Peanut Allergy Symptom Severity Reduced With PTAH Immunotherapy

Peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) significantly decreased symptom severity from peanut exposure, according to a study in Allergy, Asthma & Clinical Immunology.

Oral immunotherapy with PTAH has been proven effective as oral immunotherapy for those with peanut allergies in 3 advanced clinical trials, PALISADE (ClinicalTrials.gov Identifier: NCT02635776), the PALISADE follow-on (ARC004: ClinicalTrials.gov Identifier: NCT02993107), and ARTEMIS (ClinicalTrials.gov Identifier: NCT03201003). The current post hoc analysis of these 3 trials examined data from the double-blind, placebo-controlled food challenges (DBPCFCs) performed at the initial screening and exit from each of these trials to gain insight into how those treated with PTAH would react to an accidental peanut exposure.

Of the 3 trials included in the post hoc analysis, PALISADE and ARTEMIS, both phase 3 trials, had a 1000-mg maximum peanut protein dose during DBPCFCs, and the ARC004 (the PALISADE follow-on) had a maximum dose of 2000 mg. (Notably, the PALISADE trials involved adults and children, whereas the ARTEMIS trial involved children aged 4 to 17 years.) Symptoms were recorded by system organ class (SOC) and maximum severity. Study endpoints were: (1) change in peanut symptom severity; and (2) freedom from symptoms during DBPCFC, both of which were measured by comparing relative risk (RR) of the outcome (by SOC for symptom severity) for the PTAH vs control groups.

Investigators found that in the phase 3 PALISADE trial, the risk for respiratory, gastrointestinal (GI), cardiovascular/neurologic, or dermatologic symptoms was significantly reduced among individuals who received PTAH at exposure to peanut at the trial’s end. The participants who received PTAH vs placebo had a relative risk (RR) of 0.42 (95% CI, 0.30-0.60; P <.0001) for respiratory symptoms, 0.34 (95% CI, 0.26-0.44; P <.0001) for GI symptoms, 0.17 (95% CI, 0.08-0.39; P <.001) for cardiovascular/neurologic symptoms, and 0.33 (95% CI, 0.22-0.50; P <.0001) for dermatologic symptoms. Total freedom from symptoms was exhibited in the exit DBPCFC (at the reactive dose from the initial DBPCFC screening) by 76.3% of the PTAH group vs 23.4% of the placebo group.

In the PALISADE and ARTEMIS trials, a significantly higher proportion of participants who received PTAH were asymptomatic after exposure to low doses (≤100 mg) of peanut protein in the exit DBPCFC vs those who received placebo (PALISADE: 69.35% vs 12.10%, RR 5.73 [95% CI, 3.55-9.26]; P <.0001; ARTEMIS: 67.42% vs 13.95%, RR 4.83 [95% CI, 2.28-10.25]; P <.0001).

In comparing results of the PALISADE and ARTEMIS trials, the post hoc investigators found that a significantly higher proportion of individuals who were treated with PTAH for doses of 1000 mg or less completed the exit DBPCFC without any symptoms vs those who received placebo after about 6 months of PTAH maintenance in PALISADE (37.63% [n=140] vs 2.42% [n=3], RR 15.56; 95% CI, 5.05-47.94; P <.0001) and after about 3 months of PTAH maintenance in ARTEMIS (39.39% [n=52] vs 0%, RR 34.74; 95% CI, 2.19-551.03; P <.0001).

In ARC004, the PALISADE follow-on trial, a simulation of accidental exposure to peanut (peanut protein ≤1000 mg) in patients on longer maintenance treatment found the proportion of participants with no symptoms was 45.54% (n=51) after about 7 months of ongoing maintenance treatment (about 13 months total PTAH maintenance treatment) and 58.06% (n=18) after about 14 months of ongoing maintenance treatment (about 20 months total maintenance treatment).

Study limitations include the use of subjective and objective symptoms and the potential for the type of symptoms reported by participants to vary over time. Also, the analysis did not differentiate symptoms within an organ system, such as upper vs lower respiratory symptoms.

“PTAH demonstrated dose-independent and dose-dependent reduction of symptom severity after exposure to peanut,” stated the investigators. “When exposed to peanut, participants treated with PTAH rarely had moderate or severe respiratory or cardiovascular/neurologic symptoms. Oral immunotherapy with PTAH seems to reduce the risk and severity of allergic reactions after accidental exposure to peanut in individuals with peanut allergy and may enable them and their families to have an improved quality of life.”

Disclosure: This study was sponsored by Aimmune Therapeutics, a Nestlé Health Science company. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.