Study of induction of Tolerance to Oral Peanut: a randomised controlled trial of desensitisation using peanut oral immunotherapy in children (STOP II)

Abstract

BackgroundPeanut allergy is a common disease that causes severe and fatal food allergic reactions. Currently, the best treatment is avoidance as repeated reactions can occur. Quality of life (QoL) is reduced by fear of severe reactions and social limitations. Oral immunotherapy (OIT) is a novel treatment that may be an effective treatment for peanut allergy.ObjectivesTo determine the efficacy of peanut OIT in children.DesignA phase 2 randomised, controlled, crossover trial (open label).SettingSingle UK centre study.ParticipantsChildren aged 7–15 years with peanut allergy diagnosed by double-blind, placebo-controlled food challenge (DBPCFC). No children were excluded because of anaphylaxis or asthma.InterventionsDaily immunotherapy (2 mg, 5 mg, 12.5 mg, 25 mg, 50 mg, 100 mg, 200 mg, 400 mg and 800 mg of peanut protein) was administered as peanut flour (containing 50% peanut protein). Doses were increased at 2-weekly intervals to a maintenance dose of 800 mg of protein. The control group underwent peanut avoidance for 6 months during phase 1.Main outcome measureA peanut DBPCFC up to 1400 mg of peanut protein was performed in both groups at 6 months. The highest amount of peanut tolerated was the main outcome measure.RandomisationRandomised by online audited system to active or control group (1 : 1).BlindingThe intervention arm allocation was not blinded.MethodsWe assigned 99 participants aged 7–16 years with peanut allergy of all severities to active OIT or control (peanut avoidance/current standard of care). The primary outcome was desensitisation, defined as negative peanut challenge (1400 mg of protein DBPCFC) at 6 months (phase 1). Control participants underwent OIT during phase 2, followed by DBPCFC. Immunological parameters and disease-specific QoL scores were measured.ResultsThe primary outcome, desensitisation, was observed in 62% (24/39) of the active group and none (0/46) of the control group after phase 1 [95% confidence interval (CI) 45% to 78% vs. 0% to 9%;p < 0.001]; 84% (95% CI 70% to 93%) of the active group tolerated daily ingestion of 800 mg of protein (≈ five peanuts). Median increase in peanut threshold after OIT was 1345 mg (range 45–1400 mg;p < 0.001) or 2.5-fold (range 1.82–280-fold;p < 0.001). After phase 2, 54% (95% CI 35% to 72%) tolerated a 1400-mg challenge (≈ 10 peanuts) and 91% (95% CI 79% to 98%) tolerated a daily ingestion of 800 mg of protein. QoL scores improved (decreased) after OIT (median change –1.61;p < 0.001). Side effects were mostly mild with gastrointestinal symptoms being the most common: oral pruritus occurred after 6.3% of doses, wheeze occurred after 0.41% of doses (one-fifth of participants) and intramuscular epinephrine was required after 0.01% of doses (one participant).ConclusionIn children with peanut allergy of any severity, OIT successfully induced desensitisation in the majority, with a clinically meaningful increase in peanut threshold. QoL improved after intervention and there was a good safety profile. Immunological changes reflected clinical desensitisation. Peanut OIT should not be undertaken in non-specialist settings. Future work will include a phase 3 confirmatory study and studies of long-term tolerance; similar studies of other allergens are also required.Trial registrationCurrent Controlled Trials ISRCTN62416244.FundingThis project was awarded by the Efficacy and Mechanism Evaluation programme and is funded by the Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC–NIHR partnership, and jointly sponsored by the University of Cambridge and Addenbrooke’s Hospital [Cambridge University Hospital Foundation Trust (RD authorisation A091686)]. The project will be published in full inEfficacy and Mechanism Evaluation; Vol. 1, No. 4. See the NIHR Journals Library website for further project information.