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.

PURPOSE: Peanut 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. METHODS: Symptom 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. RESULTS: The 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). CONCLUSIONS: PTAH 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.

A study to assess current approaches of allergists in European countries diagnosing and managing children and adolescents with peanut allergy.

RATIONALE: Food allergy is documented to result in considerable morbidity, negative impact on quality of life, and substantial medical care costs. Although anecdotal data suggest widely varying practices in the diagnosis and management of food allergies, the diversity and relative frequency of these practices have not been documented. METHODS: A questionnaire was developed evaluating allergists' management approaches of individuals with peanut allergy (PA) in Germany (DE), France (FR), and the United Kingdom (UK). RESULTS: Here, we report the survey results from a total of 109 allergists from DE, FR and the UK. They reported to confirm PA at initial diagnosis using skin prick test (≥60%), while allergists from DE and FR reported using allergen-specific IgE testing more (>86%) compared to the UK (<50%). At initial diagnosis, oral food challenge was used less in DE (13%) and FR (14%) and very rarely in the UK (3%) to confirm diagnosis. Recognition of acute reactions, use of adrenaline auto-injectors and allergen avoidance were reported to be discussed with the patient/caregiver at the initial office visit by most allergists (>75%). Half of the responders reported assessing the patient's quality of life. 63% allergists reported retesting for PA resolution at a later date, with 45% allergists indicated to recommend ingestion of a normal serving of peanut regularly upon resolution. Lack of effective PA treatment was reported to be a 'very significant' barrier for optimal PA treatment, with allergists being less than 'moderately familiar' with data from clinical trials testing new treatments options for PA. Lastly, allergists stated that the severity of patient's PA ranked as the most important factor in their decision to recommend oral immunotherapy for PA treatment. CONCLUSIONS: This survey provides essential insights into the practice of allergists and highlights some areas that would inform strategies for education and improving PA healthcare.