A New Way to Treat Peanut Allergy
Our immune system must constantly maintain a delicate balance, reacting to foreign pathogens while tolerating non-harmful substances such as foods. Allergy is a dysregulation of this balance that causes an inflammatory reaction to benign proteins. One of the most dangerous is allergy to peanuts, the prevalence of which appears to have increased 21 percent since 2010 and has been associated with more life-threatening reactions. Patients and parents are currently left with strict avoidance as their only option, in a world where peanuts lurk in countless places.
In an allergic reaction, an allergen causes a response in a type of immune cell called T helper type 2 (Th2), which results in generation of IgE antibodies and inflammatory signaling proteins that lead to the characteristic symptoms of allergy, including runny nose, hives, swelling, vomiting, throat tightness or wheezing. Therapeutic approaches seek to desensitize the immune system and correct this immune response. Desensitization relies on activation of regulatory T cells (Tregs) that act as suppressors, helping to reduce Th2 responses and producing anti-inflammatory proteins.
Exposure therapy that treats peanut allergy through supervised ingestion of tiny amounts of peanut protein over time has been shown to provide some benefit, supported by data published in November 2018 in the New England Journal of Medicine. This peanut oral immunotherapy is currently being reviewed by the FDA. However, desensitization through oral routes allows the allergen protein to enter into the bloodstream, increasing the risk of systemic allergic reactions. This is why scientists are exploring new and safer ways to desensitize the immune system through alternate routes.
A novel solution is currently being studied in clinical trials. Researchers at DBV Technologies have developed an immunotherapy for food allergy delivered via a skin patch. This epicutaneous immunotherapy (EPIT) exposes the skin to a tiny amount of peanut protein (250 micrograms, or about 1/1000th of a peanut, as a daily epicutaneous dose, compared to 300 milligrams, or about one peanut, as the oral immunotherapy maintenance daily dose), harnessing the power of immune cells in the epidermis to minimize the chance of systemic absorption.
In EPIT, peanut protein delivered through the patch is captured by Langerhans cells in the epidermis. Langerhans cells are specialized antigen-presenting cells (also known as dendritic cells) of the skin, which process the peanut protein, migrate to lymph nodes and present the antigen to T cells. In the lymph nodes, this activates Tregs to ultimately suppress the allergic response.
Data from the Phase III trial of EPIT for peanut allergy in patients ages 4–11 years were recently published in JAMA. The study found that a significantly greater proportion of patients treated with EPIT (35.3 percent) demonstrated an increase in the amount of peanut protein required to elicit an allergic reaction during food challenge compared with the placebo group (13.6 percent). The trial did not meet a component of the primary end point, defined as the prespecified 15 percent lower bound of the confidence interval between treatment groups.
However, because this is the first study of its kind, it remains to be seen whether an effect size below this cutoff could still translate to clinical significance; in other words, the meaning of missing this statistical end point with respect to treating peanut-allergic patients remains to be determined. In addition, approximately two thirds of patients on active peanut EPIT had any increase in the amount of peanut protein tolerated after a year of treatment; as a result, patients on peanut EPIT were more than four times as likely to have an increase in this eliciting dose compared to placebo patients.
From safety and practicality perspectives, peanut EPIT was well-tolerated. Systemic allergic reactions rarely occurred, and none of these were severe. Adherence to using the treatment was very high at over 98 percent in the peanut EPIT group, which points to the convenience of using this type of therapy over other forms that may place more restrictions on daily activities when taking oral daily doses. Therefore, I believe the data thus far support the potential of EPIT’s efficacy, safety and practicality profiles.
Therapies that modulate the immune system have shown enormous potential across diverse disease areas, from atopic dermatitis to cancer. The challenge across all of these therapies is activating specific immune processes in a safe and controlled manner. The approach of targeting the immune system through the skin has important properties for clinical utility. Most importantly, a greater safety profile, as well as high ease of use, suggest that EPIT could potentially serve as a convenient and tolerable treatment option for peanut allergy.
I am excited about the recent advances I’ve seen in food allergy treatment—an area in which patients, including young children, still need a safe and effective treatment option. While the research is ongoing, these data and others represent a new path forward for treating this challenging disease.