Oral Immunotherapy For Peanut Allergy Research Articles

Longer-Term Safety and Efficacy Measures of AR101 Oral Immunotherapy for Peanut Allergy: Results from a Phase 3 Follow-On Study

Longer-Term Safety and Efficacy Measures of AR101 Oral Immunotherapy for Peanut Allergy: Results from a Phase 3 Follow-On Study

Efficacy and safety of oral immunotherapy for peanut allergy: a pilot study in Singaporean children.

BackgroundPeanut allergy is an increasing problem in Singapore and strict avoidance is difficult as peanut is ubiquitous in Asian cuisine.ObjectiveWe aimed to assess the efficacy and safety of peanut oral immunotherapy (OIT) in children with obvious peanut allergy in Singapore.MethodsThis was an open-label study of peanut OIT in children living in Singapore, with 2 weekly dose escalation until final maintenance dose of 3,000 mg of peanut protein and a maintenance phase of 12 months. An oral food challenge was performed at 6 months to assess for desensitisation and at 4 weeks after discontinuation of OIT having completed 12 months of maintenance therapy to assess for possible sustained unresponsiveness. The adverse events were monitored using the symptom diaries.ResultsNine subjects were started on OIT, with 7 managing to complete maintenance phase of therapy. Of these 7, all were able to tolerate at least 3,000 mg of peanut protein by 6 months of maintenance therapy, showing that the OIT was effective. Of these 7, 3 patients complied with the 4-week abstinence period after completion of OIT before another peanut challenge; 2 of the 3 subjects showed a significant decrease from the initial ability to tolerate 3,000 mg of peanut protein. Side effects were mainly gastrointestinal in nature and were more common during the updosing phase than the maintenance phase. No episodes of anaphylaxis were observed in this study.ConclusionPeanut OIT seemed to be effective and safe in our cohort of Singaporean children.

Efficacy and Safety of AR101 in Oral Immunotherapy for Peanut Allergy: Results of ARC001, a Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial

JA Bird, JM Spergel, SM Jones. J Allergy Clin Immunol Pract. 2018;6(2):476–485 To investigate the efficacy and safety of the novel oral biologic peanut oral immunotherapy (OIT) drug product, AR101, in a phase II multicenter study. Subjects aged 4 to 26 years meeting the following criteria were included: a clinical history of peanut allergy, positive skin or blood peanut immunoglobulin E test result, and reaction to <143 mg of peanut protein in the screening double-blind, placebo-controlled food challenge (DBPCFC). Subjects with a history of life-threatening anaphylaxis or poorly controlled asthma were excluded. In this randomized controlled trial, subjects were randomly assigned 1:1 to receive either AR101 (a defatted peanut …

AR101 Oral Immunotherapy for Peanut Allergy

BackgroundPeanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions.MethodsIn a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms.ResultsOf the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; P<0.001). During the exit food challenge, the maximum severity of symptoms was moderate in 25% of the participants in the active-drug group and 59% of those in the placebo group and severe in 5% and 11%, respectively. Adverse events during the intervention period affected more than 95% of the participants 4 to 17 years of age. A total of 34.7% of the participants in the active-drug group had mild events, as compared with 50.0% of those in the placebo group; 59.7% and 44.4% of the participants, respectively, had events that were graded as moderate, and 4.3% and 0.8%, respectively, had events that were graded as severe. Efficacy was not shown in the participants 18 years of age or older.ConclusionsIn this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. (Funded by Aimmune Therapeutics; PALISADE ClinicalTrials.gov number, NCT02635776.)

Real-World Experience with Peanut Oral Immunotherapy: Lessons Learned From 270 Patients

Peanut allergy (PA) is a significant and increasing problem, interfering with psychological development and family life. The standard recommendation to avoid peanut products and have access to injectable epinephrine is often inadequate. Oral immunotherapy for PA has been formally studied. Clinical observations of allergen immunotherapy have repeatedly enhanced patient care. The purpose of this study was to report observations on the treatment of 270 patients with PA over 8.5years. This is a retrospective record review of patients beginning peanut oral immunotherapy between January 1, 2009, and June 1, 2017, approved by the North Texas Institutional Review Board. A total of 270 patients aged 4 to 18 years comprising 107 girls and 163 boys were treated. A total of 214 of 270 patients (79%) completed immunotherapy escalation. Age (P<.001) and peanut IgE (P < .001) correlate inversely with completing dose escalation. Epinephrine-treated reactions in 63and isolated gastrointestinal symptoms in 101 patients, respectively, were the most common adverse reactions to treatment but did not preclude success. Peanut IgE decreased by 65% after 3 years of maintenance treatment and 14 of 214 patients (6.5%) were able to achieve sustained unresponsiveness. In an allergy office practice setting, 79% of patients are able to complete a peanut desensitization protocol and maintain the desensitized state indefinitely with daily dosing. With appropriate planning and precautions, peanut oral immunotherapy may be performed in an allergy office. Careful observations of clinical treatment can contribute to the development of effective treatment strategies.

