Oral immunotherapy may improve peanut tolerance in children, adolescents with allergy
Children and adolescents with severe peanut allergy treated with the peanut-derived oral biologic immunotherapy drug AR101 may improve their tolerance to peanut protein with reduced symptom severity, according to the phase III PALISADE* trial.
“[The] data show that … among participants 4 to 17 years of age, AR101 had immunomodulatory activity, raised the threshold dose of peanut exposure triggering the onset of clinically significant allergic symptoms [among participants having symptoms] during the … exit food challenge, and attenuated the severity of those symptoms when they occurred,” said the researchers.
Participants were 551 individuals aged 4–55 years with peanut allergy (serum peanut-specific IgE ≥0.35 kUA/L and/or mean wheal diameter ≥3 mm larger than control on skin-prick test) from North America and Europe, who, following an allergic reaction during the double-blind, placebo-controlled challenge exposure to ≤100 mg peanut protein, were randomized to receive AR101 in a dose-escalation manner or placebo.
Patients who completed the regimen (AR101 300 mg/day for 24 weeks) underwent an end-of-trial food challenge with exposure to 300, 600, and 1,000 mg peanut protein as tolerated. The primary efficacy population comprised 496 patients aged 4–17 years; 372 and 124 received AR101 and placebo, respectively.
At the end-of-trial food challenge, more patients who had received AR101 could tolerate the single challenge dose of ≥600 mg of peanut protein (approximately two peanut kernels) without exhibiting dose-limiting symptoms (67.2 percent vs 4.0 percent, difference, 63.2 percentage points, 95 percent confidence interval, 53.0–73.3; p<0.001). [N Engl J Med 2018;379:1991-2001]
More AR101 than placebo recipients could tolerate doses of 1,000 mg (approximately 3–4 peanut kernels) during the end-of-trial challenge (50.3 percent vs 2.4 percent; p<0.001).
During the end-of-trial challenge, 25 and 59 percent of patients who received AR101 and placebo, respectively, experienced moderate symptoms, while 5 and 11 percent, respectively, experienced severe symptoms (p<0.001 for both between-group differences). Ten percent of AR101 recipients required rescue epinephrine during the end-of-trial challenge compared with 53 percent of placebo recipients.
More than 95 percent of the primary population experienced adverse events (AEs) during the study; 34.7 and 50.0 percent of AR101 and placebo recipients, respectively, experienced mild AEs. AEs that occurred more frequently among AR101 than placebo recipients were events affecting the gastrointestinal tract (85.8 percent vs 69.4 percent), respiratory tract (81.2 percent vs 71.8 percent), skin (66.9 percent vs 55.6 percent), and immune system (16.9 percent vs 8.9 percent).
Exposure-adjusted serious or severe AE rates were 5.6 and 1.6 percent of AR101 and placebo recipients, respectively.
Due to the lack of approved treatments for peanut allergy, patients require a “strict elimination diet” and “timely administration of rescue medications” if reactions or accidental exposure occur, said the researchers. “However, despite vigilance, accidental exposures may occur and cause reactions of unpredictable severity, even with small amounts of allergen, leading to a lifelong risk of severe reactions.”
“Our hope when we started the study was that by treating patients with the equivalent of one peanut per day, many would tolerate as much as two peanuts. We were pleased to find that two thirds of the people in the study were able to tolerate the equivalent of two peanuts per day after nine to 12 months of treatment, and half the patients tolerated the equivalent of four peanuts,” said study author Dr Stephen Tilles, a consulting advisor for Aimmune Therapeutics.
“We’re excited about the potential to help children and adolescents with peanut allergy protect themselves against accidentally eating a food with peanut in it,” he said.
As these results were based on a 6-month maintenance regimen, the long-term safety and efficacy of AR101 needs investigating, the researchers said.
“The major concern regarding immunotherapy is that the allergen tolerance that is induced will be temporary and lost if regular consumption ceases,” said Dr Michael Perkin from the University of London, London, UK, in an editorial. [N Engl J Med 2018;379:2074-2075]
“[S]ustained, potentially lifelong, regular consumption may be needed to maintain allergen tolerance,” he said.