Oral Immunotherapy For Peanut Allergy Research Articles

Safety and adherence of early oral immunotherapy for peanut allergy in a primary care setting: a retrospective cross-sectional study

BackgroundPeanut allergy is a common food allergy with potentially life-threatening implications. Early oral immunotherapy for peanut allergy (P-EOIT) has been shown to be effective and safe in research and specialty clinic settings. Provision of P-EOIT in primary care would make it available to more patients. We sought to assess the safety of P-EOIT in a primary care setting by documenting the rates of peanut-related allergic reactions leading to emergency department (ED) visits and use of epinephrine. We also examined adherence by assessing the percentage of patients reaching maintenance phase and continuing ingestion after one year of P-EOIT.MethodsThis retrospective study included all patients aged less than 36 months who started P-EOIT at a primary care allergy clinic in New Brunswick, Canada, from 2016 to 2020. The population included patients who (1) had a history of an allergic reaction to peanuts with a positive skin prick test or positive peanut specific IgE level (ps-IgE) or (2) no history of ingestion and a baseline ps-IgE ≥5 kU/L. Patients had biweekly clinic visits with graded increases in peanut protein up to a maintenance dose of 300 mg of peanut protein daily. A blinded retrospective review of paper charts and electronic medical records was conducted along with phone interviews regarding ED visits and epinephrine use.ResultsAll 69 consented patients reached maintenance dose over a median of 29 weeks, and 66 patients (95.7%) were still regularly consuming peanut protein after 1 year of maintenance. One patient had a peanut ingestion-related ED visit requiring epinephrine during the escalation phase of peanut protein dosing (1.4%). During the first year of maintenance phase, no patients had peanut ingestion-related ED visits nor required epinephrine.ConclusionEarly oral immunotherapy for peanut allergy in a primary care setting appears to be safe and our findings suggest that it does not lead to an increased burden of emergency department visits. Our population had high adherence rates, with the majority achieving maintenance dose and staying on this dose for one year.

Oral Immunotherapy for Peanut Allergy in Children 1 to Less Than 4 Years of Age

BackgroundPeanut allergy is a common childhood allergy, and the only approved treatment for children 4 to 17 years of age is peanut allergen powder-dnfp (PTAH) oral immunotherapy.MethodsFor this phase 3, randomized, double-blind, placebo-controlled trial, we enrolled peanut-allergic children 1 to <4 years of age who experienced dose-limiting symptoms from ≤300 mg peanut protein during a screening double-blind, placebo-controlled food challenge (DBPCFC). Participants received PTAH or placebo, randomized in a 2:1 ratio, for approximately 12 months. At the trial conclusion, all participants underwent an exit BDPCFC. The primary end point was desensitization (i.e., tolerating a ≥600-mg single dose of peanut protein with only mild allergy symptoms).ResultsIn the PTAH-treated group (n=98), 73.5% of participants tolerated a single dose of ≥600 mg peanut protein at exit DBPCFC compared with 6.3% in the placebo group (n=48). Most participants experienced an adverse event (98.0% of PTAH-treated and 97.9% of placebo-treated participants), which was mild or moderate in grade for 93.2% of participants (92.9% in PTAH-treated and 93.8% in placebo-treated participants). Treatment-related adverse events, which were mild to moderate, were experienced by 75.5% of PTAH-treated and 58.3% of placebo-treated participants. Three treatment-related systemic allergic reactions, none of which were severe or serious in grade, were noted in two PTAH-treated participants (2%).ConclusionsIn peanut-allergic children 1 to <4 years of age treated with PTAH for approximately 12 months, the majority tolerated all peanut protein dose levels assessed. PTAH-treated patients had more treatment-related adverse events, which were mild to moderate severity. (Funded by Aimmune Therapeutics; ClinicalTrials.gov number, NCT03736447.)

Long-term safety and immunologic outcomes of daily oral immunotherapy for peanut allergy.

