New Guidelines, Potential Therapy Offer a Shift in the Prevailing Wind
Peanuts are considered one of nature's healthiest foods ... unless, of course, you are one of the three million Americans allergic to peanuts and tree nuts. For those with severe allergy, even minimal exposure to peanut protein could prove deadly.
While it might seem counterintuitive to parents fearful of harming their children, the potential severity of an allergic reaction is one of the reasons ... backed by science ... that clinical guidelines were changed in January to call for a much earlier introduction of peanuts in the diet. For years, healthcare providers have told new parents not to introduce peanut products until the age of two. Yet, the incidence rate of peanut allergies has continued to climb in the United States.
In January, the National Institute of Allergy and Infectious Disease (NIAID), along with the American Academy of Allergy, Asthma & Immunology (AAAAI) plus 24 other organizations, recommended children at high risk of peanut allergy be introduced to peanuts at four to six months instead of avoiding all peanut-containing foods.
The about-face was prompted by findings from the NIAID-funded Learning Early About Peanut (LEAP) allergy trial, which showed children at high risk of developing a peanut allergy were far less likely to do so (an 81 percent relative reduction) when introduced to peanuts before turning a year old. After the LEAP results came out, the NIAID convened a panel of experts for a review of literature and other studies that culminated in the addendum updating the 2010 Guidelines for the Diagnosis and Management of Food Allergy in the United States. The new addendum, which was published in the Jan. 5 edition of the AAAAI's Journal of Allergy and Clinical Immunology, has detailed information on when and how to introduce peanuts to infants at three different risk levels. The new guidelines also call for adults to consult a healthcare provider before introducing peanuts to a child's diet.
Infants at highest risk of peanut allergy - those with severe eczema, egg allergy or both - should be brought to a specialist for peanut sIgE or skin prick testing to assess signs of allergy and to decide the safest way to introduce the peanut, which could include supervised feeding under the watchful eye of a healthcare provider. In the LEAP study, only 1.9 percent of infants at high risk of allergy who were introduced to peanuts early went on to develop a peanut allergy by age five, as compared to 13.7 percent of children in the same risk group who avoided peanuts.
To access the addendum guidelines, go online to the 'Diseases and Conditions' section of NIAID.NIH.gov.
For those who have already developed a peanut allergy, a new form of epicutaneous immunotherapy has continued to show promise in clinical trials. The Viaskin® Peanut patch has progressed from a Phase Ib safety trial launched in July 2010 to two Phase III trials now underway focused on safety, long-term efficacy and real world use.
Viaskin Peanut patch (Photo: Courtesy DBV Technologies)
Luis Salmun, MD, senior vice president of Global Medical Affairs for clinical-stage biopharma company DBV Technologies, said the company's novel patch mechanism is very exciting and could be used with other allergens and diseases, as well. In addition to the peanut patch, DBV Technologies is exploring the platform to address milk and egg allergies and is in a Phase I trial for pertussis.
"This is a new platform for technology that uses the skin as an immune organ ... not just a barrier but actually as an immune organ," said Salmun.
The Viaskin technology differs from other patches presently on the market, such as those to wean individuals from smoking, "The kind of patches that are used currently are absorbed quickly through the skin," Salmun explained. "With the Viaskin patch, what's different is that there is a space between the patch and the skin. This membrane is electrostatically charged with peanut protein. The space allows for the very slow release of the peanut protein from the patch to the skin."
He continued, "Once deposited on the skin, it (peanut protein) binds to Langerhans cells, the antigen-presenting cells, and goes directly to the lymph nodes, bypassing the bloodstream." Salmun pointed out this route, which was studied in animal models, minimizes the chance of systemic reaction and anaphylaxis. "That is one of the key advantages of this technology."
Thus far found to be most efficacious in the pediatric population, Salmun said the dose released in children aged four-11 is 250 micrograms - approximately 1/1000th of a peanut in each patch. "What is so exciting is that such a negligible amount of peanut protein can lead to such an immune response," noted Salmun.
At the recent AAAAI annual meeting, a team from DBV presented findings from a two-year extension of their successful yearlong, double blind, placebo-controlled, randomized trail for Viaskin Peanut. In the two-year extension arm, participants were treated with a daily 250 µg peanut patch. At the end of the third year, 83.3 percent of children aged six-11 showed response to treatment, as compared to 53.6 percent at the end of the one-year trial. In this trial, a responder after three years of treatment was defined as a patient who reached an eliciting dose equal to or greater than 1,000 milligrams of peanut protein, or had a greater than 10-fold increase of the eliciting dose compared to the patient's baseline eliciting dose at the beginning of the Phase II trial.
Similarly, children using the Viaskin Peanut patch saw a marked increase in the amount of peanut they could ingest during food challenges. At study entry, the median cumulative reactive dose was 44 milligrams of peanut protein. For those who completed three years in the extended trial, the median cumulative reactive dose rose to 1,440 milligrams.
Salmun pointed out, "The goal of Viaskin is to decrease the chances of a reaction to an accidental exposure ... not to eat PBJ sandwiches." However, he continued, it's an important goal given the number of Americans with peanut allergies and the difficulty in predicting the severity of reaction on any given day, which might range from a skin reaction to severe anaphylaxis. "The incidence of peanut allergy has increased significantly over the past decade," he added.
While the latest studies have shown increased tolerance by extending use of the patch from one year to three, Salmun said there isn't an exact answer at this point as to the optimal timeframe for wearing the disposable patch. "How to stop ... when to stop ... we don't have an exact answer at this time," he noted. In fact, Salmun continued, "I don't think there's going to be a black or white answer ... it will have to be evaluated by the physician."
Results from the latest Phase III studies are expected in the second half of 2017. What is already known is that patients have been able to tolerate the patch very well with no serious adverse events being reported. The trials have also enjoyed well over 95 percent compliance rate for the small, easily applied patch. Salmun said there are no constraints or restrictions with the patch and that children in the trials have been able to swim, run and play sports as normal.
In a Nutshell
Quick facts and stats about food allergies according to FARE (Food Allergy Research & Education):