Kate Johnson

February 26, 2015

HOUSTON — Adding the probiotic Lactobacillus rhamnosus GG to standard peanut oral immunotherapy could boost response rates, according to results from a new study.

This is a "world-first study" of a probiotic used in combination with oral immunotherapy, said lead investigator Mimi Tang, PhD, from Royal Children's Hospital in Melbourne, Australia.

"I don't believe that immunotherapy on its own will be particularly effective for the treatment of food allergy," she told Medscape Medical News. "I think something else has to be presented with the food to help the immune system change the way it responds," she explained. "Probiotics are thought to modulate the immune response to help the immune system respond differently when presented with the allergen."

Results from the double-blind trial were presented here at the American Academy of Allergy, Asthma & Immunology 2015, and published online in the Journal of Allergy and Clinical Immunology.

Peanut-allergic children 1 to 10 years of age were randomized to either a probiotic (Lactobacillus rhamnosus GG) plus standard peanut oral immunotherapy for 18 months or a double placebo.

I think something else has to be presented with the food to help the immune system change the way it responds.

Lactobacillus rhamnosus GG was selected because it has been "very well studied and has been shown in a number of different settings to induce TH1, as well as T regulatory cytokine profiles and regulatory cells," Dr Tang explained.

The primary outcome of the study was sustained unresponsiveness 2 to 5 weeks after the discontinuation of treatment.

A double-blind placebo-controlled food challenge with peanut protein 4 g was conducted on the last day of treatment. The children who passed that challenge continued to eat a peanut-free diet for 2 to 5 more weeks, and were then rechallenged. If they passed the rechallenge, they were deemed to have achieved possible sustained unresponsiveness.

More children in the immunotherapy group than in the placebo group achieved sustained unresponsiveness (82.1% vs 3.6%; P < .001).

"This converts to a number needed to treat of 1.27. In other words, if nine children received the treatment, seven would benefit," Dr Tang reported.

Immunotherapy was associated with a marked reduction in peanut-induced skin-prick test wheal size. It was also associated with a decrease in peanut-specific immunoglobulin (Ig)E levels and an increase in peanut-specific IgG4 levels, "indicating that clinical benefit from immunotherapy was through resolution of peanut-specific IgE-mediated allergy," she explained.

The rate of study participants reporting at least one severe adverse event was similar in the immunotherapy and placebo groups (45.2% vs 32.3%). This was "unexpected," she noted. Rates in other immunotherapy studies have ranged from 63% to 93%.

Overall, there were more severe adverse events in the immunotherapy group than in the placebo group (34 vs 15), but one child in the immunotherapy group experienced 13 severe adverse events, she said.

"The majority of adverse events in the placebo group involved subjective abdominal pain or an asthma exacerbation," said Dr Tang. "The distribution of adverse events was quite different in the active group; the most common presenting problems were skin complaints and airway complaints, which are much more suggestive of true allergic reactions."

"This suggested to us that anxiety during the treatment phase may actually result in some nonspecific complaints that are recorded as adverse events," she said.

Future work is required to determine whether the sustained unresponsiveness will last over the long term, and to tease out the relative contributions of the probiotic and the oral immunotherapy.

This study "shows proof of concept and safety," said session moderator Amy Scurlock, MD, from Arkansas Children's Hospital in Little Rock. "The success rates were higher than some other reports, but it's hard to know if that's related to the probiotic."

A head-to-head study comparing peanut-specific immunotherapy with immunotherapy plus a probiotic is needed, she told Medscape Medical News.

However, there is evidence to suggest a synergistic effect of the probiotic. There are studies showing that Lactobacillus rhamnosus GG "increases T-helper type 1 immunity and enhances T regs, which have beneficial immune effects. With all the focus on the microbiome and probiotics, I think it's a logical next step to try this," Dr Scurlock said.

The study was supported by the Food Allergy and Anaphylaxis Network; the Murdoch Childrens Research Institute, Perpetual Philanthropy; the CASS Foundation; the Financial Markets Foundation for Children; and the National Health and Medical Research Council Australia. Dr Tang reports receiving research support from the National Health and Medical Research Council Australia; the Murdoch Children's Research Institute, Perpetual Trustees; the CASS Foundation; Financial Markets Foundation for Children; and the Food Allergy and Anaphylaxis Network. She is a member of the scientific advisory board on immunity and allergy and a member of the Medical Advisory Board Australia New Zealand for Danone Nutricia and a member of the Medical Advisory Board Oceania for Nestle Nutrition Institute; and has received speakers' fees from Danone Nutricia and travel support from the IUIS Primary Immune Deficiency Expert Committee and the World Allergy Organization. Dr Scurlock has disclosed no relevant financial relationships.

American Academy of Allergy, Asthma & Immunology (AAAAI) 2015: Abstract 508. February 22, 2015.


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