Oral immunotherapy containing peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) (Palforzia [Aimmune Therapeutics, Brisbane, Calif]) for 9 to 12 months resulted in higher tolerated amounts of peanut protein in PTAH-treated individuals aged 4 to 17 years with peanut allergy than in placebo-treated participants. We aimed to describe additional long-term pooled safety data and changes in peanut sensitization markers from baseline through approximately 5 years of treatment. The results from 6 clinical trials of PTAH (3 controlled and 3 open-label extension studies [N= 1227]) were pooled, and analysis of safety outcomes and immunologic data was performed. The PTAH doses were administered sequentially as follows: initial dose escalation (dose increased to 6 mg over 2 days), updosing (dose increased every 2 weeks to 300 mg for a minimum of 6 months), and maintenance dosing (300 mg per day). There was a trend toward decreased adverse events (AEs) at years 1 and 2 that was maintained up to 5 years, with 94% of patients experiencing mild or moderate AEs and only 13% discontinuing PTAH use because of AEs overall. Gastrointestinal symptoms were the most commonly reported treatment-related AEs. Adownward trend in systemic allergic reactions was also reported. PTAH treatment resulted in reduced levels of peanut-specific IgE after the first year and increased levels of peanut-specific IgG4, with a lowered peanut-specific IgE:IgG4 ratio. Areduction in median peanut skin prick test wheal diameter was observed (11.50 mm at baseline vs 5.75 mm at year 5). Long-term immunomodulation without any new safety signals was reported with PTAH immunotherapy in the largest safety data set and longest treatment duration for oral immunotherapy published to date.

Post hoc analysis examining symptom severity reduction and symptom absence during food challenges in individuals who underwent oral immunotherapy for peanut allergy: results from three trials

PurposePeanut allergy and its current management, involving peanut avoidance and use of rescue medication during instances of accidental exposure, are burdensome to patients and their caregivers and can be a source of stress, uncertainty, and restriction. Physicians may also be frustrated with a lack of effective and safe treatments other than avoidance in the current management of peanut allergy. Efficacy, determined using double-blind, placebo-controlled food challenges (DBPCFCs), of oral immunotherapy with peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; Palforzia®) was demonstrated versus placebo in children and adolescents aged 4 to 17 years in multiple phase 3 trials; continued benefit of PTAH was shown in a follow-on trial. The DBPCFC is a reproducible, rigorous, and clinically meaningful assessment accepted by regulatory authorities to evaluate the level of tolerance as an endpoint for accidental exposures to peanut in real life. It also provides useful clinical and patient-relevant information, including the amount of peanut protein an individual with peanut allergy can consume without experiencing dose-limiting symptoms, severity of symptoms, and organs affected upon ingestion of peanut protein. We explored symptoms of peanut exposure during DBPCFCs from phase 3 and follow-on trials of PTAH to further characterize treatment efficacy from a perspective relevant to patients, caregivers, and clinicians.MethodsSymptom data recorded during screening and/or exit DBPCFCs from participants aged 4 to 17 years receiving PTAH or placebo were examined post hoc across three PTAH trials (PALISADE [ARC003], ARC004 [PALISADE follow-on], and ARTEMIS [ARC010]). The maximum peanut protein administered as a single dose during DBPCFCs was 1000 mg (PALISADE and ARTEMIS) and 2000 mg (ARC004). Symptoms were classified by system organ class (SOC) and maximum severity. Endpoints were changes in symptom severity and freedom from symptoms (ie, asymptomatic) during DBPCFC. Relative risk (RR) was calculated for symptom severity by SOC and freedom from symptoms between groups; descriptive statistics were used to summarize all other data.ResultsThe risk of any respiratory (RR 0.42 [0.30–0.60], P < 0.0001), gastrointestinal (RR 0.34 [0.26–0.44], P < 0.0001), cardiovascular/neurological (RR 0.17 [0.08–0.39], P < 0.001), or dermatological (RR 0.33 [0.22–0.50], P < 0.0001) symptoms was significantly lower in participants treated with PTAH versus placebo upon exposure to peanut at the end of the PALISADE trial (ie, exit DBPCFC). Compared with placebo-treated participants (23.4%), the majority (76.3%) of PTAH-treated participants had no symptoms at the exit DBPCFC when tested at the peanut protein dose not tolerated (ie, reactive dose) during the screening DBPCFC. Significantly higher proportions of PTAH-treated participants were asymptomatic at doses ≤ 100 mg in the exit DBPCFC compared with placebo-treated participants (PALISADE: 69.35% vs 12.10%, RR 5.73 [95% confidence interval (CI) 3.55–9.26]; P < 0.0001; ARTEMIS: 67.42% vs 13.95%, RR 4.83 [95% CI 2.28–10.25]; P < 0.0001); findings were similar at peanut protein doses ≤ 1000 mg (PALISADE: RR 15.56 [95% CI 5.05–47.94]; P < 0.0001; ARTEMIS: RR 34.74 [95% CI 2.19–551.03]; P < 0.0001). In ARC004, as the period of PTAH maintenance became longer, greater proportions of participants were asymptomatic at doses of peanut protein ≤ 1000 mg in the exit DBPCFC (from 37.63% after ~ 6 months of maintenance treatment [exit DBPCFC of PALISADE] to 45.54% after ~ 13 months and 58.06% after ~ 20 months of overall PTAH maintenance treatment).ConclusionsPTAH significantly reduced symptom severity due to exposure to peanut, which is clinically relevant. When exposed to peanut, participants with peanut allergy treated with PTAH rarely had moderate or severe respiratory or cardiovascular/neurological symptoms. Oral immunotherapy with PTAH appears to reduce frequency and severity of allergic reactions in individuals with peanut allergy after accidental exposure to peanut and may enable them and their families to have an improved quality of life.Trial registration ClinicalTrials.gov, NCT02635776, registered 17 December 2015, https://clinicaltrials.gov/ct2/show/NCT02635776?term=AR101&draw=2&rank=7; ClinicalTrials.gov, NCT02993107, registered 08 December 2016, https://clinicaltrials.gov/ct2/show/NCT02993107?term=AR101&draw=2&rank=6; ClinicalTrials.gov, NCT03201003, registered 22 June 2017, https://clinicaltrials.gov/ct2/show/NCT03201003? term = AR101&draw = 2&rank = 9

