Efficacy and safety of oral immunotherapy in children aged 1–3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study

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Background

For young children with peanut allergy, dietary avoidance is the current standard
of care. We aimed to assess whether peanut oral immunotherapy can induce desensitisation
(an increased allergic reaction threshold while on therapy) or remission (a state
of non-responsiveness after discontinuation of immunotherapy) in this population.

Methods

We did a randomised, double-blind, placebo-controlled study in five US academic medical
centres. Eligible participants were children aged 12 to younger than 48 months who
were reactive to 500 mg or less of peanut protein during a double-blind, placebo-controlled
food challenge (DBPCFC). Participants were randomly assigned by use of a computer,
in a 2:1 allocation ratio, to receive peanut oral immunotherapy or placebo for 134
weeks (2000 mg peanut protein per day) followed by 26 weeks of avoidance, with participants
and study staff and investigators masked to group treatment assignment. The primary
outcome was desensitisation at the end of treatment (week 134), and remission after
avoidance (week 160), as the key secondary outcome, were assessed by DBPCFC to 5000
mg in the intention-to-treat population. Safety and immunological parameters were
assessed in the same population. This trial is registered on ClinicalTrials.gov, NCT03345160.

Findings

Between Aug 13, 2013, and Oct 1, 2015, 146 children, with a median age of 39·3 months
(IQR 30·8–44·7), were randomly assigned to receive peanut oral immunotherapy (96 participants)
or placebo (50 participants). At week 134, 68 (71%, 95% CI 61–80) of 96 participants
who received peanut oral immunotherapy compared with one (2%, 0·05–11) of 50 who received
placebo met the primary outcome of desensitisation (risk difference [RD] 69%, 95%
CI 59–79; p<0·0001). The median cumulative tolerated dose during the week 134 DBPCFC
was 5005 mg (IQR 3755–5005) for peanut oral immunotherapy versus 5 mg (0–105) for
placebo (p<0·0001). After avoidance, 20 (21%, 95% CI 13–30) of 96 participants receiving
peanut oral immunotherapy compared with one (2%, 0·05–11) of 50 receiving placebo
met remission criteria (RD 19%, 95% CI 10–28; p=0·0021). The median cumulative tolerated
dose during the week 160 DBPCFC was 755 mg (IQR 0–2755) for peanut oral immunotherapy
and 0 mg (0–55) for placebo (p<0·0001). A significant proportion of participants receiving
peanut oral immunotherapy who passed the 5000 mg DBPCFC at week 134 could no longer
tolerate 5000 mg at week 160 (p<0·001). The participant receiving placebo who was
desensitised at week 134 also achieved remission at week 160. Compared with placebo,
peanut oral immunotherapy decreased peanut-specific and Ara h2-specific IgE, skin
prick test, and basophil activation, and increased peanut-specific and Ara h2-specific
IgG4 at weeks 134 and 160. By use of multivariable regression analysis of participants
receiving peanut oral immunotherapy, younger age and lower baseline peanut-specific
IgE was predictive of remission. Most participants (98% with peanut oral immunotherapy
vs 80% with placebo) had at least one oral immunotherapy dosing reaction, predominantly
mild to moderate and occurring more frequently in participants receiving peanut oral
immunotherapy. 35 oral immunotherapy dosing events with moderate symptoms were treated
with epinephrine in 21 participants receiving peanut oral immunotherapy.

Interpretation

In children with a peanut allergy, initiation of peanut oral immunotherapy before
age 4 years was associated with an increase in both desensitisation and remission.
Development of remission correlated with immunological biomarkers. The outcomes suggest
a window of opportunity at a young age for intervention to induce remission of peanut
allergy.

Funding

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



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