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Two Peanut Allergy Treatments for Children Found to Be Highly Effective at Inducing Remission

AHA Publisher — Wed, 09 Feb 2022 08:00:08 +0000

Murdoch Childrens Research Institute via News-Medical – Researchers have discovered two peanut allergy treatments for children that are both highly effective at inducing remission. The research, led by the Murdoch Children’s Research Institute (MCRI), found the treatments – a combination of a probiotic together with oral immunotherapy (the gradual introduction of the allergenic food) and oral immunotherapy alone – significantly induced remission and desensitization. About half of the children achieved remission, allowing them to stop treatment and safely eat peanut freely. Both treatments also provided substantial improvement in quality of life compared with current standard care. The randomized controlled trial conducted at The Royal Children’s Hospital in Melbourne, Perth Children’s Hospital, and the Women’s and Children’s Hospital in Adelaide involved 201 children aged between 1-10 years. The trial was staged over four years, with participants followed up to 12-months post-treatment. The team led by MCRI Professor Mimi Tang had previously shown that the combination treatment resulted in 74 per cent achieving remission after 18 months of treatment, and 70 per cent of those initial responders remained in remission and were eating peanut safely four years later. The next step was to test whether adding a probiotic gave a benefit over and above oral immunotherapy on its own and to compare long-term outcomes following treatment. The new research, published in The Lancet Child & Adolescent Health, found after 18 months of treatment, 46 per cent and 51 per cent of children who received the combination treatment or the oral immunotherapy alone, respectively, were in clinical remission compared to 5 per cent in the placebo group. The children who reached clinical remission were able to stop treatment and eat around a standard serve of peanut freely. Both treatments also led to a significant improvement in quality of life, with those children who achieved clinical remission experiencing the biggest improvement, greater than those who only achieved desensitization. “The results show that high dose peanut oral immunotherapy provides meaningful benefit to treated children. After 18 months of treatment, 74 per cent of children who received the oral immunotherapy tolerated roughly a standard serve of peanut, equal to a snack pack of peanut M&Ms, 51 per cent achieved clinical remission and were able to stop treatment altogether, while the remaining 24 per cent were desensitized to this amount of peanut. “Addition of a probiotic did not significantly improve effectiveness compared to oral immunotherapy, however it appeared to enhance tolerability of the treatment, with fewer gastrointestinal symptoms, especially in children between one and five years of age.” (Mimi Tang, MCRI Professor) The results also showed that treatment with oral immunotherapy, with or without a probiotic for childhood peanut allergy, provides a significant and substantial improvement in quality of life compared with current standard care, which is peanut avoidance. MCRI Dr Paxton Loke said remarkably 99 per cent of children who achieved remission and ceased treatment were eating peanut as frequently as they liked in the 12 months after stopping treatment. “Children who were in clinical remission had fewer reactions to peanut compared with those who were just desensitized,” he said. “Being desensitized still requires continued daily treatment and allergen avoidance so remission appears to be a better outcome for children. Importantly, children in remission had a significantly improved quality of life compared with allergic children, suggesting that no longer having to avoid peanut provides greater benefit than continued allergen avoidance despite the risk of a possible reaction.” The peanut oral immunotherapy approach used in the trial applies a proprietary high dose, rapid escalation regimen that is being developed by Prota Therapeutics as a lead candidate for the treatment of peanut allergy, PRT120. Prota Therapeutics is an Australian biotech company, focused on bringing its allergy immunotherapy treatment for children with life-threatening peanut allergies to market. Melbourne’s Kate Lawlor’s son Declan, 9, who took part in the trial, is now in clinical remission and eats peanuts weekly. Declan was diagnosed with a peanut allergy at age four after having a reaction to peanut butter. Kate said it was a huge relief that her son could now eat peanut freely without fear of a reaction or having to avoid the nut for the rest of his life. “Having a child with a food allergy is quite stressful,” she said. In the home you can control the environment around food but school, play dates and birthday parties are largely out of your hands.” “With Declan now in remission a lot of anxiety has been lifted and he is enjoying eating peanut chocolate M&Ms. He sees this as a real treat and looks forward to eating them every week.” Peanut allergies are the most common cause of severe allergic reactions, called anaphylaxis, and one of the most frequent causes of death from food allergy. About 3 per cent of babies have a peanut allergy. “As there is currently no cure, patients must adhere to strict allergen avoidance, which leads to psychological distress and reduced quality of life,” Professor Tang said. “There is a need for disease modifying therapies that improve health and well-being and both the combination and standalone immunotherapy treatments provided a meaningful benefit. The combination therapy in particular could offer a safe and well tolerated approach to inducing clinical remission in young pre-school children with peanut allergies. Starting treatment early seems to increase the chances of achieving remission and pre-school children are especially vulnerable, so a treatment that causes fewer side effects brings an important advantage.” Researchers from The Royal Children’s Hospital, Monash Children’s Hospital, University of Melbourne, University of Adelaide, Women’s and Children’s Hospital in Adelaide, Perth Children’s Hospital, The University of Western Australia, Telethon Kids Institute, Monash University and University College Cork in Ireland also contributed to the study. To read the original article click here.