Transitioning from epicutaneous to oral peanut immunotherapy.

Epicutaneous immunotherapy (EPIT) has been tested in clinical trials for children with peanut allergy (PA) for its safety and efficacy in inducing desensitization. Aside from peanut avoidance and symptom management, oral immunotherapy (OIT) is another option for PA patients. However, OIT can be associated with adverse events and pose safety concerns to children and their caregivers. This study assessed 27 children who successfully completed a peanut EPIT trial. 18 of them transitioned to peanut OIT with starting doses ranging from 10-600 mg of peanut protein. Our aim was to learn more about the EPIT to OIT experience through descriptive survey responses and to gather information that may support the sequential use of the two immunotherapies for safe and positive outcomes that may not be achieved by either alone. Overall, children and their caregivers had less anxiety about starting OIT after having had peanut exposure through EPIT. Most children who transitioned from EPIT to OIT had no or minor symptoms initially, with symptoms lessening later in OIT. Most were also able to maintain or increase their peanut dose over time, achieving maintenance doses of 60-2,000 mg. In comparison with current literature on OIT for PA in children, the reported symptoms appeared less severe and less prevalent in the EPIT to OIT group. However, there were 3 participants who withdrew from OIT due to the development of intolerable symptoms. This study provides initial data in support of EPIT to OIT, and larger randomized controlled trials assessing effectiveness of the two therapies together are warranted.

Allergen immunotherapy: past, present and future.

Allergen immunotherapy is a form of therapeutic vaccination for established IgE-mediated hypersensitivity to common allergen sources such as pollens, house dust mites and the venom of stinging insects. The classical protocol, introduced in 1911, involves repeated subcutaneous injection of increasing amounts of allergen extract, followed by maintenance injections over a period of 3 years, achieving a form of allergen-specific tolerance that provides clinical benefit for years after its discontinuation. More recently, administration through the sublingual route has emerged as an effective, safe alternative. Oral immunotherapy for peanut allergy induces effective ‘desensitization’ but not long-term tolerance. Research and clinical trials over the past few decades have elucidated the mechanisms underlying immunotherapy-induced tolerance, involving a reduction of allergen-specific T helper 2 (TH2) cells, an induction of regulatory T and B cells, and production of IgG and IgA ‘blocking’ antibodies. To better harness these mechanisms, novel strategies are being explored to achieve safer, effective, more convenient regimens and more durable long-term tolerance; these include alternative routes for current immunotherapy approaches, novel adjuvants, use of recombinant allergens (including hypoallergenic variants) and combination of allergens with immune modifiers or monoclonal antibodies targeting the TH2 cell pathway.

