Academic journal

Efficacy and Safety of Oral Immunotherapy in Children Aged 1-3 Years with Peanut Allergy (Immune Tolerance Network IMPACT Trial): A Randomized Placebo-Controlled Study

Fund

For young children with peanut allergy, food avoidance is the current standard of care. We sought to assess whether oral peanut immunotherapy can induce desensitization (an increased allergic reaction threshold during treatment) or remission (a state of unresponsiveness after stopping immunotherapy) in this population.

Methods

We conducted a randomized, double-blind, placebo-controlled study at five US academic medical centers. Eligible participants were children aged 12 to less than 48 months who responded to 500 mg or less of peanut protein in a double-blind, placebo-controlled food challenge (DBPCFC). Participants were randomly assigned using a computer, in an allocation ratio of 2:1, to receive oral peanut immunotherapy or placebo for 134 weeks (2000 mg peanut protein daily ) followed by 26 weeks of avoidance, with participants and study staff and investigators masked to group treatment assignment. The primary endpoint was desensitization at the end of treatment (week 134) and remission after avoidance (week 160), as a key secondary endpoint, was assessed by the DBPCFC at 5000 mg in the intent-to-treat population. Safety and immunological parameters were evaluated in the same population. This trial is registered with ClinicalTrials.gov, NCT03345160.

Results

Between August 13, 2013 and October 1, 2015, 146 children, with a median age of 39 3 months (IQR 30 8–44 7), were randomized to receive oral peanut immunotherapy (96 participants) or a placebo (50 participants). At week 134, 68 (71%, 95% CI 61-80) of 96 participants who received oral peanut immunotherapy versus one (2%, 0 05-11) of 50 who received placebo have reached the primary endpoint of desensitization (risk difference [RD] 69%, 95% CI 59–79; pvs. 80% with placebo) had at least one reaction to oral immunotherapy dosage, mostly mild to moderate and occurring more frequently in participants receiving oral peanut immunotherapy. 35 oral immunotherapy dosing events with moderate symptoms were treated with epinephrine in 21 participants receiving oral peanut immunotherapy.

Interpretation

In children with peanut allergy, initiation of oral peanut immunotherapy before the age of 4 years has been associated with an increase in both desensitization and remission. Development of remission correlated with immunological biomarkers. The results suggest a window of opportunity at an early age for an intervention to induce peanut allergy remission.

Funding

National Institute of Allergy and Infectious Diseases, Immune Tolerance Network.