Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial

Abstract

SummaryBackgroundSmall studies suggest peanut oral immunotherapy (OIT) might be effective in the treatment of peanut allergy. We aimed to establish the efficacy of OIT for the desensitisation of children with allergy to peanuts.MethodsWe did a randomised controlled crossover trial to compare the efficacy of active OIT (using characterised peanut flour; protein doses of 2–800 mg/day) with control (peanut avoidance, the present standard of care) at the NIHR/Wellcome Trust Cambridge Clinical Research Facility (Cambridge, UK). Randomisation (1:1) was by use of an audited online system; group allocation was not masked. Eligible participants were aged 7–16 years with an immediate hypersensitivity reaction after peanut ingestion, positive skin prick test to peanuts, and positive by double-blind placebo-controlled food challenge (DBPCFC). We excluded participants if they had a major chronic illness, if the care provider or a present household member had suspected or diagnosed allergy to peanuts, or if there was an unwillingness or inability to comply with study procedures. Our primary outcome was desensitisation, defined as negative peanut challenge (1400 mg protein in DBPCFC) at 6 months (first phase). Control participants underwent OIT during the second phase, with subsequent DBPCFC. Immunological parameters and disease-specific quality-of-life scores were measured. Analysis was by intention to treat. Fisher's exact test was used to compare the proportion of those with desensitisation to peanut after 6 months between the active and control group at the end of the first phase. This trial is registered with Current Controlled Trials, number ISRCTN62416244.FindingsThe primary outcome, desensitisation, was recorded for 62% (24 of 39 participants; 95% CI 45–78) in the active group and none of the control group after the first phase (0 of 46; 95% CI 0–9; p<0·001). 84% (95% CI 70–93) of the active group tolerated daily ingestion of 800 mg protein (equivalent to roughly five peanuts). Median increase in peanut threshold after OIT was 1345 mg (range 45–1400; p<0·001) or 25·5 times (range 1·82–280; p<0·001). After the second phase, 54% (95% CI 35–72) tolerated 1400 mg challenge (equivalent to roughly ten peanuts) and 91% (79–98) tolerated daily ingestion of 800 mg protein. Quality-of-life scores improved (decreased) after OIT (median change −1·61; p<0·001). Side-effects were mild in most participants. Gastrointestinal symptoms were, collectively, most common (31 participants with nausea, 31 with vomiting, and one with diarrhoea), then oral pruritus after 6·3% of doses (76 participants) and wheeze after 0·41% of doses (21 participants). Intramuscular adrenaline was used after 0·01% of doses (one participant).InterpretationOIT successfully induced desensitisation in most children within the study population with peanut allergy of any severity, with a clinically meaningful increase in peanut threshold. Quality of life improved after intervention and there was a good safety profile. Immunological changes corresponded with clinical d...

Oral Immunotherapy for Food Allergy

“…The authors demonstrated a significant increase in the peanut challenge threshold, with 86% of patients tolerating up-dosing and 14/22 (64%) tolerating 6.6 g of peanut protein at the completion of treatment. In 2014, the same group completed a randomized controlled trial (RCT) with peanut OIT at a maintenance dose of 800 mg [23]. In the first phase, each arm underwent 26 weeks of peanut OIT versus peanut avoidance, after which patients underwent a food challenge to 1400 mg of peanut protein.…”

“…Wasserman et al [62] reported that 95 reactions requiring epinephrine occurred during peanut OIT in 352 patients. It is especially concerning that most severe reactions occur unpredictably, with a dose that has previously been tolerated, and that they are often associated with cofactors such as infection, exercise, anxiety, or allergen coexposure [19,23,42,43].…”

Allergenicity attributes of different peanut market types

“…Unfortunately there is no treatment currently available to cure peanut allergy and therefore, peanut-allergic patients must avoid consuming peanut. Several experimental immunotherapies such as oral immunotherapy (Anagnostou et al, 2014;Varshney et al, 2011), sublingual immunotherapy (Burks et al, 2015;Fleischer et al, 2013), and epicutaneous immunotherapy show promising results for desensitizing peanut-allergic patients, although complete tolerance to peanut using these approaches appears to occur in only a limited number of patients. A new approach using modified peanut allergens (Bencharitiwong et al, 2015) for subcutaneous immunotherapy is also currently being investigated (ClinicalTrials.gov identifier NCT02163018).…”

Recent advances in food allergy

“…On the same desensitisation route, the group in Addenbrooke in Cambridge have successfully induced desensitization in children with different degrees of severity to peanut allergy. The peanut Oral Immune therapy (OIT) used was able to raise the reactive threshold to at least 25 times, and in some cases almost 90% of the participants could tolerate the daily ingestion of up to 800 mg protein (ANAGNOSTOU et al, 2014). A recent development widely discussed in the 2015 EAACI meeting refers to the use of epicutaneous immunotherapy (EPIT).…”