Efficacy and Safety of AR101 in Oral Immunotherapy for Peanut Allergy: Results of ARC001, a Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial

Peanut oral immunotherapy, using a variety of approaches, has been previously shown to induce desensitization in peanut-allergic subjects, but no products have been approved for clinical use by regulatory agencies. We performed the first phase 2 multicentered study to assess the safety and efficacy of AR101, a novel oral biologic drug product. A randomized, double-blind, placebo-controlled trial was conducted at 8 US centers. Eligible subjects were 4 to 26 years old, sensitized to peanut, and had dose-limiting symptoms to ≤143 mg of peanut protein in a screening double-blind, placebo-controlled food challenge (DBPCFC). Subjects were randomized 1:1 to daily AR101 or placebo and gradually up-dosed from 0.5 to 300 mg/day. The primary endpoint was the proportion of subjects in each arm able to tolerate ≥443 mg (cumulative peanut protein) at exit DBPCFC with no or mild symptoms. Fifty-five subjects (29 AR101, 26 placebo) were enrolled. In the intention-to-treat analysis, 23 of 29 (79%) and 18 of 29 (62%) AR101 subjects tolerated ≥443 mg and 1043 mg at exit DBPCFC, respectively, versus 5 of 26 (19%) and 0 of 26 (0%) placebo subjects (both P < .0001). Compared with placebo, AR101 significantly reduced symptom severity during exit DBPCFCs and modulated peanut-specific cellular and humoral immune responses. Gastrointestinal (GI) symptoms were the most common treatment-related adverse events (AEs) in both groups, with 6 AR101 subjects (21%) withdrawing, 4 of those due primarily to recurrent GI AEs. In this study, AR101 demonstrated an acceptable safety profile and demonstrated clinical activity as a potential immunomodulatory treatment option in peanut-allergic children over the age of 4, adolescents, and young adults.

Oral Immunotherapy for Peanut Allergy.

Peanut allergy is a common disease and the cause of severe, life-threatening allergic reactions and death. It is rarely outgrown; most pediatric patients carry the disease into adulthood. Peanut allergy poses a significant burden on the quality of life of sufferers and their families, which results mainly from the fear of accidental peanut ingestion but is also due to dietary and social restrictions. Current standard management involves avoidance advice, patient education, and provision of emergency rescue medication. Immunotherapy, commonly used to treat other allergic diseases, has shown promise as a disease-modifying therapy for peanut allergy. Results from studies of oral immunotherapy show high efficacy rates, improvement in quality of life, and a good safety profile. Treatment may result in sustained unresponsiveness in a proportion of patients, whereas others require ongoing treatment.

Impact of Sublingual and Oral Immunotherapy for Peanut Allergy on Blood Dendritic Cells

Impact of Sublingual and Oral Immunotherapy for Peanut Allergy on Blood Dendritic Cells

Oral immunotherapy for peanut allergy in clinical practice is ready

Oral immunotherapy (OIT) for peanut allergy is ready for clinical allergy practice. Some physicians, particularly at academic centers, believe that OIT is not ready for clinical practice. The shortcomings of the present general recommendations of food avoidance and provision of epinephrine autoinjectors for a select number of patients demand a different approach. In peanut-allergic patients, the rate of accidental reactions is ~10% annually. Between 1 and 2% of these reactions require epinephrine or emergency department visits. Food allergy and peanut allergy, specifically, have a large negative impact on the quality of life (QOL) for patients and their families, which can be psychosocially debilitating. These decreases in health-related QOL continue into adulthood. There is only an ~20% chance of spontaneous remission in peanut allergy. Given this climate, three private allergy practices have begun providing OIT to 150 patients with peanut anaphylaxis. One hundred eleven (74%) patients were able to tolerate eight peanuts (8 g, ~2 g of protein). During outpatient dosing, epinephrine was used at a rate of 8 per 10,000 doses. To date, there have been no long-term (>24-36 months) unexpected reactions. OIT decreases risk and in one study, conducted in a practice setting, it was shown to improve QOL. OIT is a meaningful clinical procedure that can help our patients.

