Efficacy Of Oral Immunotherapy Research Articles

Peanut oral immunotherapy using an extensively heated and baked novel composition of peanuts.

Oral immunotherapy (OIT) is an increasingly acceptable therapeutic option for peanut-allergic (PA) children, despite significant side effects. Major peanut allergenic proteins are heat-resistant and are not rendered hypoallergenic after baking or cooking. Lyophilized peanut protein-MH (LPP-MH) is a novel composition from developing peanuts, enabling cooking-induced reduction in allergenicity. We aimed to explore the safety and efficacy of OIT, with extensively heated and baked (EHEB) LPP-MH in PA children. In a single-arm, single-center, pilot study, PA children with a single highest tolerated dose of <100 mg peanut protein were placed on a 40-week OIT protocol with 300 mg daily of heat-treated LPP-MH. A repeat open peanut food challenge was performed after 40 weeks of treatment and at a 6-12 months of follow-up visit. Thirty-three children with PA were enrolled, with a mean cumulative tolerated dose (MCTD) of 71.2 mg PP (95% CI 45-100 mg). After 40 weeks, 32/33 patients were able to consume more than 300 mg of natural PP, with MCTD of 1709 mg (CI 365-3675 mg). There were no severe allergic reactions requiring epinephrine, during any of the observed LPP-MH challenges or any treatment related doses at home. After 6-12 months on daily maintenance, the MCTD was 8821 mg (95% CI 1930-13,500 mg). This enabled most children age-appropriate dietary inclusion of peanuts. An OIT protocol with heat-treated LPP-MH, a novel composition from developing peanuts, seems a potentially safe and efficacious OIT modality for PA children, enabling the introduction of dietary levels of peanut proteins in highly allergic PA children. Validation in randomized controlled studies is mandated.

Food Allergen Nitration Enhances Safety and Efficacy of Oral Immunotherapy in Food Allergy.

(1) Background: Posttranslational protein modifications have been demonstrated to change protein allergenicity. Previously, it was reported that pretreatment with highly nitrated food proteins induced a tolerogenic immune response in an experimental mouse model and in human immune cells. Here, we investigated a possible therapeutic effect of modified proteins and evaluated the safety of oral exposure to highly nitrated proteins in an experimental food allergy model. (2) Methods: BALB/c mice were orally sensitized towards ovalbumin (OVA) under gastric acid suppression. Thereafter, treatment via intragastric gavage with maximally nitrated OVA (nOVAmax) and OVA as a control was performed six times every 2 weeks. On the last day of experiments, all the treated mice were orally challenged with OVA. Systemic anaphylactic reaction was determined by measuring the core body temperature. Moreover, antibody levels, regulatory T cell numbers, cytokine levels and histology of antrum tissues were analyzed. (3) Results: After oral immunotherapy, OVA-specific IgE titers were decreased while IgG1 titers were significantly elevated in the mice receiving OVA. After oral challenge with OVA, nOVAmax-treated allergic animals showed no drop of the core body temperature, which was observed for OVA-allergic and OVA-treated allergic animals. Significantly fewer eosinophils and mast cells were found in the gastric mucosa of the allergic mice after nOVAmax treatment. (4) Conclusions: Oral immunotherapy with nOVAmax reduced allergic reactions upon allergen exposure and the number of allergen effector cells in the gastric mucosa. Thus, maximally nitrated allergens enabled an efficient and safe treatment for food allergy in our experimental model.

