Children can achieve clinical remission of peanut allergy with oral immunotherapy

Oral immunotherapy with or without probiotic adjuvants conferred sustained unresponsiveness to peanut among allergic children, according to a randomized phase 2b study published in The Lancet Child & Adolescent Health.

Although the probiotic adjuvant did not improve remission rates, it may improve the safety and tolerability of OIT, research found.

“It is the first randomized controlled study of peanut oral immunotherapy to show high rates of sustained responsiveness in school-aged children and the first to show that a peanut allergy treatment can provide substantial improvement in quality of life compared to current standard of care of peanut avoidance,” author Mimi L.K. Tang, MBBS, PhD, FRACP, FRCPA, FAAAAI, CEO of Prota Therapeutics and professor at Murdoch Children’s Research Institute in Melbourne, Australia, said in a press release.

The study’s rollout

The 4-year study involved children aged 1 to 10 years with confirmed peanut allergies, with 79 participants assigned a probiotic and PRT120 (Prota Therapeutics) peanut oral immunotherapy (PPOIT), 83 participants assigned a placebo probiotic and peanut OIT, and 39 participants assigned placebo probiotic and placebo peanut OIT at three hospitals in Australia.

On day 1, participants received 2 x 10¹⁰ colony-forming units of Lactobacillus rhamnosus ATCC 53103 probiotic or placebo before receiving increasing doses of peanut protein or placebo every 20 minutes until they reached a dose of 12 mg, with a cumulative total of 24 mg.

The build-up phase began the next day in the hospital under medical supervision, with dose increases every 2 weeks until reaching the 2,000 mg maintenance dose, which was administered at home for 18 months of treatment. Participants received the probiotic or placebo probiotic depending on their cohort throughout the study period as well.

Participants then completed a double-blind, placebo-controlled food challenge with a total of 4,950 mg of peanut protein. Those who passed maintained strict peanut avoidance for 8 weeks before completing another double-blind, placebo-controlled food challenge.

Participants with sustained unresponsiveness were advised they could freely incorporate peanut into their diet, whereas desensitized participants who did not show sustained unresponsiveness were instructed to continue taking one to two peanuts a day. Allergic participants continued strict peanut avoidance.

Additionally, parents and guardians completed the Food Allergy Quality of Life Questionnaire-Parent Form to help determine health-related quality of life (HRQOL) at baseline, treatment completion and 12 months after treatment completion.

The study’s results

Forty-six percent of participants in the PPOIT group achieved sustained unresponsiveness, which did not significantly differ from the 51% rate observed in the OIT-alone group. A significantly greater proportion of both OIT groups achieved sustained unresponsiveness compared with the placebo group (5%; P < .0001 for both).

Higher rates of sustained unresponsiveness occurred among children aged 1 to 5 years than among children aged 6 to 10 years (PPOIT, 61% vs. 29%; OIT, 56% vs. 45%).

The median cumulative tolerated dose during the end-of-treatment food challenge was 4,950 mg (interquartile range [IQR], 4,950-4,950) in the PPOIT and OIT groups and 240 mg (IQR, 80-560) in the placebo group (P < .0001 for both).

Also, 72 participants (91%) in the PPOIT group, 73 (88%) in the OIT group and 28 (72%) in the placebo group reported treatment-related adverse events, with abdominal pain frequently reported across all groups. However, researchers observed a significant reduction in exposure-adjusted incidence of abdominal pain, vomiting and system organ class respiratory disorders in the PPOIT vs. OIT group.

During the 12 months after treatment, 85% participants in the PPOIT group, 86% in the OIT group and 18% in the placebo group were eating peanut.

Also, 99% of the participants with sustained unresponsiveness were eating peanut according to their own preferences, with a median amount of 0.6 g to 2 g of peanut protein (three to 10 peanuts) at a median frequency of one to two times a week. Meanwhile, 93% of desensitized participants and 13% of allergic participants were eating peanut.

Participants in the PPOIT and OIT groups reported clinically and statistically significant improvements in HRQOL during the 12 months following treatment compared with the placebo group, even though the active treatment groups saw higher rates of adverse events.

The participants who achieved sustained unresponsiveness saw improvements across all subscales, the researchers wrote, with the greatest improvements in social and dietary limitations. They also reported significantly fewer peanut reactions and two times less rescue epinephrine use than participants in the desensitization group.

This suggests that the ability to freely eat peanut provides greater benefits than continued allergen avoidance, even though reactions are more likely, the researchers wrote.

The researchers concluded that the probiotic adjuvant did not improve the efficacy of OIT based on measures of sustained unresponsiveness or desensitization, nor did it improve immunological parameters such as peanut skin-prick tests or peanut-specific IgE or IgG₄.

However, they continued, the probiotic adjuvant may provide meaningful safety benefits, considering the burden of gastrointestinal symptoms and systemic reactions, particularly among children aged 1 to 5 years.

Reference:

• Prota Therapeutics achieves peanut allergy treatment milestone: Groundbreaking clinical trial data demonstrates clinical remission of peanut allergy in paediatric patients. https://www.prnewswire.com/news-releases/prota-therapeutics-achieves-peanut-allergy-treatment-milestone-groundbreaking-clinical-trial-data-demonstrates-clinical-remission-of-peanut-allergy-in-paediatric-patients-301478382.html. Posted Feb. 9, 2022. Accessed Feb. 9, 2022.