DEVIL: First Results Support Low-Dose Peanut Immunotherapy

SAN ANTONIO, Texas — Introducing a low-dose form of oral peanut immunotherapy to very young children might nip the allergic process in the bud, with few adverse effects.

This finding comes from an interim analysis presented here at the American Academy of Allergy, Asthma & Immunology 2013 Annual Meeting.

"There are reasons to believe that young children may be more ideal candidates for treatment with immunotherapy," lead investigator Brian Vickery, MD, from the University of North Carolina at Chapel Hill, told reporters at a news conference.

"This study suggests that low-dose therapy appears to change the immune response to peanut to roughly the same degree as high-dose therapy," Dr. Vickery said.

The double-blind randomized trial, known as DEVIL, comparing low- and high-dose peanut immunotherapy, is ongoing. These interim results remain blinded.

"We do not know — and will not know — the treatment assignment of any of the subjects until the study is completely finished," Dr. Vickery told Medscape Medical News. However, blinded immunologic data from both treatment groups have been analyzed. "This suggests, but does not prove, that the low dose will be as effective clinically as the high dose."

Effective Low Dose

Dr. Vickery and colleagues hypothesized that early intervention with immunotherapy could disrupt the body's still-immature allergic response, encouraging sensitization with a lower doses than is needed later on. If this is the case, "we will likely improve the safety profile and make it easier for children to take," Dr. Vickery said.

During his presentation, Dr. Vickery explained that "these data suggest this approach is at least as safe as, if not safer than, the studies we have done in older children."

So far, the ongoing trial has enrolled 49 children (aged 9 to 36 months): 15 sensitized children with peanut-specific immunoglobulin (Ig)E (>5 KU/L) but no known history of oral exposure; and 34 clinically allergic children within 6 months of their index reaction. These groups are "both firsts for our institution," Dr. Vickery said.

After confirmation of peanut allergy with an oral food challenge, the children were randomized to either low-dose (300 mg) or high-dose (3000 mg) oral immunotherapy with peanut protein for a minimum of 12 months.

The primary study end point is clinical tolerance, defined as the ability to ingest 5 g of peanut protein during a food challenge 4 weeks after stopping therapy.

The interim analysis shows that 12 children have completed therapy and passed the final oral food challenge, meeting criteria for clinical tolerance.

Clinical Tolerance

It is too early to draw many conclusions from this result, said Dr. Vickery, although it does show that "a 10-fold lower dose of peanut protein is capable of changing the immune response."

Low-dose immunotherapy is an immunomodulatory therapy that has an effect on mast cells and IgE approximately equivalent to that of high-dose therapy, Dr. Vickery pointed out. However, IgG4 production in this context appears to be dose-dependent.

This is some of the most exciting work we have in the field.

Despite this early suggestion of equivalent efficacy with lower dosing, there is one important caveat about the immunologic characteristics of responders, Dr. Vickery noted. At baseline, all responders were below the median for skin prick test reactions and IgE levels, "suggesting that these children essentially had a mild phenotype characterized by weaker allergic priming, so I wouldn't get too excited about these data just yet," he said.

However, session moderator Stacie Jones, MD, from the Arkansas Children's Hospital in Little Rock, insists that the results are still noteworthy.

"This is a very well-defined, very young population of kids who responded to low-dose immunotherapy.... It is incredibly exciting that they could achieve those results with a low dose," Dr. Jones said.

A therapy that requires children to ingest large amounts of allergenic material on a daily basis is often poorly tolerated, Dr. Vickery noted. Worldwide, almost one third of pediatric immunotherapy patients drop out of research trials because of adverse effects. "If we could treat with a lower dose, that would be an advance."

Dr. Jones told Medscape Medical News that "this is some of the most exciting work we have in the field. If we catch these children early, we might be able to change them immunologically enough before things get locked in."

The investigators and Dr. Jones have disclosed no relevant financial relationships.

American Academy of Allergy, Asthma & Immunology (AAAAI) 2013 Annual Meeting: Abstract 470. Presented February 24, 2013.