Induction of food-specific IgG by Gene Gun-delivered DNA vaccines

Shellfish and tree nut allergies are among the most prevalent food allergies, now affecting 2%-3% and 1% of the US population, respectively. Currently, there are no approved therapies for shellfish or tree nut allergies, with strict avoidance being the standard of care. However, oral immunotherapy for peanut allergy and subcutaneous immunotherapy for environmental allergens are efficacious and lead to the production of allergen-specific IgG, which causes suppression of allergen effector cell degranulation. Since allergen-specific IgG is a desired response to alleviate IgE-mediated allergies, we tested transcutaneously-delivered DNA vaccines targeting shellfish and tree nut allergens for their ability to induce antigen-specific IgG, which would have therapeutic potential for food allergies. We assessed Gene Gun-delivered DNA vaccines targeting either crustacean shellfish or walnut/pecan allergens, with or without IL-12, in naïve mice. Three strains of mice, BALB/cJ, C3H/HeJ and CC027/GeniUnc, were evaluated for IgG production following vaccination. Vaccines were administered twice via Gene Gun, three weeks apart and then blood was collected three weeks following the final vaccination. Vaccination with shellfish allergen DNA led to increased shrimp-specific IgG in all three strains, with the highest production in C3H/HeJ from the vaccine alone, whereas the vaccine with IL-12 led to the highest IgG production in BALB/cJ and CC027/GeniUnc mice. Similar IgG production was also induced against lobster and crab allergens. For walnut/pecan vaccines, BALB/cJ and C3H/HeJ mice produced significantly higher walnut- and pecan-specific IgG with the vaccine alone compared to the vaccine with IL-12, while the CC027 mice made significantly higher IgG with the addition of IL-12. Notably, intramuscular administration of the vaccines did not lead to increased antigen-specific IgG production, indicating that Gene Gun administration is a superior delivery modality. Overall, these data demonstrate the utility of DNA vaccines against two lifelong food allergies, shellfish and tree nuts, suggesting their potential as a food allergy therapy in the future.

Onset of eosinophilic esophagitis during a clinical trial program of oral immunotherapy for peanut allergy

Onset of eosinophilic esophagitis during a clinical trial program of oral immunotherapy for peanut allergy

Continuous and Daily Oral Immunotherapy for Peanut Allergy: Results from a 2-Year Open-Label Follow-On Study

The randomized, controlled PALISADE trial demonstrated the benefit of daily oral immunotherapy with Peanut (Arachis Hypogaea) allergen powder-dnfp (PTAH, formerly AR101) in peanut-allergic children and adolescents. ARC004, the open-label follow-on study to PALISADE, used 5 dosing cohorts to explore PTAH treatment beyond 1 year and alternative dosing regimens in peanut-allergic individuals. Active arm (PTAH-continuing) PALISADE participants who tolerated 300-mg peanut protein at the exit double-blind placebo-controlled food challenge and placebo arm (PTAH-naive) participants could enter ARC004. PTAH-continuing participants were assigned to receive daily (cohorts 1 and 3A) or non-daily (cohorts 2, 3B, and 3C) dosing regimens; PTAH-naive participants were built up to 300 mg/d PTAH, followed by maintenance dosing. At study completion, participants underwent an exit double-blind placebo-controlled food challenge with doses up to 2000 mg peanut protein. Data were assessed using descriptive statistics. Overall, 358 (87.5%) eligible participants (4-17 years) entered ARC004 (PTAH-continuing, n= 256; PTAH-naive, n= 102). Among PTAH-continuing participants, exposure-adjusted adverse event rates were 12.94 to 17.54/participant-year and 25.95 to 42.49/participant-year in daily and non-daily dosing cohorts, respectively; most participants (83%) experienced mild or moderate adverse events. Daily dosing cohorts appeared to have higher desensitization rates than non-daily dosing cohorts. Of all PTAH-continuing cohorts, cohort 3A had the longest daily dosing duration and the highest desensitization rates. Changes in immune markers with PTAH continuation demonstrated ongoing immunomodulation. Outcomes in PTAH-naive participants mirrored those of the PALISADE active arm. Continued daily PTAH treatment beyond 1 year showed sustained safety and efficacy. Ongoing immunomodulation was observed during the second year of treatment.

