Oral immunotherapy may lead to remission of peanut allergy in young children
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Oral immunotherapy was associated with an increase in both desensitization and remission of peanut allergy among children aged younger than 4 years, with younger children seeing greater success, according to data published in The Lancet.
“The results are significant in that it is the first blinded study of oral immunotherapy (OIT) focused on this toddler age group,” author Edwin H. Kim, MD, MS, associate professor of pediatrics and medicine and division chief of UNC Pediatric Allergy & Immunology at University of North Carolina School of Medicine, told Healio.
“With folks introducing peanut earlier and earlier based on the LEAP guidelines, we are anticipating much more awareness and diagnosis of peanut allergy at very young ages,” Kim added.
In a press release from the NIH, which funded the clinical trial, Anthony S. Fauci, MD, director of the NIH’s National Institute of Allergy and Infectious Diseases, said the study’s “landmark results” indicate an opportunity for OIT to induce remission of peanut allergy in early childhood.
“It is our hope that these study findings will inform the development of treatment modalities that reduce the burden of peanut allergy in children,” Fauci said.
The multicenter double-blind study included 146 children aged 12 to 48 months (median age, 39.3 months; 68% boys) who could tolerate an average of 25 mg of peanut protein.
After skin prick testing, double-blind placebo-controlled food challenges (DBPCFCs) and immune assays confirmed peanut allergy, researchers randomly assigned children to peanut OIT (n = 96) or placebo (n = 50).
Participants received lightly roasted, partly defatted (12% fat) peanut flour or oat flour.
Daily doses increased from 0.1 mg to 2,000 mg, or approximately six peanuts, from week 0 to about week 30. Maintenance with 2,000 mg daily doses followed from weeks 30 to 134. OIT then was halted from weeks 134 to 160. Participants were instructed to avoid all other peanut consumption during the study period.
At week 134, 68 (71%; 95% CI, 61-80) participants in the peanut OIT group tolerated a 5,000 mg cumulative dose of peanut protein and achieved the primary outcome of desensitization, compared with one (2%; 95% CI, 0.05-11) in the placebo group (risk difference, 69%; 95% CI, 59-79; P < .0001).
At week 160, 20 (21%; 95% CI, 13-30) participants in the peanut OIT group and one (2%; 95% CI, 0.05-11) in the placebo group (risk difference, 19%; 95% CI, 10-28; P = .0021) passed a 5,000 mg DBPCFC (approximately 16 peanuts), achieving remission, which served as the other primary outcome.
Results varied by age. In the peanut OIT group, researchers reported remission in five (71%) of the seven children aged 12 to 23.9 months, seven (35%) of the 20 children aged 24 to 35.9 months and eight (19%) of the 43 children aged 36 to 47.9 months (P = .013).
“It doesn’t look like any of this is naturally outgrowing the allergy because only one of the kids on placebo could eat the 5,000 mg without symptoms over the same time period,” Kim said.
All participants who achieved remission then took part in an 8,000 mg open-label peanut butter feeding, with 17 (85%) of the 20 peanut OIT patients and the one who received placebo passing the test.
Also, 20 children who did not achieve remission could still tolerate between 1,755 mg and 3,755 mg at 160 weeks. Overall, then, 40 of 70 children (57%) who completed treatment could safely consume approximately 6 to 12 peanuts, compared with one of 23 (4%) in the placebo group.
“We think most allergic reactions happen with exposure to less than one peanut. With this in mind, over 80% (58 out of 70) were able to eat almost three peanuts without symptoms after stopping for 6 months,” Kim said.
Dosing reactions occurred among 94 (98%) of the peanut OIT participants and 40 (80%) of the placebo participants. The most frequent reactions included mild or moderate skin, gastrointestinal and respiratory disorders.
Five of the peanut OIT participants experienced severe symptoms during at-home dosing, and one participant in the placebo group experienced a serious adverse event during a DBPCFC in week 134.
“The findings show that, first of all, OIT is feasible in this young group and at least as safe if not safer than seen in the older kids in the pivotal PALISADE study,” Kim said. “Second, as we had hoped and hypothesized, it seems the OIT has a stronger effect in this younger group compared with the older kids.”
Noting that the FDA ultimately will decide if and when clinics will be able to treat children in this age group with peanut OIT, Kim said that doctors can begin educating patients and preparing clinics to provide this care.
Because age and remission outcome appeared inversely associated, the researchers said that an “enhanced window for remission” may close early, and further studies of age-defined risks and benefits of peanut OIT are warranted. The researchers plan to continue their work in three stages.
First, a practical, larger, multicenter study will attempt to ensure the safety of the treatment in this age group to bring it to a clinic, Kim said.
“Second would be a deep dive into the immunology of this age group to understand who is likely to respond to treatment, who is likely to get remission and finding ways that we can amplify these results,” he continued. “Third would be moving beyond peanut and addressing other common food allergies such as milk, egg and tree nuts to see how they are similar and how they are unique with regards to treatment.”
In an accompanying editorial, Matthew Greenhawt, MD, of Children’s Hospital Colorado, and colleagues wrote that results of this study suggest early childhood peanut OIT is “ready for immediate real-world implementation.”
“Although additional trials might enhance the certainty of evidence for OIT in these ages, further delay in implementing OIT risks withholding proven benefit,” they wrote. “Waiting for regulatory approval for commercial products for very young children for this treatment to be deemed ready does not benefit families.”
For more information:
Edwin H. Kim, MD, MS, can be reached at edwinkim@email.unc.edu.
References:
- Greenhawt M, et al. Lancet. 2022;doi:10.1016/S0140-6736(22)00088-5.
- Initiating peanut oral immunotherapy in peanut-allergic children under age four may be more effective, first long term study suggests. https://www.eurekalert.org/news-releases/940531. Published Jan. 20, 2022. Accessed Jan. 20, 2022.
- Oral immunotherapy induces remission of peanut allergy in some young children. https://www.nih.gov/news-events/news-releases/oral-immunotherapy-induces-remission-peanut-allergy-some-young-children. Published Jan. 20, 2022. Accessed Jan. 20, 2022.
Perspective
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I'm very glad to see this study conducted in such a rigorous manner. It offers tremendous insight into furthering our understanding of starting OIT in younger age groups.
I'm not that surprised at the results, as they seem to confirm what we know from OIT in older children with variable responses to treatment, risk for reactions with treatment and a shift in immune response for those who can tolerate higher amounts through treatment.
We have held off on starting OIT in younger children for various reasons, particularly a paucity of data to help guide our way. But it's exciting to see further research in this area.
Most importantly, I think this study emphasizes that OIT absolutely requires shared decision-making to ensure families truly understand risks, benefits and expected outcomes. This process requires supervision and availability from the treating provider to answer questions and help families navigate some of the challenges involved.
I do not believe this trial should be used as a “green light” to start OIT for peanut in all infants or toddlers. But it does pave the way to have that conversation with families about risks and benefits. Also, OIT should never be done without following specific protocols and supervision from an experienced allergist or specialist in this area.
Unfortunately, there was only a relatively small number of children included in this study who were aged younger than 2 years, so it would be very helpful to see larger studies in this age group.
Ongoing research in this area is valuable to try and identify some predictive factors for those children who can achieve long-term sustained unresponsiveness, as well as those at risk for bad outcomes.
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