Dupilumab does not desensitize children with peanut allergy
Key takeaways:
- Researchers gave a double-blind placebo-controlled food challenge with at least 444 mg peanut protein to a pediatric population after receiving dupilumab for 24 weeks.
- Most children/adolescents did not pass.
Following receipt of dupilumab for 24 weeks, desensitization to peanut exposure in most children/adolescents with peanut allergy was not achieved, according to results published in Allergy.
“The impact of the findings for the everyday clinician is that dupilumab monotherapy may not be an effective treatment for desensitization in patients with peanut allergy,” Sayantani B. Sindher, MD, clinical associate professor of medicine and pediatrics – allergy and clinical immunology at Sean N. Parker Center for Allergy and Asthma Research at Stanford University, told Healio. “However, the reduction in total IgE and [peanut-specific]-IgE levels, as well as the decrease in allergic reactions of grade 2 or higher, suggest that dupilumab may still have a role in managing symptoms and reducing the severity of allergic reactions.
“Clinicians may need to consider combination therapies, such as allergen-specific immunotherapy, or alternative approaches to remove all sources of IgE to promote desensitization,” Sindher continued. “This is also valuable information for patients receiving dupilumab for other indications such as atopic dermatitis or eosinophilic esophagitis with concurrent food allergy and how to interpret results of food allergy testing.”
In a multicenter, single-arm, open-label, proof-of-concept phase 2 study, Sindher and colleagues assessed 24 children/adolescents (mean age, 11.7 years; 75% boys; 79.2% white; 95.8% with no history of allergen immunotherapy) with peanut allergy in the U.S. and Canada to determine the impact of subcutaneous dupilumab (Dupixent; Sanofi, Regeneron) given every 2 weeks on desensitization to peanut exposure by the 24-week mark.
Dupilumab dosing differed based on weight, with those weighing at least 60 kg (n = 4) receiving a 300 mg dose plus a 600 mg loading dose, and those weighing at least 20 kg but less than 60 kg (n = 20) receiving a 200 mg dose plus a 400 mg loading dose.
Researchers gave a double-blind placebo-controlled food challenge (DBPCFC) with at least 444 mg of peanut protein to each child/adolescent at the end of the study period and reported that only two children/adolescents (8.3%) passed the challenge. More common outcomes seen during this challenge included the use of adrenaline as rescue medication (n = 10; 41.7%) and grade 2 allergic reactions (n = 8; 33.3%).
Despite this outcome, 189.3 mg peanut protein was the mean dose for when adrenaline was required in this DBPCFC, demonstrating a rise from the baseline dose of 43.3 mg, according to the study. Further, more individuals had a grade 2 or grade 3 allergic reaction at the screening DBPCFC (n = 10).
Additionally, between baseline and week 24, researchers observed a 54% median decrease in total IgE. Peanut-specific-IgE also went down by a median of 49.3%, whereas peanut-specific-IgG4 did not change.
“Additionally, the decrease in basophil sensitivity and the reduction in [peanut-specific]-Th2A cells were not sufficient to prevent degranulation or modulate the immune response to peanut,” Sindher told Healio.
Another DBPCFC was conducted at the 36-week mark, in which only one of the two children/adolescents from above passed a DBPCFC with at least 1,044 mg of peanut protein.
In terms of safety, 66 mild to moderate treatment-emergent adverse events occurred in 15 children/adolescents.
“Over the 24-week treatment period, dupilumab was well tolerated and results were consistent with the known dupilumab safety profile,” Sindher and colleagues wrote.
According to the study, three treatment-emergent adverse events emerged as the most frequently reported, with each experienced by three individuals: injection site pain, injection site urticaria and headache.
“The study's findings contribute to our understanding of the potential role of dupilumab in managing peanut allergy and highlight the need for further research to optimize treatment strategies,” Sindher told Healio.
Researchers noted several limitations with regard to the study population, design, size and “lack of a comparator group.”
“Ongoing and future studies on dupilumab will investigate the potential of combining dupilumab with other therapeutics,” Sindher told Healio.
The ongoing Clinical Study Using Biologics to Improve Multi OIT Outcomes or COMBINE (NCT03679676) is investigating the potential of using both omalizumab and dupilumab as adjunct therapy with oral immunotherapy, she said.
“Future studies will likely continue to investigate combination therapies to promote desensitization with a focus on the long-term effects of dupilumab treatment,” Sindher continued.
For more information:
Sayantani B. Sindher, MD, can be reached at tina.sindher@stanford.edu.
Perspective
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Thinking about our approach to food allergy over the last 20 years, we have advanced from only recommending strict avoidance of the food allergen for all patients to, currently, having different treatment options. As multiple options for the treatment of atopic disease have become available, the use of a single medication for the treatment of multiple conditions is appealing.
The findings were surprising, as the hope was that dupilumab could be used for the treatment of food allergy, particularly because it has shown efficacy in the treatment of multiple atopic conditions including asthma, eczema, chronic rhinosinusitis with nasal polyps, prurigo nodularis and eosinophilic esophagitis.
In my experience, I have seen patients with eosinophilic esophagitis with concomitant food allergy who have had accidental ingestion of their food allergen and have had allergic reactions after, including anaphylaxis. On the other hand, I have seen young patients with improvement in their food allergy, while on treatment with dupilumab for eczema, even in food allergies that are not usually “outgrown” at an early age.
I believe that further studies are needed to better understand which patients with food allergy could benefit from treatment with dupilumab. It would also be important to study patients over a longer treatment period, as this could make a difference in response, as decreased levels of both total and peanut-specific IgE were noted over time, although desensitization to peanut was not seen with dupilumab monotherapy. The study also included a small number of patients, primarily white boys, so a study with larger numbers of patients and a diverse patient population, more consistent with the actual number of patients with peanut allergy, would be interesting. I am looking forward to larger studies of dupilumab in patients with different food allergies, from diverse backgrounds, and at different ages.
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