Equivocal Results for Peanut Allergy Skin Patch

Troy Brown, RN
February 22, 2019

A skin patch that delivers immunotherapy for peanut allergy resulted in a significantly higher response rate than placebo, according to an article published online today in JAMA. However, the results failed to meet a primary trial endpoint, which makes interpretation difficult.

Currently there are no treatments for peanut allergy approved by the US Food and Drug Administration (FDA). Whereas some groups are testing oral or sublingual immunotherapy, the risk for serious adverse events, including anaphylaxis, is thought to be lower with epicutaneous immunotherapy delivered via a skin patch.

To test the skin patch, David M. Fleischer, MD, from Children's Hospital Colorado, University of Colorado Denver School of Medicine, Aurora, and colleagues conducted a phase 3, randomized, double-blind, placebo-controlled trial at 31 sites in five countries. The study included 356 children aged 4 to 11 years (median age, 7 years; 61.2% male) with peanut allergy but no history of a severe anaphylactic reaction who experienced objective symptoms when given an eliciting dose of 300 mg or less of peanut protein during a double-blind, placebo-controlled food challenge.

The investigators randomly assigned participants to receive daily treatment with a skin patch that contained either 250 µg of peanut protein (n = 238) or placebo (n = 118) for 12 months.

The study's primary outcome was the difference in response rate between the peanut protein and placebo groups after 12 months. The researchers defined treatment response as a posttreatment eliciting dose of 300 mg or more for the low-eliciting dose subgroup or 1000 mg or more of peanut protein for the high-eliciting dose subgroup.

The overall response rate was 35.3% among those who received the peanut patch treatment compared with 13.6% for those who received a placebo (difference, 21.7%; 95% confidence interval [CI], 12.4% - 29.8%; P < .001). However, the study did not meet the prespecified lower bound of the CI threshold at 15%.

"The clinical relevance of not meeting this lower bound of the confidence interval with respect to the treatment of peanut allergic children with epicutaneous immunotherapy remains to be determined," Fleischer and colleagues write.

The most common treatment-emergent adverse events (TEAEs) were patch application site reactions, which developed in 95.4% of patients in the active group and 89% of patients in the placebo group. Other TEAEs included pruritus (peanut patch, 34.5% vs placebo patch, 11.9%), erythema (28.2% vs 16.9%), and swelling at the application site (16% vs 1.7%).

Given the clinical need and lack of available treatments, the new data are important, Jody W. Zylke, MD, deputy editor, JAMA, writes in an accompanying editor's note. "However, the results are not easy to interpret."

The difference in response between the two groups was statistically significant "by traditional statistical measures. However, the definition of a clinically significant response, recommended by the Food and Drug Administration and agreed to by the sponsor, was that the lower bound of the 95% CI around the difference should meet or exceed 15%. The lower bound of the 95% CI was 12.4%, meaning the main result did not reach the criterion for a positive trial result," Zylke explains.

"The authors argue that the 15% cutoff was arbitrary, based on convention, and that no thresholds have been set to guide assessment of food allergy immunotherapy. Clinicians will have to determine with patients whether a response of 35.3% with the peanut patch is worthwhile," he continues.

"In addition, the effectiveness, adverse events, adherence, and durability of epicutaneous therapy must be weighed against the similar metrics with alternative types of therapy, such as oral immunotherapy," Zylke concludes.

Fleischer reports receiving institutional research funding from DBV Technologies and Aimmune Therapeutics; serving as a consultant and receiving personal fees from DBV Technologies, Aimmune Therapeutics, Kaleo Pharmaceutical, INSYS Therapeutics, Abbott, and Nestle; and being an unpaid member of the scientific advisory council for the National Peanut Board and an unpaid member of clinical advisory boards for Food Allergy Research and Education and Food Allergy and Anaphylaxis Connectivity Team. The remaining authors report a variety of financial relationships with multiple pharmaceutical and medical companies and medical organizations. A complete list is available on the journal's website. Zylke has disclosed no relevant financial relationships.

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SOURCE: Medscape, February 22, 2019. JAMA. Published online February 22, 2019.

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