Weighing the benefits and risks of oral immunotherapy in clinical practice

Food allergies are common and affect 6-8% of children in the United States; they pose a significant burden on the quality of life of children with allergy and their caregivers due to multiple daily restrictions. Despite the recommended dietary avoidance, reactions tend to occur due to unintentional exposure to the allergenic food trigger. Fear of accidental ingestions with potentially severe reactions, including anaphylaxis and death, creates anxiety in individuals with food allergy. Oral immunotherapy has emerged as a form of active and potentially disease-modifying treatment for common food allergies encountered in childhood. The efficacy of oral immunotherapy is high, with the majority of participants achieving desensitization and, as a result, protection from trace exposures and improved quality of life. The main risk of oral immunotherapy consists of allergic reactions to treatment. In general, rates of allergic reactions and anaphylaxis are reported to be higher in individuals pursuing therapy options, but most subjects who undergo oral immunotherapy will likely experience mild or moderate reactions during treatment. Adverse events tend to reduce in both frequency and number in the maintenance period. The use of immune modulators alongside oral immunotherapy has been suggested, with the aim to improve efficacy and safety, and to facilitate the overall process. It is evident that the landscape of food allergy management is changing and that the future looks brighter, with different options emerging over time. The process of how to choose the appropriate option becomes a discussion between the clinician and the patient, which involves a joint review of the current medical evidence but also the patient's preference for balancing particular attributes of the treatment. By working together, providers and patients will ensure achievement of the best possible outcome for children with food allergies.

Food-Induced Anaphylaxis in Infants: Can New Evidence Assist with Implementation of Food Allergy Prevention and Treatment?

Previous guidance on infant anaphylaxis largely relied on data from older children and adults. Infants are a unique subgroup, which presents specific challenges because infants are unable to verbalize symptoms, although the magnitude of underrecognition is not well studied. Data show that strict avoidance of allergens is difficult to achieve in the infant age group and a source of stress and anxiety for their caregivers. Recent studies suggest that infant anaphylaxis is less severe than in older children, which could greatly assist with implementation of food allergy prevention and treatment. New evidence from clinical trials and observational and real-world studies show that infant anaphylaxis is rare on first ingestion of a new food and typically not severe when it occurs, which parents may not be aware of when preparing to introduce peanut or other common food allergens to infants for the purpose of prevention. The better safety and efficacy of oral immunotherapy in infants and preschoolers could help prevent undesired psychosocial consequences of longstanding food allergy such as anxiety, bullying, and poor quality of life. Evidence from recent years on the lower risk of infant anaphylaxis and its severity could move allergy practice toward the confidence that regular, long-term ingestion provides.

Long-term efficacy of oral immunotherapy for hen's egg, cow's milk, and wheat allergies in children

Long-term efficacy of oral immunotherapy for hen's egg, cow's milk, and wheat allergies in children

Advances in the management of peanut allergy (oral immunotherapy and epicutaneous immunotherapy).

Background: Peanut allergy affects up to 2% of the general population and carries not only the risk of potentially life-threatening allergic reactions but also negatively impacts day to day life for patients and their families. Advances in knowledge in immunotherapy is providing families with options for proactive treatment. Objective: To examine the available data for oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT) for peanut allergy. Methods: This review discusses recent studies that evaluated the safety and efficacy of OIT and EPIT to induce desensitization to peanut and identifies factors that should be considered when guiding families in treatment decisions. Results: Results of studies have demonstrated that immunotherapy can raise the threshold of peanut allergen to induce allergic reactions for many patients, thereby potentially reducing the risk for allergic reactions and decreasing the daily burden of peanut allergy. However, adverse reactions, which range from mild to severe, are possible with immunotherapy. Shared decision-making will be important to determine the best approach for peanut allergy management for each individual and his or her family. Conclusion: OIT and EPIT will offer patients and families more options for managing peanut allergies. Recent data from phase III studies on OIT and EPIT as well as real-world data on OIT advance the understanding of the efficacy and safety of these approaches. On-going studies aim to identify biomarkers to enhance patient selection criteria as well as develop additional therapeutic approaches.

Update on peanut allergy: Prevention and immunotherapy.

Background: The prevalence of food allergy is steadily increasing, and the burden of food allergy has become significant. However, treatments for food allergy remain experimental. Objective: To review advances in the past 18 months for the prevention and treatment of food allergies, with a particular focus on peanut allergy. Methods: Recently published trials on the use of oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and epicutaneous immunotherapy (EPIT) as well as updates on the implementation of the early introduction of peanut guidelines were identified. Results: To address the slow implementation of the early introduction of peanut guidelines, addendum guidelines were published by the National Institute of Allergy and Infectious Diseases, which provide broader and more practical guidelines across a wider range of patients. Well-known studies of OIT have supported its efficacy. Recent studies have shown the potential for sustained unresponsiveness (SU) in up to 50% of subjects after peanut OIT and an even higher proportion in toddlers who received peanut OIT. Adjustments in the protocol to address practicality and safety have shown potential for lower maintenance doses and faster buildups. Longer durations of peanut SLIT have shown successful desensitization to moderate amounts of peanut and may also show the potential for SU. EPIT has maintained an excellent safety profile with statistically significant response rates in children <11 years of age. Conclusion: Advances in food immunotherapy have continued to push the field forward and provided a better understanding of the safety and efficacy of OIT, SLIT, and EPIT. These treatments remain experimental, although phase III studies are currently underway.