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FDA Approves Peanut Allergy Treatment for Children and Teens

AHA Publisher — Fri, 21 Feb 2020 08:00:38 +0000

University of Chicago Medical Center via Newswise – The immunotherapy drug for children and teens is also the first ever food allergy treatment approved by the FDA. Newswise — The University of Chicago Medicine was part of a landmark clinical trial that led to approval by the U.S. Food and Drug Administration of the first oral immunotherapy treatment for peanut allergy in children and teens. Peanuts are among the most common food allergies, affecting an estimated 1.6 million children in the United States, according to a 2018 study published in the journal Pediatrics. Palforzia, manufactured by Aimmune Therapeutics Inc., should significantly reduce the severity of allergic reactions, including anaphylaxis, after accidental peanut exposure. “The patients I treated have universally expressed relief that they no longer have to live in constant fear that one wrong bite of something with peanuts will result in an emergency injection of epinephrine,” said Christina Ciaccio, MD, MSc, UChicago Medicine associate professor of pediatrics and medicine and the site’s principal investigator. Ciaccio administered the treatment as part of a 2018 clinical trial funded by Aimmune Therapeutics. During the trial, patients at sites, including at UChicago Medicine Comer Children’s Hospital, received the treatment. The research was conducted in 10 countries across North America and Europe. “I cannot emphasize enough what a game-changer it will be for both food allergy practitioners and patients to have an FDA-approved product to effectively treat peanut allergy,” Ciaccio said. “To date, we have not been able to do anything but tell patients to carefully monitor what they are eating and to always be prepared with an epinephrine autoinjector in case a reaction does occur.” Aimmune Therapeutics has not yet announced when PALFORZIA will be available to patients. To read the original article click here.

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Researchers Identify Novel Genes Associated With Severity of Peanut Allergy

AHA Publisher — Fri, 20 Dec 2019 08:31:02 +0000

The Mount Sinai Hospital / Mount Sinai School of Medicine via News-Medical Net – Researchers at the Icahn School of Medicine at Mount Sinai have identified novel genes associated with the severity of peanut allergy, as well as ways in which these genes interact with other genes during allergic reactions. The findings, published December 12 in the Journal of Allergy and Clinical Immunology, could lead to better treatments for peanut allergy. Peanut allergy varies widely in severity and is the leading cause of fatal food-related anaphylaxis. The tests used to determine the existence of a peanut allergy don’t offer any clues as to whether an individual ingesting a peanut could experience a minor rash, major swelling, or life-threatening issues such as difficulty breathing or cardiovascular complications. The study’s senior author, Supinda Bunyavanich, MD, MPH, Associate Professor of Genetics and Genomic Sciences, and Pediatrics, and Associate Director of the Elliot and Roslyn Jaffe Food Allergy Institute at Mount Sinai, was especially curious about why the severity of reactions varies so much, both as a clinician-scientist and as a mother of a child with a peanut allergy. To help address this question, Dr. Bunyavanich and her team used novel multi-omic approaches (the study of the role, relationships, and actions of a system-wide measure of a given molecular type) to identify genes and networks of activity that might be driving the severity of peanut allergy reactions. The approaches included transcriptomics, the study of gene expression across the genome, and epigenomics, the study of reversible modifications to DNA that affect gene expression. The study involved 21 children ages 7-17 with peanut allergy, who were given gradually increasing doses of peanut until they displayed an allergic response. The scientists drew blood from the participants at three times: before they ate, as they reacted, and after their reaction. The team confirmed their findings from the initial cohort by repeating the study in another 19 children. Taking blood samples at multiple times allowed the team to analyze both the transcriptome and epigenome (which can tell scientists which genes are turned on or off through a process called methylation) as the children reacted. Using this genome-wide approach, they identified more than 300 genes and 200 CpG sites (areas where DNA can be activated or inactivated by methylation) associated with reaction severity. Combining these data using integrative networks, the team also characterized key interactions between gene expression, CpG sites, and reaction severity. Not only did they identify novel genes associated with the severity of peanut allergy, but they also managed to characterize ways in which these genes interact with other genes and CpG sites during allergic reactions to regulate biological processes. “It was very exciting to apply multi-omics to uncover how genes and methylation sites interact to affect reaction severity in these peanut allergic kids,” says Anh Do, PhD, lead author of the study and postdoctoral fellow in the Bunyavanich Lab. Among the insights is that while the findings support recognized roles for adaptive immunity in allergy, they also suggest that neutrophil (a type of white blood cell)-mediated immunity plays a prominent role in reaction severity. “We know neutrophil-mediated immunity is part of immune responses, and this study suggests it may play a central role in the severity of peanut allergic reactions.” Dr. Supinda Bunyavanich, study’s senior author Additionally, one of the reaction severity drivers the team identified, the gene ARG1, can be inhibited by arginase inhibitors, a type of drug under study for many diseases. This study’s finding suggests it may be a potential target for treating peanut allergy as well. Dr. Bunyavanich hopes future studies will identify biomarkers that can predict who is likely to have severe responses without having to expose them to peanuts first. But in the meantime, she states that this study “hopefully challenges people to think about food allergy with a broader lens.” To read the original article click here.

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