Sublingual Immunotherapy Safe Alternative for Peanut Allergy

Kate Johnson

February 25, 2015

HOUSTON — Sublingual immunotherapy continued for up to 5 years can induce "sustained unresponsiveness" in some peanut-allergic children, according to an extended trial.

"I do not use the word 'tolerance' because there's not really a good definition in our field right now of what tolerance truly means after stopping therapy," said senior investigator Wesley Burks, MD, from the University of North Carolina at Chapel Hill.

The findings are encouraging, but they pale in comparison to the much better results seen with oral immunotherapy, Dr Burks told Medscape Medical News. However, "sublingual immunotherapy is much safer than oral immunotherapy, so there may be a role for a combination of the different types of therapy."

When the original analysis was presented at the 2013 meeting of the Academy of Allergy, Asthma & Immunology (AAAAI), five of the first 11 patients to complete 3 years of therapy passed a double-blind placebo-controlled food challenge with 5 g of peanut protein 1 month after stopping sublingual immunotherapy, as reported by Medscape Medical News.

"The study was extended to 5 years to see if longer treatment with peanut sublingual immunotherapy would improve the effect," explained lead investigator Edwin Kim, MD, also from the University of North Carolina at Chapel Hill. Dr Burks presented data from the extended study here at AAAAI 2015.

The 47 peanut-allergic children enrolled in the extended study were 1 to 11 years of age (mean, 6.3 years). They were randomized to receive daily sublingual peanut protein 2 mg or placebo.

To date, 11 patients have completed 3 years of therapy and 14 have completed 5 years of therapy.

Of these 25 patients, 17 did not pass a 5 g food challenge without symptoms. However, five patients passed a challenge after 3 years of therapy and three passed after 5 years of therapy.

The findings are encouraging, but they pale in comparison to the much better results seen with oral immunotherapy.

These children "were able to safely eat 16 peanuts, even after stopping the drops for 1 month, showing a lasting benefit that we call sustained unresponsiveness," Dr Kim told Medscape Medical News.

Despite the fact only eight patients achieved sustained unresponsiveness, some of the others reached a point where they could tolerate 1400 mg of peanut protein, which is "an adequate amount," said Dr Burks. That means they could tolerate 4 or 5 peanuts before symptoms developed.

Overall, the big advantage of sublingual immunotherapy is that it is extremely safe. In fact, "other than oropharyngeal itching, which you would expect, allergic side effects were relatively uncommon, and no one was treated with epinephrine," Dr Burks reported.

Mechanistic studies showed "all the parameters that we correlate with successful immunotherapy," he said.

Decrease in Immunoglobulin Levels

After therapy, there was a decrease in mean peanut-specific immunoglobulin (Ig)E levels (from 120.39 to 43.61 kU/L; P < .001) and median wheal size (P = .0069). In addition, there was an increase in mean peanut-specific IgG4 (from 0.41 to 37.52 mg/L; P < .001).

"It's not clear if the increased threshold in partially desensitized subjects lasts after stopping the drops because only those who were fully desensitized were tested," Dr Kim explained. "This could be important if the goal becomes to protect against small accidental ingestions, as opposed to the current goal of having kids tolerate a large amount of peanut."

Although it is estimated that 20% of children outgrow peanut allergy, this is thought to happen before the age of 5 years. In children older than 5, "the chances are very small," he said. "Kids in this study were median of 6.4 years at entry and 10.4 years at study completion."

This study highlights the differences in the robustness of effect between oral immunotherapy and sublingual immunotherapy, said session moderator Amy Scurlock, MD, from Arkansas Children's Hospital in Little Rock.

"But it shows you can still get some clinical effect with sublingual immunotherapy. It may just depend on the dose and duration and other modifiable factors we need to evaluate," she added.

Although results are less dramatic with sublingual immunotherapy than with oral immunotherapy, sublingual immunotherapy still has a place in allergy therapy, said Dr Scurlock.

"Down the road, as we think about more personalized approaches to treating food allergy, we might have an approach where we initially do sublingual immunotherapy — for example, in a very sensitive patient — and then convert to oral immunotherapy. Or we might do some other combination or sequence of therapy. Those trials haven't been done yet, but that might be the future," she said.

Dr Burks reports that he chairs the research advisory board for Food Allergy Research & Education; receives grants from Hycor and Allergen Research Corporation; consults for Dow AgroSciences, GLG Research, Hycor Biomedical, Merck, ExploraMed Development, Perrigo Company, Regeneron Pharmaceuticals, Genalyte, Dynavax Technologies, Perosphere, ActoGeniX, SRA International, Genentech, and Sanofi US Services; is a speaker for Mylan Specialty; and holds stock in Allertein. Dr Kim and Dr Scurlock have disclosed no relevant financial relationships.

American Academy of Allergy, Asthma & Immunology (AAAAI) 2015: Abstract 507. February 22, 2015.


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