Oral Immunotherapy Using Partially Hydrolyzed Formula for Cow’s Milk Protein Allergy: A Randomized, Controlled Trial

Background: Partially hydrolyzed cow’s milk protein-based formula (pHF) possesses low allergenicity. Here, we investigate the safety and efficacy of oral immunotherapy using pHF for children with cow’s milk protein allergy (CMPA). Objectives: A randomized, double-blind, controlled single-center trial was conducted to evaluate the efficacy and safety of pHF oral immunotherapy in children with CMPA. Methods: Participants were randomized into double-blind pHF-pHF and extensively hydrolyzed cow’s milk protein-based formula (eHF)-pHF groups. During this phase, the pHF-pHF group received pHF and the eHF-pHF group received eHF. During the open phase, all participants received pHF. The primary end point was a change in thresholds between baseline and the end of the first phase. Secondary end points were changes in thresholds between baseline and the end of the second phase, and casein-specific immunoglobulin (Ig)E, IgG₄, and basophil activation. Results: Twenty-five children, aged 1–9 years, were randomized into pHF-pHF and eHF-pHF groups. The threshold between baseline and the end of the first phase was significantly elevated in the pHF-pHF group (p = 0.048), but not in the eHF-pHF group. The threshold between other phases did not change significantly in either group. There were significant decreases in casein-specific IgE antibody levels between baseline and the second phase in the eHF-pHF group (p = 0.014). No participants suffered systemic allergic reactions requiring adrenaline or systemic corticosteroids after receiving the formulas. Conclusions: The results of this trial suggest that, in children with CMPA, tolerance to cow’s milk might be safely enhanced by intake of pHF, relative to that of eHF.

Cow’s Milk Allergy: Where have we Come from and where are we Going?

Since the 1930's the scientific literature on cow's milk protein allergy (CMPA) has accumulated. Over the last decade new diagnostic tools and treatment approaches have been developed. The diagnosis of reproducible adverse reactions to cow's milk proteins (CMP), i.e. CMPA, still has to be confirmed by controlled elimination and challenge procedures. Advanced diagnostic testing using epitope and microarray technology may in the future improve the diagnostic accuracy of CMPA by determination of specific IgE against specific allergen components of cow's milk protein. The incidence of CMPA in early childhood is approximately 2-3% in developed countries. Symptoms suggestive of CMPA may be encountered in 5-15% of infants emphasizing the importance of controlled elimination/milk challenge procedures. Reproducible clinical reactions to CMP in human milk have been reported in 0.5% of breastfed infants. Most infants with CMPA develop symptoms before 1 month of age, often within 1 week after inter introduction of CMP-based formula. The majority has two or more symptoms from two or more organ systems. Approximately 50-70% have cutaneous symptoms, 50-60% gastrointestinal symptoms and 20-30% respiratory symptoms. Symptoms may occur within 1 hour after milk intake (immediate reactions) or after 1 hour (late reactions). The prognosis of CMPA is good with a remission rate of approximately 45 to 50% at 1 year, 60 to 75% at 2 years and 85 to 90% at 3 years. Associated adverse reactions to other foods develop in up to 50% and allergy against inhalants in 50 to 80%. The basic treatment of CMPA is avoidance of CMP. In early childhood a milk substitute is needed. Documented extensively hydrolysed formulas are recommended, whereas partially hydrolysed formulas should not be used because of a high degree of antigenicity and allergenicity associated with adverse reactions. In case of intolerance to extensively hydrolysed formulas and multiple food allergies a formula based on aminoacids is recommended. Alternative milk substitutes such as sheep's and goat's milk should not be used because of a high degree of cross reactivity with CMP. Milk from other mammals such as mare and donkey may be tolerated by some children with CMPA. Soy protein is as allergenic as CMP and soy formula is not recommended for young children with CMPA because of a great risk of development of allergy to soy, whereas soymilk is normally tolerated in older children with CMPA. Recent treatment modalities are oral immunotherapy (OIT) involving the ingestion of increasing amounts of milk allergen on a regular basis to desensitize and potentially permanently tolerize patients to CMP. OIT can increase the reaction thresholds to CMP, but questions about safety and long-term efficacy remain. Anti-IgE therapy with Omalizumab may improve the safety and efficacy of OIT and may provide benefit in monotherapy.

