Y. King

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

Summary Background Small 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. Methods We 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. Fishers 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. Findings The 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). Interpretation OIT 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 desensitisation. Further studies in wider populations are recommended; peanut OIT should not be done in non-specialist settings, but it is effective and well tolerated in the studied age group. Funding MRC-NIHR partnership.

Successful oral tolerance induction in severe peanut allergy

Background:  Peanut allergy is common, potentially severe and rarely resolves causing impaired quality of life. No disease‐modifying treatment exists and there is therefore a need to develop a therapeutic intervention.

Efficacy and safety of high-dose peanut oral immunotherapy with factors predicting outcome

Background Peanut allergy is severe and rarely resolves.

A longitudinal study of resolution of allergy to well‐cooked and uncooked egg

Background Egg allergy is common and although resolution to uncooked egg has been demonstrated, there is lack of evidence to guide reintroduction of well‐cooked egg.

Patterns of immunoglobulin G responses to egg and peanut allergens are distinct: ovalbumin‐specific immunoglobulin responses are ubiquitous, but peanut‐specific immunoglobulin responses are up‐regulated in peanut allergy

Background The clinical significance of food‐specific IgG subclasses in food allergy and tolerance remains unclear. Specific IgG titres are often reported in non‐standardized units, which do not allow comparisons between studies or allergens.

Facial thermography is a sensitive and specific method for assessing food challenge outcome

Background:  Oral challenge is widely used for diagnosing food allergy but variable interpretation of subjective symptoms may cause error. Facial thermography was evaluated as a novel, objective and sensitive indicator of challenge outcome.

Thermographic imaging during nasal peanut challenge may be useful in the diagnosis of peanut allergy.

Double‐blinded challenges are widely used for diagnosing food allergy but are time‐consuming and cause severe reactions. Outcome relies on subjective interpretation of symptoms, which leads to variations in outcome between observers. Facial thermography combined with nasal peanut challenge was evaluated as a novel objective indicator of clinical allergy.

T cell proliferation and cytokine responses to ovalbumin and ovomucoid detected in children with and without egg allergy.

Background The specific T cell responses in egg allergy and resolution have not been fully elucidated.