M312 COMORBID FOOD PROTEIN INDUCED ENTEROCOLITIS SYNDROME AND ANAPHYLAXIS DUE TO PEANUT

Food protein induced enterocolitis syndrome (FPIES) is distinct from anaphylaxis. FPIES involves different clinical features, including typical causative foods and higher threshold doses. A patient with both conditions due to peanut presented as symptomatic FPIES in the course of oral immunotherapy for peanut allergy.

Oral immunotherapy for peanut allergy: a systematic review and meta-analysis

Oral immunotherapy for peanut allergy: a systematic review and meta-analysis

Peanut Allergen Powder-dnfp: A Novel Oral Immunotherapy to Mitigate Peanut Allergy.

To review data on efficacy and safety of peanut allergen powder-dnfp (PAP; Palforzia), a novel oral immunotherapy for peanut allergy, a common food allergy. A PubMed/CINAHL search in English was performed from inception to June 30, 2020, using the search words peanut allergy, desensitization, ARA101, and peanut oral immunotherapy. Published phase 2 and 3 clinical trials, documents presented to the Food and Drug Administration, and supplemental study documentation were reviewed. Articles evaluated PAP's pharmacology, pharmacokinetics, mechanism of action, efficacy, and safety. PAP was efficacious and safe for treatment of peanut allergy in mostly Caucasian children, 4 to 17 years old. A key phase III clinical trial showed a statistically significant difference (primary end point) between PAP 600 mg and placebo groups (67.2% vs 4%; P < 0.001). During initial dose escalation and updosing phases, gastrointestinal and respiratory tract allergic reactions (ARs) were more common in the PAP group. More epinephrine rescue was used in the PAP group. Oral immunotherapy for desensitization of peanut allergy was shown to reduce the severity of reactions if accidental allergen exposure occurs. Risk evaluation and mitigation strategy certification is required for pharmacies, health care providers, and clinics. More data in real-world populations will enhance its effectiveness. In patients 4 to 17 years old, PAP mitigated ARs, including anaphylaxis, that may occur with accidental peanut exposure. Although there are risks, it was efficacious in more than two-thirds of participants in phase 2 and phase 3 efficacy trials.

First Oral Immunotherapy for Peanut Allergy.

Peanut (Arachis hypogaea) allergen powder-dnfp (Palforzia) is the first oral immunotherapy for children ages four to 17 years who have been diagnosed with a peanut allergy.Like subcutaneous forms of immunotherapy, Palforzia introduces the allergen in increasing doses and risks inducing allergic responses, including anaphylaxis.

Sustained outcomes in oral immunotherapy for peanut allergy (POISED study): a large, randomised, double-blind, placebo-controlled, phase 2 study

Dietary avoidance is currently recommended for peanut allergies. We evaluated sustained effects of treating peanut allergy with oral immunotherapy (OIT) in the first phase 2 randomized-controlled long-term study in adults and children. In a double-blind, placebo-controlled, randomized study, 120 peanut-allergic participants (7-53 years old) received up to 4 g of peanut protein or placebo daily for 3 years. Participants received placebo (N=25) or peanut protein (N=95) over 104 weeks; 60 then discontinued (peanut-0) while 35 received 300 mg daily (peanut-300). Double-blind, placebo-controlled food challenges (DBPCFCs) to 4 g peanut protein were conducted at baseline, week 104, and every 13 weeks thereafter for one year. The primary endpoint was reached at week 117 after 3 months of discontinuation (testing sustained unresponsiveness): 21/60 (35%) peanut-0 participants passed the challenge with no reaction versus 1/25 (4%) placebo (primary endpoint, P=0.002). Time to failure was significantly longer in peanut-300 vs. peanut-0 vs. placebo arms (P<0.0001). The percentage of participants passing DBPCFCs in peanut-300 declined significantly (weeks 104 vs. 156; 83% vs. 37%, P<0.001). Adverse allergic reactions decreased over time in all arms. Peanut-specific IgG4/IgE levels were higher (P<0.001), and Ara h 2-specific IgE (P<0.001) and basophil activation responses (P=0.037) were lower, at baseline in those achieving sustained unresponsiveness at week 117. Peanut OIT desensitizes most peanut-allergic individuals to 4 g peanut protein but discontinuation, or even a reduction to 300 mg daily, increases the likelihood of regaining clinical reactivity to peanut. Baseline blood tests correlate with week 117 treatment outcomes.

