5 allergens simultaneously with omalizumab (rush mOIT). Omalizumab was administered for 8 weeks prior to and 8 weeks following the initiation of a rush mOIT schedule. Home reactions were recorded with diaries.ResultsTwenty-five (25) participants were enrolled in the protocol (median age 7 years). For each included food, participants had failed an initial double-blind placebo-controlled food challenge at a protein dose of 100 mg or less. After pre-treatment with omalizumab, 19 participants tolerated all 6 steps of the initial escalation day (up to 1250 mg of combined food proteins), requiring minimal or no rescue therapy. The remaining 6 were started on their highest tolerated dose as their initial daily home doses. Participants reported 401 reactions per 7,530 home doses (5.3%) with a median of 3.2 reactions per 100 doses. Ninety-four percent (94%) of reactions were mild. There was one severe reaction. Participants reached their maintenance dose of 4,000 mg protein per allergen at a median of 18 weeks.ConclusionThese phase 1 data demonstrate that rush OIT to multiple foods with 16 weeks of treatment with omalizumab could allow for a fast desensitization in subjects with multiple food allergies. Phase 2 randomized controlled trials are needed to better define safety and efficacy parameters of multi OIT experimental treatments with and without omalizumab.