Report from AAAAI/WAO 2018: A Spotlight on FARE-Supported Research
Last weekend, representatives from FARE attended a joint congress of the American Academy of Allergy, Asthma & Immunology (AAAAI) and the World Allergy Organization (WAO) in Orlando, FL. As we wrap up our reporting from AAAAI/WAO 2018, we summarize findings from wide-ranging studies that received support from FARE, including investigations of oral food challenges with mixed tree nuts, peanut allergy biomarkers, sublingual immunotherapy to treat peanut allergy, and patient-centered food allergy research. Lastly, we conclude with late-breaking reports from Aimmune’s PALISADE trial for its peanut oral immunotherapy product, AR101, and DBV’s PEPITES trial for its epicutaneous peanut immunotherapy product, Viaskin Peanut.
Individuals with allergy to one tree nut often have allergies to other tree nuts. As a result, many patients avoid tree nuts to which they may not be allergic. Moreover, evaluation of tree nut allergies can involve multiple oral food challenges (OFCs) for separate tree nuts, each of which carries the risk of a severe reaction. To minimize the burden of tree nut allergy diagnosis and management, researchers are testing the safety and utility of mixed tree nut OFCs at Arkansas Children’s Hospital, a member site within the FARE Clinical Network of leading food allergy centers.
Among patients who were actively restricting tree nuts from their diet, 44 nut-allergic participants aged 3 to 21 were identified through clinical histories, tree nut-specific IgE and skin prick tests. Additional allergic conditions, namely hay fever, eczema, and other food allergies, affected more than half of the participants. Mixed tree nut OFCs, in which 10 grams of each nut was administered in incremental doses, involved combinations of three of the following tree nuts: walnut, pecan, almond, cashew, hazelnut, pistachio, Brazil nut and pine nut.
More than three-quarters of the patients (34 out of 44) passed the mixed tree nut OFC. Phone surveys six months later found that 30 of the 34 had added all tree nuts into their diet while the remaining 4 added only the nuts from their challenge. Of the 10 who failed the mixed nut OFC, most reported mild to moderate symptoms at the time, and none required epinephrine. Almond, pecan, cashew and walnut were the most commonly tested tree nuts. Long-term follow-up phone surveys are ongoing, but 73 percent of those surveyed to date continue to eat and tolerate tree nuts.
Dr. Erik Wambre, who in 2015 received a FARE Investigator in Food Allergy Award, last year identified a class of immune cells, called Th2A cells, found only in individuals with allergies. Working with fellow scientists at Benaroya Research Institute at Virginia Mason, Wambre and colleagues investigated interleukin-33 (IL-33), a protein produced and released by some immune cells. Recent research shows that IL-33 can make allergic immune responses stronger.
Analyzing cells in blood samples from individuals with peanut allergy, the researchers determined that, upon activation, the allergy-associated, peanut-specific Th2A cells produced the cell-surface receptor for IL-33, while other peanut-specific T cells did not. The Th2A cells were more prevalent in children than adults.
By making the IL-33 receptor, a protein called ST2, the allergy-associated cells Th2A become able to respond to IL-33. Because IL-33 can influence the activity of cells found only in people with allergies, IL-33 may be a good target for drugs to treat allergic diseases.
Previous research has compared two treatments for peanut allergy: oral immunotherapy (OIT), in which increasing doses of peanut protein are eaten, and sublingual immunotherapy (SLIT), in which smaller doses of peanut protein are dissolved in a solution that is held under the tongue for a time before being spat out or swallowed. These past studies have found that both approaches can desensitize most patients to a degree that is likely to prevent allergic reactions after accidental ingestion. SLIT appears to provide less robust desensitization than OIT, but is better tolerated.
A recent peanut OIT study found that, compared to historical results in older children, preschoolers achieved higher rates of sustained unresponsiveness, that is, the ability to discontinue OIT and still pass an oral food challenge (OFC) at a later date, typically some weeks later. Peanut SLIT has not been tested in this younger age group.
To investigate peanut SLIT in preschoolers, researchers at the University of North Carolina, Chapel Hill, have established a cohort of 40 children aged 12-48 months with peanut allergy. The investigators presented screening data and results for entry OFCs. Subsequent FARE-funded research will test the safety and efficacy of peanut SLIT in these very young children.
FARE’s Outcomes Research Advisory Board (ORAB) was created in 2016 to give food allergy patients a voice in setting the research agenda. In addition to food allergy patients and parents, ORAB participants include academic scientists, clinicians, other healthcare providers, educators, and representatives from industry.
The ORAB collaborated in the creation of a survey tool for assessing food allergy research priorities. The survey was completed by a national sample of 45 food allergy researchers and 62 non-researchers prior to the 2017 FARE Research Retreat. Non-researchers included parents of food-allergic children (65 percent), individuals with food allergies (11 percent) and members of advocacy organizations (21 percent). No previous studies have compared the food allergy research priorities of researchers and patient advocates.
Both groups were most likely to prioritize new medical interventions. More researchers (46 percent) than non-researchers (30 percent) selected the development of a desensitization treatment as their top-ranking priority, while roughly equal percentages of researchers and non-researchers prioritized the development of a cure over other choices (30 percent vs. 28 percent).
Non-researchers were twice as likely as researchers to give highest priority to product labeling research (14 percent vs. 7 percent) and five times as likely to select psychosocial research as the highest priority (10 percent vs. 2 percent). There were no significant differences in research priorities based on gender, educational level, having observed anaphylaxis, or having a first-degree relative with food allergies.
These findings fleshed out additional details from the PALISADE trial, for which topline results were reported last month. The patients aged 4-17 who participated in the trial were highly allergic, with 43 percent having peanut-specific IgE (psIgE) levels exceeding 100 kU/L. The median dose patients tolerated on entry to the trial was 10 mg, or about one-thirtieth of a peanut. More than half had been diagnosed with asthma, nearly two-thirds had multiple food allergies, and almost three-quarters had a history of anaphylaxis.
About 1 in 5 patients who received active treatment (the characterized peanut product AR101) left the study early, as did 1 in 15 patients who received placebo. At the end of the trial, half of the AR101-treated participants who started the trial tolerated each dose in the exit food challenge to an endpoint of 1,000 mg, as did 63 percent of active-treatment participants who completed the trial. By comparison, less than 3 percent of placebo-treated patients could tolerate all doses up to the endpoint
Patients with baseline psIgE levels at or below 100 kU/L tended to have better outcomes, with a higher rate of completion, fewer withdrawals due to gastrointestinal symptoms, better response to the 1000-mg endpoint, and no severe treatment-related adverse events. The overall incidence of serious adverse events among participants taking AR101 was about 1 percent, including one instance of anaphylaxis. Most AR101 patients (86 percent) experience no adverse effects.
FARE Blog also reported on findings from the PEPITES trial last month. In evaluating the efficacy and safety of Viaskin Peanut 250 µg in children ages 4 to 11, PEPITES did not meet its primary endpoint for efficacy, which was based on differences in the response rates to treatment and placebo. However, differences in response rate and cumulative reactive dose (CRD, the total amount consumed in an oral food challenge before a reaction occurred) between treatment and placebo were statistically significant. The safety profile of peanut epicutaneous immunotherapy was favorable. Allergy-associated peanut-specific IgE antibodies declined and IgG antibodies associated with peanut tolerance increased in the treated population.