Food Oral Immunotherapy for Peanut Allergy

Food Oral Immunotherapy for Peanut Allergy

AR101 Oral Immunotherapy for Peanut Allergy

To determine if AR101 is a safe and effective treatment to prevent peanut reactions due to accidental exposure.Participants (496, 4–17 years old) were randomly assigned 3:1 to receive AR101 (peanut-derived investigational drug) or placebo (oat flour). The majority of the participants had a history of peanut anaphylaxis (72%), asthma (53%), and multiple food allergies (66%). All participants had dose-limiting symptoms at a dose of 100 mg of peanut protein in a double-blind placebo-controlled food challenge at baseline.Participants began a 1-day supervised dose escalation phase from 0.5 to 6 mg. The dose was then increased gradually every 2 weeks from 3 to 300 mg. A maintenance dose of 300 mg was continued for 24 weeks.A double-blind placebo-controlled food challenge was done at the end of the trial. Among the participants, 250 of the 372 (67.2%) in the active drug group and 5 of 124 (4%) in the placebo group were able to tolerate a dose of 600 mg or more of peanut protein without dose-limiting symptoms. The key secondary endpoints were tolerating 300 mg (76.6%) or 1000 mg (50.3%) compared with those in the placebo group (8.1% and 2.4%, respectively). Severe reactions occurred in 4.3% of the active drug group and 0.8% of the placebo group. Participants in the active treatment group compared with placebo had a higher incidence of gastrointestinal events (85.8% vs 69.4%), respiratory tract events (81.2% vs 71.8%), skin reactions (66.9% vs 55.6%), and immune system concerns (68.9% vs 8.9%). Overall, 43 (11.6%) in the active treatment group and 3 (2.4%) in the placebo group withdrew because of adverse events. Gastrointestinal symptoms causing study withdrawal occurred in 6.5% of the active treatment group and 1.2% of the placebo group. During the course of the trial, 52 participants (14%) in the active drug group and 8 participants (6.5%) in the placebo group were given epinephrine for grade 1 or 2 reactions; of these, the majority (92.7%) was treated with a single dose of epinephrine.Overall, 67% of the participants 4 to 17 years old were able to tolerate 600 mg of peanut protein (2 kernels) during the exit food challenge.These data are important, and AR101 will give health care providers a standardized way forward to treat this potentially life-threatening condition. It is hopeful that the product will be US Food and Drug Administration approved by the time this synopsis is published.

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.

Sustained outcomes in oral immunotherapy for peanut allergy (POISED study): a large, randomised, double-blind, placebo-controlled, phase 2 study

