Peanut OIT appears safe across trials with different eligibility requirements

Key takeaways:

• Routine clinical practice for peanut allergy does not always include food challenges to confirm diagnosis or determine candidacy for treatment.
• A pair of trials that did not use double-blind, placebo-controlled food challenges achieved similar safety data as a pair of trials that did.
• Guidelines including high standards for peanut-specific IgE or skin prick testing may exclude patients who would otherwise benefit from peanut oral immunotherapy treatment.

Two trials that did not require oral food challenges to qualify participants for oral immunotherapy for peanut allergies achieved safety profiles that resembled those of earlier trials using these challenges, according to a study.

These safety profiles also were consistent despite differences in baseline measures between the trials, Christina Ciaccio, MD, MSc, chief of the section of pediatric allergy and immunology at The University of Chicago Medicine, and colleagues wrote in the study, published in Annals of Allergy, Asthma and Immunology.

RAMSES trial and ARC011 follow-up

The 6-month, phase 3, randomized, double-blind placebo-controlled RAMSES trial involved 506 children aged 4 to 17 years with a physician-confirmed peanut allergy who received Peanut (Arachis hypogaea) Allergen Powder-dnfp (Palforzia, Aimmune Therapeutics), also called PTAH (n = 338), or placebo (n = 186). Doses began with an initial dose escalation (IDE), followed by updosing until achieving a target dose of 300 mg for up to 40 weeks (achieved by 78.9% of the PTAH group and 94% of the placebo group).

The ARC011 study followed 243 patients through maintenance PTAH treatment for another 6 months.

The researchers did not use double-blind, placebo-controlled food challenges (DBPCFCs), which are not routinely used in clinical practice outside of specialized academic centers, to select these trial population or evaluate outcomes. Rather, participants were required to have a high pre-test probability of peanut allergy.

Median trial exposures during RAMSES included 5.59 months for the PTAH group and 5.56 months for the placebo group; 93.5% of the PTAH group who completed the trial continued in ARC011, with a median PTAH exposure of 5.63 months.

During RAMSES, 55.5% of the PTAH group and 33.9% of the placebo group experienced one or more adverse events during IDE, which increased to 98.8% of the PTAH group and 94% of the placebo group through the 6 months of updosing. Overall, adverse events caused 12.5% of the PTAH group and 2.4% of the placebo group to leave the trial.

Maximum severities of these adverse events in the PTAH group were mild (44.8%) or moderate (51%) in both trials. Specifically during RAMSES, 90.2% of the PTAH group and 58.3% of the placebo group experienced adverse events that were considered related to treatment, and these events most frequently occurred during the IDE phase.

Gastrointestinal events, more frequent during the updosing phase, accounted for the most common issues, including 87.8% of the adverse events in the PTAH group and 57.1% of the events in the placebo group in RAMSES as well as 53.7% of the events during ARC011.

Trial comparisons

Next, the researchers compared these and other findings with the results of the earlier PALISADE (PTAH, n = 372; placebo, n = 124) and ARTEMIS (PTAH, n = 132; placebo, n = 43) trials, which used DBPCFCs in evaluating the efficacy and safety of PTAH treatment, as well as in screening patients for trial participation.

Pooled data from these prior studies showed 49.8% of patients treated with PTAH experienced adverse events during the IDE phase, and 96.7% experienced them during the updosing phase, which the researchers called similar to the RAMSES study. Rates were nearly identical between these studies during the maintenance phases as well, the researchers added.

Also, participants in the RAMSES and ARC011 trials experienced an exposure-adjusted rate of 14.6 treatment-related adverse events per person-years of exposure after 6 months of maintenance treatment, which was numerically lower than the 18 events per person-years of exposure observed in the PALISADE trial.

Pooled PALISADE and ARTEMIS vs. RAMSES participants had comparable rates of treatment discontinuations (8.6% vs. 9.8%) and systemic allergic reactions (8.1% vs. 9.8%) during updosing, as well as epinephrine use after adverse events (8.1% vs. 9.8%). Also, the most common adverse events in both groups were gastrointestinal (83.3% vs. 86.2%).

However, the researchers noted that 36.7% of the participants in the PALISADE and ARTEMIS trials with baseline data on peanut-specific IgE (psIgE) or skin prick testing would not have met the more stringent psIgE and SPT entry criteria that RAMSES required.

In other words, the researchers wrote, more than one out of three patients with peanut allergies would not have been offered PTAH treatment if the indication for treatment only was based on candidates who met the eligibility criteria that PALISADE and ARTEMIS used.

Clinicians should consider the limitations of using psIgE or peanut SPT cutoffs to determine likelihood of reactions to food challenges, the researchers wrote, particularly when they are evaluating patients who may benefit from PTAH treatment.