Immunotherapy skin patch could address ‘urgent’ need among toddlers with peanut allergy
Click Here to Manage Email Alerts
Key takeaways:
- 67% of the children who used the skin patch and 33.5% of those on placebo met the trial’s primary end point.
- 0.4% of the treatment group experienced serious treatment-related adverse events.
Epicutaneous immunotherapy was superior to placebo in desensitizing toddlers to peanuts and in increasing the dose of peanuts that trigger allergic symptoms, according to a study published in The New England Journal of Medicine.
Efficacy findings were consistent across subgroup and sensitivity analyses, and safety profiles were acceptable as well, Matthew Greenhawt, MD, MBA, MSC, director of the food challenge and research unit at Children’s Hospital Colorado, and colleagues wrote.
“There exists an urgent unmet medical need for infants and toddlers living with peanut allergy. Peanut allergy affects approximately 2% of U.S. children and has been a growing public health problem over the past 20 years,” Greenhawt told Healio. “Growing evidence suggests that the allergic immune system is more modifiable early in life.”
Currently, children aged 4 years and younger with peanut allergy can be treated with oral immunotherapy, but this treatment involves arduous administration schedules and a risk for treatment-associated systemic adverse events, the researchers said.
“There are currently no FDA approved treatment options for toddlers under 4 years old,” Greenhawt said. “Evidence shows that most children are initially diagnosed with peanut allergy between the ages of 1 and 4 years old.”
As a physician, Greenhawt said, he has noted that the availability of multiple treatment options is important to both patients and caregivers.
“What works for one family may not work for another, with the best option being specific to what a family is seeking in terms of preference,” he said.
With research showing that many families prefer nonoral options for immunotherapy, Greenhawt said that Viaskin Peanut (DBV Technologies) may prove to be a viable choice for these individuals.
“Viaskin Peanut uses a novel approach called epicutaneous immunotherapy (EPIT), which is a route of desensitization that takes advantage of the skin being the largest immune organ in the body,” Greenhawt said. “Viaskin Peanut produces a level of protection utilizing much smaller doses of peanut protein compared to an oral therapy.”
EPIT is applied once a day, Greenhawt continued, and the dose is rarely associated with systemic side effects.
“Moreover, the child’s activities do not need to be adjusted around the dose, and it can even be applied when the child is ill, which is different than other therapies,” he said.
The EPITOPE trial
The phase 3, multicenter, double-blind, randomized, placebo-controlled Epicutaneous Immunotherapy in Toddlers with Peanut Allergy (EPITOPE) trial enrolled 362 patients (median age, 2.5 years; 68% boys; 63.3% white) aged 1 to 3 years between July 31, 2017, and April 27, 2022, at 51 sites in eight countries.
“The findings from the EPITOPE trial are meaningful, as they show the potential clinical benefit of the Viaskin 250 µg peanut patch,” Greenhawt said.
There were 244 patients in the intervention group and 118 in the placebo group. The Viaskin Peanut patch with 250 µg of peanut protein, equal to one-thousandth of a peanut, or a placebo patch was applied to the patient’s interscapular area each day for 12 months.
Also, 67 patients had an eliciting-dose level of 10 mg or less, and 295 had an eliciting-dose level greater than 10 mg. Overall median patch exposure was 376 days (interquartile range [IQR], 368-419).
The intervention group had a median average daily duration of 22.2 hours (IQR, 19.4-23.4) and the placebo group had a median average daily duration of 23.7 hours (IQR, 22.9-24). Mean adherence overall was 97% ± 6.9%, with 84.8% of patients completing the assigned intervention or placebo use.
At 12 months, 67% of the intervention group and 33.5% of the treatment group (percentage point difference, 33.4; 95% CI, 22.4-44.5) went from a baseline eliciting dose of more than 10 mg to a post-treatment eliciting dose of at least 1,000 mg (approximately three to four peanuts, or between four and five peanut M&Ms) or went from a baseline eliciting dose of 10 mg or less to at least 300 mg post-treatment, which the researchers called responder end points.
Median changes in cumulative reactive doses from baseline to month 12 included 1,300 mg (IQR, 140-3,000) for the intervention group and 0 mg (IQR, 0-1,000) for the placebo group. Median changes in eliciting doses from baseline to month 12 included 900 (IQR, 90-1,700) for the intervention group and 0 mg (IQR, 0-700) for the placebo group.
Regardless of their baseline eliciting dose subgroup, 64.2% of the intervention group and 29.6% of the placebo group had an eliciting dose of at least 1,000 at 12 months (percentage point difference, 34.7; 95% CI, 23.6-45.7). Also, 37% of the intervention group and 10% of the placebo group had a cumulative reactive dose of at least 3,444 mg at 12 months (percentage point difference, 27; 95% CI, 17.9-36.1).
Adverse events
Proportions of mild, moderate and severe objective signs and symptoms were balanced in the intervention and placebo groups at baseline, but the distribution of maximum symptom severity shifted to less severe symptoms in the intervention group at month 12, coincident with increased eliciting doses and more patients meeting responder end points.