Oral and sublingual peanut immunotherapy is not ready for general use

Food oral immunotherapy (OIT) is an investigational peanut allergy treatment aimed to achieve specific oral tolerance induction. Allergic children are given titrated oral (or sublingual) doses of their allergen on a daily basis, unlike in subcutaneous immunotherapy (SCIT). OIT is theorized to cause a shift from a Th2 to a Th1 regulatory environment, reflected by increases in food-specific IgG4/IgE, and the production of FoxP3. Peanut OIT holds special promise because peanut allergy has an unfavorable natural history and is rarely outgrown. A high percentage of the participants experience symptoms during peanut OIT, including anaphylaxis, warranting epinephrine and/or discontinuation of therapy. This is a concerning fact given that the studies have mostly targeted only older children, with less historical reactivity for enrollment. The handful of peanut OIT studies have shown that some participants can be desensitized to peanut, but none have shown that long-term tolerance can be reestablished. Factors predictive of which patients are most likely to succeed and become desensitized through OIT are unknown. Some private practices have begun offering peanut OIT as a therapy. Such practice is potentially dangerous given the safety and efficacy of OIT in randomized controlled clinical trials is still not well established. Therefore, until further investigation emerges that conclusively demonstrates OIT is safe, intermediate and long-term outcomes are better established, the number of participants that experience symptoms is reduced, and proof of concept established in patients of all ages, (irrespective of past reaction severity), OIT is not ready for use in the general allergy practice.

Efficacy of Oral Immunotherapy in Patients with Multiple Food Allergies

Efficacy of Oral Immunotherapy in Patients with Multiple Food Allergies

Efficacy of Oral Immunotherapy and Anti-IgE Antibody-Adjunctive Treatment in Patients with Multiple Food Allergies

Efficacy of Oral Immunotherapy and Anti-IgE Antibody-Adjunctive Treatment in Patients with Multiple Food Allergies

Oral Immunotherapy for Food Allergy: Towards a New Horizon

Food allergy has increased dramatically in prevalence over the past decade in westernized countries, and is now a major public health problem. Unfortunately for patients with food allergy, there is no effective therapy beyond food allergen avoidance, and rapid medical treatment for accidental exposures. Recently, oral immunotherapy (OIT) has been investigated as a treatment for this problem. In this review, we will discuss the progress in developing OIT for food allergy, including a novel approach utilizing Xolair (anti-IgE monoclonal antibody, omalizumab) in combination with OIT. This combination may enhance both the safety and efficacy of oral immunotherapy, and could lead to a widely available and safe therapy for food allergy.

Characteristics and natural course of neonatal and infantile gastrointestinal milk allergy and the efficacy of oral immunotherapy

