In children with a peanut allergy, initiation of peanut oral immunotherapy before age-four was associated with an increase in both desensitisation and remission, found the IMPACT trial, published in The Lancet.
Funded by the US National Institutes of Health, the trial found the treatment desensitised most of them (71%) to peanut and induced remission of peanut allergy in one-fifth.
The immunotherapy consisted of a daily oral dose of peanut flour for 2.5 years. Remission was defined as being able to eat 5g of peanut protein, equivalent to 1.5 tablespoons of peanut butter, without having an allergic reaction six months after completing immunotherapy. The youngest children and those who started the trial with lower levels of peanut-specific antibodies were most likely to achieve remission. The results of the trial, called IMPACT, were published in The Lancet.
The NIH trial found experimental therapy also reduced most children’s sensitivity to peanuts.
“The landmark results of the IMPACT trial suggest a window of opportunity in early childhood to induce remission of peanut allergy through oral immunotherapy,” said Dr Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH. “It is our hope that these study findings will inform the development of treatment modalities that reduce the burden of peanut allergy in children.”
NIAID sponsored the trial and funded it through its Immune Tolerance Network.
Peanut allergy affects about 2% of children in the United States, or nearly 1,5m youngsters aged 17 years old and younger. The risk of a life-threatening allergic reaction to accidentally eaten peanuts is significant for these children, most of whom remain peanut-allergic for life.
When designing the study, the IMPACT trial investigators reasoned that because oral immunotherapy has the potential to change the immune system, providing peanut oral immunotherapy early in life, when the immune system is still maturing, might modify a child’s immune response to peanuts. Two previous studies provided proof of concept that peanut oral immunotherapy could be given safely to very young children and have a therapeutic effect.
Nearly 150 children ages 1 to 3 years participated in the IMPACT trial at five academic medical centres in the US. Only children who had an allergic reaction after eating half a gram of peanut protein (about 1,5 peanuts) or less were eligible to join the study. The children were assigned at random to receive either flour containing peanut protein or a placebo flour of similar appearance. The flours were mixed with foods such as applesauce or pudding to help mask their taste. No one except a site pharmacist and a site dietician knew who received peanut flour or placebo flour until all the data were gathered and study visits had ended.
During a 30-week period, the children in the treatment group ate gradually-escalating daily doses of up to 2g of peanut protein, equivalent to about six peanuts. The children then continued to consume their daily dose of peanut or placebo flour for an additional two years.
Next, the children underwent an oral food challenge in which they received gradually increasing doses of peanut protein up to a cumulative maximum of 5g. They then stopped treatment and avoided peanut for six months.
Finally, the children underwent a repeat oral food challenge with 5g of peanut protein, equivalent to about 16 peanuts. Those who did not have an allergic reaction during the challenge were later fed 8g of peanut butter, equivalent to 2 tablespoons, on a different day to confirm that they could eat peanut without having an allergic reaction.
At the end of the treatment period, 71% of children who had received peanut flour were desensitised to peanut, compared to only 2% of those who had received the placebo flour. Desensitisation was defined as being able to eat 5g of peanut protein during the first oral food challenge without having an allergic reaction. After six months of peanut avoidance following treatment, 21% of children who had received peanut flour could eat 5g of peanut protein during the second oral food challenge without having an allergic reaction and therefore were in remission. By contrast, only 2% of children who had received placebo flour were in remission at that time.
The investigators found that lower levels of peanut-specific immunoglobulin E antibodies at the start of the trial, and being younger, predicted whether a child would achieve remission. In an analysis done after the investigators could view the study data, they found an inverse relationship between age at the start of the trial and remission, with 71% of the 1-year-olds, 35% of the 2-year-olds and 19% of the 3-year-olds experiencing remission.
Although nearly all of the children who received peanut flour had at least one dose-related reaction during treatment, most reactions were mild to moderate in severity. Twenty-one children received the rescue drug epinephrine for 35 moderate reactions to peanut flour during the 2,5-year treatment period.
The Immune Tolerance Network conducted the trial under the leadership of Dr A. Wesley Burks and Dr Stacie Jones. Burks is chief executive officer of UNC Health, dean of the University of North Carolina School of Medicine, and vice chancellor for medical affairs at the University of North Carolina at Chapel Hill. Jones is a professor of paediatrics at the University of Arkansas for Medical Sciences and Arkansas Children’s Hospital in Little Rock.
Study details
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.
Stacie Jones, Edwin Kim, Kari Nadeau, Anna Nowak-Wegrzyn, Robert Wood, Hugh Sampson, Amy Scurlock, Sharon Chinthrajah, Julie Wang, Robert Pesek, Sayantani Sindher, Mike Kulis, Jacqueline Johnson, Katharine Spain, Denise Babineau, Hyunsook Chin, Joy Laurienzo-Panza, Rachel Yan, David Larson, Tielin Qin, Don Whitehouse, Michelle Sever, Srinath Sanda, Marshall Plaut, Lisa Wheatley, A Wesley Burks.
Published in The Lancet on 22 January 2022
Summary
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.
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.
IMPACT trial info available at ClinicalTrials.gov NCT01867671
The Lancet article – 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 (Open access)
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