Peanut-specific IgE levels decreased for the intervention group but increased for the placebo group from baseline to month 12. Also, peanut-specific IgG4 levels increased for the intervention group but saw little change for the placebo group from baseline to month 12, the researchers said.
Every patient in the intervention group and 99.2% of the placebo group experienced adverse events, most commonly application-site reactions such as erythema (98% and 90.7%), pruritis (94.7% and 61%) and site swelling (72.5% and 39%).
Skin reactions, which mostly included erythema, erythema and infiltration, and erythema and few papules happened more often during the first 3 months and then gradually decreased through the study period for the intervention and placebo groups alike.
Also, 81.6% of the intervention group and 55.1% of the placebo group had local adverse events during the treatment period that lasted more than 90 days, with 95.9% of the intervention group and 63.6% of the placebo group using a topical corticosteroid for these reactions at least once.
There were 21 patients in the intervention group (8.6%) and three in the placebo group (2.5%) who experienced serious adverse events, excluding those that took place during food challenges, as well.
Similarly, 7.8% of the intervention group and 3.4% of the placebo group reported anaphylaxis, including 26 reactions outside food challenges in 17 patients in the intervention (7%) group and three patients in the placebo group (2.5%) that were systemic adverse events of special interest.
The researchers considered four anaphylactic reactions (1.6%), all among the intervention group and all with mild or moderate severity, to be related to treatment.
Eight patients in the intervention group (3.3%) discontinued participation in the study after experiencing 14 events, and the researchers said that the events that led seven of these patients to leave possibly were related to the intervention.
Conclusions
Noting the superiority of treatment compared with placebo, the researchers said that EPIT for peanut allergy may reduce the likelihood of allergic reactions upon accidental exposure as an alternative to OIT for children in this age group.
“While this therapy is still under investigation and not approved by the FDA, it could one day fulfill a huge unmet medical need for children and their families,” Greenhawt said.
“The study data show that Viaskin Peanut is a minimally invasive, nonoral treatment that presents minimal disruption to the child’s daily life, while still safely providing a high level of protection,” he continued.
Next, Greenhawt said, the FDA has requested additional safety data to get closer to 600 patients in the study’s safety database, which would be consistent with the administration’s approach to Viaskin Peanut for children aged 4 to 7 years.
For more information:
Matthew Greenhawt, MD, MBA, MSC, can be reached at matthew.greenhawt@childrenscolorado.org.
Perspective
Back to Top
Aikaterini (Katherine) Anagnostou, MD (Hons), MSc, PhD
The recent results reported from the EPITOPE trial by Greenhawt et al. are very encouraging for young patients with peanut allergy and their families. The multi-center, international research trial showed that 67% of toddlers aged 1 to 3 years receiving patch immunotherapy, compared with 33.5% receiving placebo, were able to ingest approximately one to four peanuts after 1 year of treatment. The rate of treatment-related anaphylaxis was low (1.6%). Severity of allergic reactions observed during oral food challenges decreased post-therapy. The overall protective effect of EPIT is likely lower compared with OIT, but epinephrine use appears to be lower with EPIT.
Future consultations with patients and families of food-allergic children will likely focus on shared decision-making to arrive at the best choice for each family based on individual values and preferences. The future of food allergy certainly looks promising with many different treatments on the horizon (currently under development) and, hopefully, many more available options for therapy for food-allergic individuals. Future research should focus on other common food allergens as well, such as milk and egg, in addition to peanut.
Perspective
Back to Top
It is an exciting and hopeful time in food allergy where there are multiple treatments on the horizon. The findings of the EPITOPE study are very significant. As the authors mention, there is not currently any FDA-approved treatment option for children aged younger than 4 years. This study showed that the peanut patch appears to be relatively safe and effective in some children aged 1 to 3 years.
There are pros and cons to each type of food allergen immunotherapy. EPIT appears to be safer than OIT, with the most common adverse reaction being application-site reactions and rare GI symptoms. Another potential benefit to EPIT is that in many ways, it is practically easier and may be more tolerable to some. There are not the same limitations around dosing, such as waiting to exercise, buildup can be done at home by wearing the patch for longer without the need for frequent doctor’s office visits, and nothing is ingested so taste aversion does not play a role.
However, prior studies indicate that OIT can lead to a higher desensitization threshold compared with EPIT. This is important when discussing goals of treatment with each family. Furthermore, EPIT seems to be most effective in younger children, as there was a higher responder rate among children aged 1 to 3 years than seen in the PEPITES trial, which involved children aged 4 to 11 years. Many of these factors could impact the real-world uptake of this product from both the parent and allergy provider’s perspective.
While these results are exciting, it is important to recognize that while a larger percentage of patients in the peanut patch group met the responder end point compared with the placebo group, not all children on treatment met the primary endpoint (67%). Future studies should try to identify patients who are most likely to benefit so that this can be used to develop shared decision-making tools. In addition, an important next step will be more long-term data on safety, efficacy, adherence and impact on quality of life.
Reference:
Fleischer DM, et al. JAMA. 2019;doi:10.1001/jama.2019.1113.
Collapse
Read more about
Click Here to Manage Email Alerts