Dietary avoidance is recommended for peanut allergies. We evaluated the sustained effects of peanut allergy oral immunotherapy (OIT) in a randomised long-term study in adults and children. In this randomised, double-blind, placebo-controlled, phase 2 study, we enrolled participants at the Sean N Parker Center for Allergy and Asthma Research at Stanford University (Stanford, CA, USA) with peanut allergy aged 7-55 years with a positive result from a double-blind, placebo-controlled, food challenge (DBPCFC; ≤500 mg of peanut protein), a positive skin-prick test (SPT) result (≥5 mm wheal diameter above the negative control), and peanut-specific immunoglobulin (Ig)E concentration of more than 4 kU/L. Participants were randomly assigned (2·4:1·4:1) in a two-by-two block design via a computerised system to be built up and maintained on 4000 mg peanut protein through to week 104 then discontinued on peanut (peanut-0 group), to be built up and maintained on 4000 mg peanut protein through to week 104 then to ingest 300 mg peanut protein daily (peanut-300 group) for 52 weeks, or to receive oat flour (placebo group). DBPCFCs to 4000 mg peanut protein were done at baseline and weeks 104, 117, 130, 143, and 156. The pharmacist assigned treatment on the basis of a randomised computer list. Peanut or placebo (oat) flour was administered orally and participants and the study team were masked throughout by use of oat flour that was similar in look and feel to the peanut flour and nose clips, as tolerated, to mask taste. The statistician was also masked. The primary endpoint was the proportion of participants who passed DBPCFCs to a cumulative dose of 4000 mg at both 104 and 117 weeks. The primary efficacy analysis was done in the intention-to-treat population. Safety was assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02103270. Between April 15, 2014, and March 2, 2016, of 152 individuals assessed, we enrolled 120 participants, who were randomly assigned to the peanut-0 (n=60), peanut-300 (n=35), and placebo groups (n=25). 21 (35%) of peanut-0 group participants and one (4%) placebo group participant passed the 4000 mg challenge at both 104 and 117 weeks (odds ratio [OR] 12·7, 95% CI 1·8-554·8; p=0·0024). Over the entire study, the most common adverse events were mild gastrointestinal symptoms, which were seen in 90 of 120 patients (50/60 in the peanut-0 group, 29/35 in the peanut-300 group, and 11/25 in the placebo group) and skin disorders, which were seen in 50/120 patients (26/60 in the peanut-0 group, 15/35 in the peanut-300 group, and 9/25 in the placebo group). Adverse events decreased over time in all groups. Two participants in the peanut groups had serious adverse events during the 3-year study. In the peanut-0 group, in which eight (13%) of 60 participants passed DBPCFCs at week 156, higher baseline peanut-specific IgG4 to IgE ratio and lower Ara h 2 IgE and basophil activation responses were associated with sustained unresponsiveness. No treatment-related deaths occurred. Our study suggests that peanut OIT could desensitise individuals with peanut allergy to 4000 mg peanut protein but discontinuation, or even reduction to 300 mg daily, could increase the likelihood of regaining clinical reactivity to peanut. Since baseline blood tests correlated with week 117 treatment outcomes, this study might aid in optimal patient selection for this therapy. National Institute of Allergy and Infectious Diseases.

Oral Immunotherapy for Peanut Allergy: It Works, But...

Research Article| August 01 2019 Oral Immunotherapy for Peanut Allergy: It Works, But... AAP Grand Rounds (2019) 42 (2): 20. https://doi.org/10.1542/gr.42-2-20 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Oral Immunotherapy for Peanut Allergy: It Works, But.... AAP Grand Rounds August 2019; 42 (2): 20. https://doi.org/10.1542/gr.42-2-20 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: immunotherapy, peanut hypersensitivity, adverse event Source: Chu DK, Wood RA, French S, et al. Oral immunotherapy for peanut allergy (PACE): a systematic review and meta-analysis of efficacy and safety. Lancet. 2019; 393(10187): 2222– 2232; doi: https://doi.org/10.1016/S0140-6736(19)30420-9Google Scholar Investigators from multiple institutions conducted a meta-analysis to assess the safety and efficacy of oral immunotherapy for peanut allergy. Investigators searched MEDLINE, Embase, the Cochrane Controlled Register of Trials, and databases at the US Food and Drug Administration and European Medicines Agency from inception to 2018 to identify published and unpublished randomized controlled trials (RCTs) comparing oral immunotherapy with placebo or allergen avoidance for the treatment of peanut allergy. The investigators pooled data among included studies for several outcomes, including (a) peanut-induced anaphylaxis, defined as involvement of ≥2 organ systems after possible allergen exposure; (b) epinephrine use; (c) serious adverse events; and (d) proportion of patients who passed a supervised in-clinic oral food challenge. The investigators analyzed these outcomes according to intention to treat. Risk ratios or incidence rate ratios for these outcomes among participants receiving oral immunotherapy (vs placebo or allergen avoidance) were determined. Among 1,624 records identified, 12 RCTs were included involving 1,041 participants with a median age of 8.7 years. In all trials, peanut oral immunotherapy involved defatted peanut flour, paste, or extract. Patients who received oral immunotherapy (vs no immunotherapy) had a significantly increased likelihood of passing a supervised in-clinic oral challenge (risk ratio [RR], 12.42; 95% CI, 6.82–22.61). However, compared to those who received no immunotherapy, participants who received oral immunotherapy had a significantly greater risk of anaphylaxis (RR, 3.12; 95% CI, 1.76–5.55), epinephrine use (RR, 2.21; 95% CI, 1.27–3.83), and serious adverse events (RR, 1.92; 95% CI, 1.00–3.66). The investigators conclude that although oral immunotherapy effectively induces desensitization, it comes at considerable expense, with increased serious adverse events and anaphylactic reactions. Dr Rosenthal has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. Peanut allergy can be life-threatening. Desensitization with trace amounts of peanut protein gradually increased over time can be used to overcome lifelong avoidance of peanuts.1 This method has an efficacy of 67.2%, but how safe is this approach? (See AAP Grand Rounds. 2019;4[3]:32.1 ) The current study reports on a meta-analysis of the safety and efficacy of oral immunotherapy for peanut allergy. Compared to those who received no immunotherapy, children who received oral peanut immunotherapy had a significantly increased risk of anaphylaxis, epinephrine use, and serious adverse events. What can be done to avoid these serious adverse events? Do not forget that prevention of peanut allergy can be achieved with early introduction of peanut protein in children. (See AAP Grand Rounds. 2015;33[6]:61.2 ) The Learning Early About Peanut Allergy (LEAP) study tested the theory that the very low rates of peanut allergy in Israeli children were a result of... You do not currently have access to this content.