SummaryThe characteristics and natural course of gastrointestinal (GI) allergies, which mainly affect infants and young children, are not fully determined. We investigated the nature of neonatal and infantile GI allergies and the efficacy of slow oral immunotherapy in patients with persistent symptoms. We observed 12 patients (five boys, seven girls) aged at first presentation from 0 days to 8 months after birth. Detailed interviews, peripheral blood eosinophil counts, antigen‐specific IgE antibody levels, antigen‐specific lymphocyte stimulation tests (LSTs), stool occult blood eosinophil counts and skin tests were performed in combination with milk elimination tests. Five patients underwent an intestinal mucosal biopsy. Provocation testing was used to assess tolerance acquisition. The only clinical symptom in six patients was bloody stool, while vomiting, fever, poor weight gain or hepatic dysfunction developed in six patients. Milk‐specific LSTs were positive in 10 of 11 cases tested. Lower GI endoscopy showed large numbers of infiltrating eosinophils in four of five patients with an intestinal mucosal biopsy. Provocation tests to confirm tolerance acquisition were performed in three patients. Interestingly, one patient suffered IgE‐mediated GI anaphylaxis during the provocation test. One patient had a sustained high LST index, and elimination of dairy milk products was continued. At 4 years of age, she underwent an oral challenge test. On ingestion of 5 mL of milk, she exhibited fever, loose stool, poor appearance and increased white blood cell counts, which was considered a positive provocation test. Therefore, slow oral immunotherapy was started using 1/20 of the threshold dose, with fat intake at least four times per week. This was steadily increased by 20% over 2 weeks without inducing symptoms. The characteristics of neonatal and infantile GI allergies are diverse, and they generally remit spontaneously. However, patients who do not develop tolerance may be suitable choices for oral immunotherapy.

The safety and efficacy of sublingual and oral immunotherapy for milk allergy

Oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) are potential therapies for food allergy, but the optimal method of administration, mechanism of action, and duration of response remain unknown. We sought to explore the safety and efficacy of OIT and SLIT for the treatment of cow's milk (CM) allergy. We randomized children with CM allergy to SLIT alone or SLIT followed by OIT. After screening double-blind, placebo-controlled food challenges and initial SLIT escalation, subjects either continued SLIT escalation to 7 mg daily or began OIT to either 1000 mg (the OITB group) or 2000 mg (the OITA group) of milk protein. They were challenged with 8 g of milk protein after 12 and 60 weeks of maintenance. If they passed the 60-week challenge, therapy was withdrawn, with challenges repeated 1 and 6 weeks later. Mechanistic correlates included end point titration skin prick testing and measurement of CM-specific IgE and IgG(4) levels, basophil histamine release, constitutive CD63 expression, CD203c expression, and intracellular spleen tyrosine kinase levels. Thirty subjects with CM allergy aged 6 to 17 years were enrolled. After therapy, 1 of 10 subjects in the SLIT group, 6 of 10 subjects in the SLIT/OITB group, and 8 of 10 subjects in the OITA group passed the 8-g challenge (P= .002, SLIT vs OIT). After avoidance, 6 of 15 subjects (3 of 6 subjects in the OITB group and 3 of 8 subjects in the OITA group) regained reactivity, 2 after only 1 week. Although the overall reaction rate was similar, systemic reactions were more common during OIT than during SLIT. By the end of therapy, titrated CM skin prick test results and CD63 and CD203c expression decreased and CM-specific IgG(4) levels increased in all groups, whereas CM-specific IgE and spontaneous histamine release values decreased in only the OIT group. OIT was more efficacious for desensitization to CM than SLIT alone but was accompanied by more systemic side effects. Clinical desensitization was lost in some cases within 1 week off therapy.

Safety and efficacy of oral immunotherapy with standardized cat extract

Fifty-three subjects with positive skin prick test results to cat extract and rhinoconjunctival symptoms on exposure to cat dander were enrolled in a double-blind, placebo-controlled study of oral cat immunotherapy. Responses were assessed by development of symptoms and nasal blockage on exposure to an apartment contaminated with cat dander, by titrated skin prick tests, and by cat-specific IgG and IgE. A total cumulative dose of 2.5 x 10 6 allergy units or 436 U Fel d I were administered over a period of 3 months. Both groups of subjects had significantly fewer symtpoms on exposure to cat dander during the course of the study, but there was no significant difference between active and placebo groups. There were no significant changes in either group in nasal blockage, skin prick test results, or specific IgG levels. Both groups had significant increases in cat-specific IgE, but there were no differences between groups. Subjects receiving active treatment had a slight excess of gastrointestinal complaints. Two subjects receiving active treatment experienced systemic symptoms: one had pulmonary edema, and the other had persistent asthma and urticaria, which may have represented reactions to the treatment. We conclude that oral cat immunotherapy with the preparation and doses used in this study is not effective.