There were two phases in this innovative study. In the first phase, participants were randomly assigned to receive either 26 weeks of OIT doses up to 800 mg of peanut protein (given as peanut flour mixed into food in increasing doses from 2mg to 800mg), or to practise peanut avoidance. At the end of 26 weeks, all children underwent a double-blind, placebo-controlled, peanut challenge. In the second phase, the peanut avoidance control group also underwent a 26 week OIT trial. The results of the two phases were impressive: “84% of participants in first phase and 91% in the second phase could tolerate daily ingestion roughly equivalent to five peanuts per day.” Side effects where they occurred in some participants were mild and transient. Only one participant needed adrenaline because of a more serious reaction during the trial.
Raising the peanut reactive threshold to such an extent by OIT has obvious safety gains for these young peanut allergic individuals should they accidentally encounter peanut protein in foodstuffs. Reducing fear and risk of serious reactions also raises quality of life, which was a very important accompanying benefit in this study.
Speaking about the study at the recent International Peanut Forum in Rome, co-investigator Dr. Pamela Ewan said it was important that the design of the Cambridge STOP II trial meant that all children were given the opportunity to have OIT and be challenged for their tolerance to peanut. She highlighted that the children in the control group in the first phase of the study, when put through active treatment in phase two, scored equally well as the initial treatment group. Some of the participants were able to consume up to five peanuts a day up as long as six months after starting treatment. Importantly too, there was considerable improvement in the quality of life scores of these children. The Cambridge team is now investigating whether weekly treatment rather than daily OIT will achieve the same results. At the moment, no one knows what the right stopping point for OIT might be in order to achieve lasting tolerance. That is an issue that must be addressed in further work.
In her IPF presentation, Dr. Ewan also commented on one aspect of the trial that presents a considerable challenge to the government regulatory bodies who will eventually have to licence OIT as a widely available therapy outside of specialist centres. That is the challenge of how to categorize and apply very strict compositional criteria to a foodstuff – peanut flour – which is used as a drug in controlled administration to achieve a clinical effect. This has never been done before and new procedures will be required. While the issue of drug licensing was being addressed, she said, the Cambridge team was embarking on offering OIT treatment on a named patient basis at their clinic later this year with anticipated rolling out to a network of other centres in UK. This was in response to the large numbers of patient seeking OIT treatment for severe peanut allergy.
In an accompanying editorial in The Lancet, peanut allergy expert Dr. Matthew Greenhawt of the University of Michigan praised the design of the Cambridge trial and its “exceptionally promising” results. But he stressed that “It is important to understand that OIT research cannot be rushed, and is years away from routine clinical use. Investigative groups need time to refine protocols, revalidate data, understand the mechanisms of OIT, and minimize adverse effects. This must be done without added pressure or heightened expectations to quickly produce a marketable therapy.
¹ Anagnostou K et al. 2014. “Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial.” Lancet 383: 1297-1304. The study was funded by the UK Medical Research Council and managed by the UK National Institute for Health Research.