Sublingual Immunotherapy Safe, Effective For Peanut Allergy

Marcia Frellick

September 05, 2019

Peanut sublingual immunotherapy (SLIT) given in extended therapy up to 5 years provides significant desensitization for most peanut-allergic children, and is easy to use and safe, say the authors of a small study published online September 4 in the Journal of Allergy and Clinical Immunology.

SLIT involves placing a tiny amount of liquid peanut protein under the tongue, where it immediately enters the bloodstream, to desensitize allergic children to larger amounts of the protein. Sublingual application avoids digestion; therefore, dosing begins with very low amounts —  about 0.0002 mg initially — and the amount increases over months to just 2 mg. One peanut kernel contains about 300 mg of protein.

Edwin H. Kim, MD, assistant professor of medicine, Division of Rheumatology, Allergy and Immunology, at the University of North Carolina School of Medicine, Chapel Hill, and colleagues, found that 67% of the 48 patients in the open-label extension study who received 2 mg/day of peanut protein under the tongue for 5 years were able to tolerate at least 750 mg of peanut protein without serious side effects. About 25% of patients could tolerate 5000 mg.

Out of 75,366 total doses, 3599 (4.8%) doses were linked to symptoms affecting 45 participants. The most common side effect, representing 75% of reported symptoms, was itchiness around the mouth that lasted approximately 15 minutes and did not require treatment. It affected 3.6% of all doses taken.

"We now have the first long-term data showing that sublingual immunotherapy is safe and tolerable while offering a strong amount of protection," Kim said in a news release.

Currently, there are no US Food and Drug Administration (FDA)-approved treatments for peanut allergy. In addition to SLIT, treatments include oral immunotherapy (OIT), which is currently under FDA review (a decision is expected this year), and a skin patch that releases small amounts of peanut protein subcutaneously.

"We do need better treatment options than what we've seen so far," Corinne Keet, MD, PhD, associate professor of pediatrics at Johns Hopkins University School of Medicine in Baltimore, Maryland, told Medscape Medical News. "Even if oral immunotherapy is approved, there will still be safety concerns and the patch has problems with efficacy, so I think we will still be left with less-than-ideal solutions for food allergy treatments."

The authors of a recent meta-analysis published in the Lancet concluded that "available peanut oral immunotherapy regimens considerably increase allergic and anaphylactic reactions over avoidance or placebo, despite effectively inducing desensitization. Safer peanut allergy treatment approaches and rigorous randomized controlled trials that evaluate patient-important outcomes are needed."

In the current study, SLIT was found to provide comparable efficacy to OIT in peanut-allergic children. A recent phase 3, multinational study of peanut OIT demonstrated response rates of 76.6% to 443 mg of peanut protein, 67.2% to 1043 mg, and 50.3% to 2043 mg.

A recent multinational phase 3 study of the patch demonstrated a median cumulative reactive dose of 444 mg.

Keet said sublingual immunotherapy has been rising in the immunotherapy field as goals have shifted toward desensitization instead of allowing a large amount of consumption.

"When we compare those kinds of outcomes, this study of sublingual therapy over a long course of time actually looks favorable compared to other kinds of immunotherapy and the safety they reported was very high," she said.

She noted there was no need for epinephrine over the 5 years, "which is considerably less than we've been seeing for oral immunotherapy."

She did point out that there were some respiratory symptoms — a significant reaction — for 0.1% of the doses.

As for tolerability, the authors note that in the SLIT study, 23% of participants withdrew, with only two of the 11 individuals citing adverse events. For comparison, 25 of 238 (11%) active participants given the patch in a recent phase 3 study withdrew (four cited adverse events) and 80 of 374 (21%) OIT recipients withdrew from a phase 3 study (43 cited adverse events).

Keet cautioned that the study was small and had no control group, so there is no way to tell whether patients would have grown out of the peanut allergy without intervention. However, she noted, "generally we think that's less than 20%."

This study shows that sublingual immunotherapy is a valid approach, Keet said, but added, "I don't think we're anywhere near the end of the story in terms of treatments for food allergy."

Kim has reported consultancy with Aimmune Therapeutics, DBV Technologies, AllerGenis, and Allako, and clinical medical advisory board membership with DBV Technologies. Grant funding was received from the National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health, Food Allergy Research & Education (FARE), and the Wallace Research Foundation.

Coauthors have reported holding stock in Allertein, Mastcell Pharmaceuticals; being advisory board members for Aimmune Therapeutics, Consortia TX, and Prota Therapeutics; consulting for DBV Technologies and N-fold; receiving royalties from UpToDate; receiving speaking fees from Gordon Research Conferences and the Pediatric Allergy and Asthma Meeting; and conducting sponsored research with FARE and the National Institutes of Health. Keet has reported no relevant financial relationships.

J Allergy Clin Immunol. Published online September 4, 2019. Abstract

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