Children aged 4 to 18 years, with peanut allergy (as defined below), were recruited from the Allergy Outpatient Clinic, Department of Paediatrics, National University Hospital, Singapore.

They were excluded if they had history of anaphylaxis, presence of severe or uncontrolled asthma (defined as previous intensive care unit admissions/intubations, or increasing doses of inhaled corticosteroids needed to control asthma, or peak expiratory flow/spirometry values less than 70% of normal), comorbidities which could preclude them from undergoing an OFC, current use of medications which may interfere with treatment of a severe reaction, or inability to comply with the desensitisation protocol.

At visit 1, all subjects underwent a baseline OFC to peanut protein in the form of partially defatted peanut flour (12% fat light roast; Golden Peanut Co., Alpharetta, GA, USA; 2-g flour = 1-g peanut protein). The dose steps (in peanut protein dose) were: 0.5, 1, 2, 5, 12, 25, 50, 100, 200, 400, 800, 1,600, 3,000. The interval between doses was 2 weeks, and the doses were increased until the maintenance dose of 3,000-mg peanut protein was reached. The first OFC was at 6 months into the maintenance phase (visit 2). After completion of treatment, subjects reverted to strict peanut avoidance for 4 weeks and then attended visit 3 to undergo second OFC (Fig. 1).

All subjects also took daily intake of 2 × 10¹⁰ Lactobacillus rhamnosus GG (ATCC 53103) as an adjuvant during the maintenance phase. This recommendation follows the findings of improved efficacy and possible sustained unresponsiveness in a peanut OIT schedule which included Lactobacillus rhamnosus GG as an adjuvant [5].

The primary outcomes were efficacy and safety.

Major peanut allergen-specific IgE and IgG₄ levels were measured in the subjects' plasma samples using ImmunoCAP 100 instrument (Phadia AB, Uppsala, Sweden) according to the manufacturer's instructions. These included peanut extract, Ara h 1, Ara h 2, Ara h 3, Ara h 8 and Ara h 9. Blood was taken for these at baseline before starting peanut OIT (visit 1), 2 weeks after tolerating maintenance therapy (visit 2) and 4 weeks after discontinuation of peanut OIT (visit 3). SPTs (Greer Lab, Allergy Management) (SPTs) to peanut were also performed at these 3 visits.

At the same 3 visits, QoL was assessed using age-specific and validated QoL questionnaires: Food Allergy Quality of Life Questionnaire – Parent Form (FAQLQ-PF) for parents of children aged below 12 years of age, Food Allergy Quality of Life Questionnaire – Child Form (FAQLQ-CF) for children aged 8–12 years, and Food Allergy Quality of Life Questionnaire – Teenager Form (FAQLQ-TF) for adolescents aged 13–17 years [678]. These were scored out of a total of 6 for FAQLQ-PF and CF, and out of 7 for FAQLQ-TF.

Ethical approval was granted by the Domain Specific Review Board, National Healthcare Group number 2013/00672. Informed consent was sought from all parents, with assent from the children as appropriate.

Sixty-eight patients were screened for recruitment, of which, 11 were eligible. Two declined to participate hence 9 patients were recruited between December 2013 and January 2015. The median age of the patients was 8 years (range, 8–14 years); 2 were female. There were 3 Chinese patients, 2 Eurasian, and 4 Caucasian. The median baseline SPT wheal size to peanut extract was 15 mm (range, 8–25 mm), and specific IgE to peanut was 29.35 kU_A/L for 4 patients and above the laboratory upper limit of measurement (>100 kU_A/L) for 5 patients. Five patients had concomitant food allergies or other atopic diseases. The other food allergies included egg, seafood and garlic. The median starting dose of peanut protein for OIT was 5 mg (range, 0.5–50 mg) (Table 1).

Seven of the 9 patients completed the OIT protocol. One subject withdrew almost immediately after enrolment due to noncompliance, and the other subject withdrew soon after the start of the maintenance phase due to the amount of psychological burden the child suffered from ingesting peanuts. The proportion of missed doses was 0.26%.

Of the 7 who completed OIT, 6 tolerated 6,000 mg of peanut protein at the first OFC at 6 months of maintenance phase; the last patient was afraid of consuming more than 3,000 mg of peanut protein but passed the challenge with 3,000 mg. After 12 months of maintenance therapy, only 3 of the 7 subjects consented to 4 weeks of abstinence. Of these, only 1 passed the challenge with 6,000 mg of peanut protein. The threshold of peanut protein tolerated decreased from 6,000 mg at first OFC to 3,690 mg for subject 3, and from 6,000 mg to 257 mg for subject 9 (Table 1).

The median frequency of side effects was 12% (range, 2.9%–28.5%) out of all doses taken during the updosing phase which decreased to 1.65% (range, 0%–18.8%) during the maintenance phase. The most frequent side effects involve the gastrointestinal system (65.7% of all side effects during updosing phase and 47.9% during maintenance phase), especially transient abdominal cramps, followed by skin in the form of urticarial or itch (Fig. 2). Less frequent were upper respiratory, lower respiratory, oral and eye-related. Skin manifestations include rash and angioedema, upper respiratory tract symptoms include rhinitis and cough, lower respiratory tract symptom refers to wheeze, gastrointestinal symptoms include abdominal pain and vomiting, and cardiovascular symptoms include palpitations and dizziness. All side effects were mild, with no incident of anaphylaxis attributable to peanut OIT during treatment.

Side effects occurred more frequently during the first week after an updosing compared to the second week (58% reduction, p < 0.05). They were also most commonly associated with intercurrent illness. Other contributory factors included lack of sleep, missing the previous daily dose, taking a hot bath just before ingestion of the daily dose and in 1 instance, just after an episode of anaphylaxis due to accidental ingestion of another food that the subject was known to be allergic to.

There was a significant change in the median SPT wheal size to peanut extract, from 13 mm at baseline to 4 mm at visit 2 (p < 0.05), and 5 mm at visit 3 (p < 0.05).

There was a trend towards lower specific IgE to peanut extract, Ara h 1, Ara h 2, and Ara h 3 between visits 1 and 3 (Fig. 3). There were no differences in specific IgE to Ara h 8 and Ara h 9 (data not shown).

There was an increase of peanut extract, Ara h 1, Ara h 2, and Ara h 3-specific IgG₄ in the subjects' plasma from visit 1 to visit 2 (p < 0.05), but not between visits 2 and 3. There were no differences in Ara h 8 and Ara h 9-specific IgG₄ between all visits (data not shown).

Seven parents of children aged below 12 years completed the FAQLQ-PF at baseline and visit 2, and 5 at visit 3 (one withdrew and one was lost to follow up). Five children between 8 to 12 years of age completed the FAQLQ-CF and one 14-year-old patient completed the FAQLQ-TF at all 3 visits. The median baseline scores were 3.8, 4.1, and 7 out of a maximal possible 7 for PF, CF, and TF respectively.

At the end of OIT at visit 3, there was a trend towards improving QoL scores, with FAQLQ-PF scores decreasing by 0.5 (n = 5), FAQLQ-CF scores increasing by 0.1 (n = 5) and FAQLQ-TF score decreasing by 0.6 (n = 1).

The patients were followed up for 2–3 years after the end of their peanut OIT. Of the 5 patients who were still in contact with the study team at the time of manuscript preparation, 4 were still consuming peanuts regularly at a dose that was acceptable to the child.