Oral immunotherapy for peanut allergy (PACE): a systematic review and meta-analysis of efficacy and safety

Oral immunotherapy is an emerging experimental treatment for peanut allergy, but its benefits and harms are unclear. We systematically reviewed the efficacy and safety of oral immunotherapy versus allergen avoidance or placebo (no oral immunotherapy) for peanut allergy. In the Peanut Allergen immunotherapy, Clarifying the Evidence (PACE) systematic review and meta-analysis, we searched MEDLINE, EMBASE, Cochrane Controlled Register of Trials, Latin American & Caribbean Health Sciences Literature, China National Knowledge Infrastructure, WHO's Clinical Trials Registry Platform, US Food and Drug Administration, and European Medicines Agency databases from inception to Dec 6, 2018, for randomised controlled trials comparing oral immunotherapy versus no oral immunotherapy for peanut allergy, without language restrictions. We screened studies, extracted data, and assessed risk of bias independently in duplicate. Main outcomes included anaphylaxis, allergic or adverse reactions, epinephrine use, and quality of life, meta-analysed by random effects. We assessed certainty (quality) of evidence by the GRADE approach. This study is registered with PROSPERO, number CRD42019117930. 12 trials (n=1041; median age across trials 8·7 years [IQR 5·9-11·2]) showed that oral immunotherapy versus no oral immunotherapy increased anaphylaxis risk (risk ratio [RR] 3·12 [95% CI 1·76-5·55], I2=0%, risk difference [RD] 15·1%, high-certainty), anaphylaxis frequency (incidence rate ratio [IRR] 2·72 [1·57-4·72], I2=0%, RD 12·2%, high-certainty), and epinephrine use (RR 2·21 [1·27-3·83], I2=0%, RD 4·5%, high-certainty) similarly during build-up and maintenance (pinteraction=0·92). Oral immunotherapy increased serious adverse events (RR 1·92 [1·00-3·66], I2=0%, RD 5·7%, moderate-certainty), and non-anaphylactic reactions (vomiting: RR 1·79 [95%CI 1·35-2·38], I2=0%, high-certainty; angioedema: 2·25 [1·13-4·47], I2=0%, high-certainty; upper tract respiratory reactions: 1·36 [1·02-1·81], I2=0%, moderate-certainty; lower tract respiratory reactions: 1·55 [0·96-2·50], I2=28%, moderate-certainty). Passing a supervised challenge, a surrogate for preventing out-of-clinic reactions, was more likely with oral immunotherapy (RR 12·42 [95% CI 6·82-22·61], I2=0%, RD 36·5%, high-certainty). Quality of life was not different between groups (combined parents and self report RR 1·21 [0·87-1·69], I2=0%, RD 0·03%, low-certainty). Findings were robust to IRR, trial sequential, subgroup, and sensitivity analyses. In patients with peanut allergy, high-certainty evidence shows that available peanut oral immunotherapy regimens considerably increase allergic and anaphylactic reactions over avoidance or placebo, despite effectively inducing desensitisation. Safer peanut allergy treatment approaches and rigorous randomised controlled trials that evaluate patient-important outcomes are needed. None.