New research from NCRC affiliated researchers Prof. Jonathan Hourihane and Dr Aideen Byrne has shown that treatment with a peanut-derived oral immunotherapy (AR101) leads to rapid desensitisation to peanut in children and adolescents with a diagnosis of peanut allergy.
Peanut is the most common cause of both food allergy related anaphylaxis and emergency department admissions among children and adolescents. Peanut allergy is difficult to manage as peanut is a common ingredient in foodstuffs and allergic responses can be triggered by even small amounts.
The current standard of care for peanut allergy is strict dietary restriction and the use of emergency medications (e.g. auto-injectable adrenaline) following accidental exposure to peanuts.
Over the last few decades, there has been increasing interest in the use of oral immunotherapies for the treatment of peanut allergy. Oral immunotherapy refers to the controlled consumption of increasing amounts of the allergen over time with the goal of inducing desensitisation (i.e. increasing the amount of allergen that is required to cause an allergic reaction in an individual).
AR101 is a peanut derived oral immunotherapy developed by Aimmune Therapeutics. It was approved with the name Palforziaä by the US Food and Drug Administration (FDA) in January 2020 to mitigate allergic reactions after accidental exposure to peanuts in individuals aged 4–17 years with a confirmed diagnosis of peanut allergy.
FDA approval was based, in part, on the results of the PALISADE (Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization in Children and Adults) trial, to which CHI Crumlin and Cork University Hospital had also recruited children, which investigated the safety and efficacy of AR101 in a population of children (aged 4-17 years) and adults with peanut allergy. The trial showed that after 1 year of treatment, participants given AR101 were able to tolerate challenge doses of peanut protein compared to the placebo group.
Currently, AR101 is not approved for clinical use by regulatory bodies outside the US. To build on the results of the PALISADE trial, the ARTEMIS (AR101 Trial in Europe Measuring Oral Immunotherapy Success in peanut allergic children) was done to evaluate the safety and efficacy of AR101 in children and adolescents with peanut allergy in Europe.
Children and adolescents (4-17 years) with a diagnosis of peanut allergy were enrolled and randomly assigned to receive daily doses of either AR101 or a taste-masked placebo. Doses were increased every 2 weeks over 6 months until a dose of 300 mg was reached and maintained for 3 months. At the exit food challenge, participants treated with AR101 were able to tolerate higher doses of peanut compared to the placebo group. AR101 oral immunotherapy was also associated with greater improvements in self-reported and caregiver-reported food allergy-related quality of life.
The ARTEMIS trial was performed across 18 hospitals in Ireland (CHI Crumlin and Cork University Hospital), France, Germany, Italy, Spain, Sweden, and the UK. The NCRC’s Children’s Clinical Research Unit provided support for the ARTEMIS trial at Children’s Health Ireland at Crumlin. The CCRU provides the expertise, dedicated infrastructure and resources required to assist Clinical Teams and Industry Sponsors to conduct clinical research at Children’s Health Ireland (CHI) at Crumlin, and other hospitals across Ireland.
On publication of the ARTEMIS trial results, the CCRU’s programme manager Mary Costello said “This is an excellent example of the importance of conducting clinical trials in children. It is only through clinical trials like this, designed specifically for children, that we can advance children’s medicine and ensure that they can avail of new and improved treatments tailored to their particular needs. Taking part in international studies like this means that we can be part of this ground-breaking research”.
Prof Hourihane commented “These are exciting times in food allergy as international trials, for the first time involving Irish children, are bringing novel therapies to the clinic at a very rapid pace. European licencing applications are being reviewed now. Immunotherapy has a real impact on most children who have been investigated so far but it is hard work, with daily dosing with a product the child has feared before and allergic reactions being actually more common during this “live” treatment. Overall the impacts are positive and substantial. Longer term trials are being written up right now, which will help clinicians and families decide how and when different kinds of therapies are used in individualised careplans”.
The results of the ARTEMIS trial were published in the international peer-reviewed journal “Lancet Child & Adolescent Health”.
The complete publication can be found through the following link:
Jonathan O’B Hourihane, Kirsten Beyer, Allyah Abbas, Montserrat Fernández-Rivas, Paul J Turner, Katharina Blumchen, Caroline Nilsson, Maria D Ibáñez, Antoine Deschildre, Antonella Muraro, Vibha Sharma, Michel Erlewyn-Lajeunesse, José Manuel Zubeldia, Frederic De Blay, Christine D Sauvage, Aideen Byrne, John Chapman, Franck Boralevi, Audrey DunnGalvin, Charmaine O’Neill, David Norval, Andrea Vereda, Ben Skeel, Daniel C Adelman, George du Toit. Efficacy and safety of oral immunotherapy with AR101 in European children with a peanut allergy (ARTEMIS): a multicentre, double-blind, randomised, placebo-controlled phase 3 trial. Lancet Child Adolesc Health. 2020 Jul 20;S2352-4642(20)30234-0 (Pubmed)