Allergen-specific oral immunotherapy for peanut allergy.

Peanut allergy is one of the most common forms of food allergy encountered in clinical practice. In most cases, it does not spontaneously resolve; furthermore, it is frequently implicated in acute life-threatening reactions. The current management of peanut allergy centres on meticulous avoidance of peanuts and peanut-containing foods. Allergen-specific oral immunotherapy (OIT) for peanut allergy aims to induce desensitisation and then tolerance to peanut, and has the potential to revolutionise the management of peanut allergy. However, at present there is still considerable uncertainty about the effectiveness and safety of this approach. To establish the effectiveness and safety of OIT in people with IgE-mediated peanut allergy who develop symptoms after peanut ingestion. We searched in the following databases: AMED, BIOSIS, CAB, CINAHL, The Cochrane Library, EMBASE, Global Health, Google Scholar, IndMed, ISI Web of Science, LILACS, MEDLINE, PakMediNet and TRIP. We also searched registers of on-going and unpublished trials. The date of the most recent search was January 2012. Randomised controlled trials (RCTs), quasi-RCTs or controlled clinical trials involving children or adults with clinical features indicative of IgE-mediated peanut allergy treated with allergen-specific OIT, compared with control group receiving either placebo or no treatment, were eligible for inclusion. Two review authors independently checked and reviewed titles and abstracts of identified studies and assessed risk of bias. The full text of potentially relevant trials was assessed. Data extraction was independently performed by two reviewers with disagreements resolved through discussion. We found one small RCT, judged to be at low risk of bias, that enrolled 28 children aged 1 to 16 years with evidence of sensitisation to peanut and a clinical history of reaction to peanut within 60 minutes of exposure. The study did not include children who had moderate to severe asthma or who had a history of severe peanut anaphylaxis. Randomisation was in a 2:1 ratio resulting in 19 children being randomised to the intervention arm and nine to the placebo arm. Intervention arm children received OIT with peanut flour and control arm participants received placebo comprising of oat flour. The primary outcome was assessed using a double-blind, placebo controlled oral food challenge (OFC) at approximately one year. No data were available on longer term outcomes beyond the OFC conducted at the end of the study.Because of adverse events, three patients withdrew from the intervention arm before the completion of the study. Therefore, only 16 participants received the full course of peanut OIT, whereas all nine patients receiving placebo completed the trial. The per-protocol analysis found a significant increase in the threshold dose of peanut allergen required to trigger a reaction in those in the intervention arm with all 16 participants able to ingest the maximum cumulative dose of 5000 mg of peanut protein (which the authors equate as being equivalent to approximately 20 peanuts) without developing symptoms, whereas in the placebo group they were able to ingest a median cumulative dose of 280 mg (range: 0 to 1900 mg, P < 0.001) before experiencing symptoms. Per-protocol analyses also demonstrated that peanut OIT resulted in reductions in skin prick test size (P < 0.001), interleukin-5 (P = 0.01), interleukin-13 (P = 0.02) and an increase in peanut-specific immunoglobulin G(4) (IgG(4)) (P < 0.01).Children in the intervention arm experienced more adverse events during treatment than those in the placebo arm. In the initial day escalation phase, nine (47%) of the 19 participants initially enrolled in the OIT arm experienced clinically-relevant adverse events which required treatment with H(1)-antihistamines, two of which required additional treatment with epinephrine (adrenaline). The one small RCT we found showed that allergen-specific peanut OIT can result in desensitisation in children, and that this is associated with evidence of underlying immune-modulation. However, this treatment approach was associated with a substantial risk of adverse events, although the majority of these were mild. In view of the risk of adverse events and the lack of evidence of long-term benefits, allergen-specific peanut OIT cannot currently be recommended as a treatment for the management of patients with IgE-mediated peanut allergy. Larger RCTs are needed to investigate the acceptability, long-term effectiveness and cost-effectiveness of safer treatment regimens, particularly in relation to the induction of clinical and immunological tolerance.