Probiotic peanut oral immunotherapy versus oral immunotherapy and placebo in children with peanut allergy in Australia (PPOIT-003): a multicentre, randomised, phase 2b trial.

BACKGROUND: Oral immunotherapy is effective at inducing desensitisation to allergens and induces sustained unresponsiveness (ie, clinical remission) in a subset of patients, but causes frequent reactions. We aimed to investigate whether addition of a probiotic adjuvant improved the efficacy or safety of peanut oral immunotherapy. METHODS: PPOIT-003, a multicentre, randomised, phase 2b trial, was conducted in three tertiary hospitals in Australia (Adelaide [SA], Melbourne [VIC], and Perth [WA]) in children aged 1-10 years, weighing more than 7 kg, with peanut allergy confirmed by a double-blind placebo-controlled food challenge (cumulative 4950 mg dose of peanut protein) and positive peanut skin prick test (≥3 mm) or peanut-specific IgE (≥0·35 kU/L). Children were randomly assigned (2:2:1) to receive probiotic and peanut oral immunotherapy (PPOIT), placebo probiotic and peanut oral immunotherapy (OIT), or placebo probiotic and placebo OIT (placebo) for 18 months, and were followed up until 12 months after completion of treatment. Oral immunotherapy consisted of increasing doses of peanut protein (commercially available food-grade 12% defatted peanut flour [50% peanut protein]) until a 2000 mg daily maintenance dose was reached. The probiotic adjuvant was a daily dose of 2 × 1010 colony-forming units of the probiotic Lactobacillus rhamnosus ATCC 53103. Placebo immunotherapy comprised maltodextrin, brown food colouring, and peanut essence, and placebo probiotic was maltodextrin. Dual primary outcomes were 8-week sustained unresponsiveness, defined as no reaction to a cumulative dose of 4950 mg peanut protein at treatment completion and 8 weeks after treatment completion, in the PPOIT versus placebo groups and the PPOIT versus OIT groups, analysed by intention to treat. Safety endpoints were adverse events during the treatment phase, and peanut ingestion and reactions in the 12-month post-treatment period. This study is registered with the Australian New Zealand Clinical Trials Registry, 12616000322437. FINDINGS: Between July 4, 2016, and Sept 21, 2020, 201 participants were enrolled and included in the intention-to-treat analysis. 36 (46%) of 79 children in the PPOIT group and 42 (51%) of 83 children in the OIT group achieved sustained unresponsiveness compared with two (5%) of 39 children in the placebo group (risk difference 40·44% [95% CI 27·46 to 53·42] for PPOIT vs placebo, p<0·0001), with no difference between PPOIT and OIT (-5·03% [-20·40 to 10·34], p=0·52). Treatment-related adverse events were reported in 72 (91%) of 79 children in the PPOIT group, 73 (88%) of 83 children in the OIT group, and 28 (72%) of 39 children in the placebo group. Exposure-adjusted incidence of adverse events was 10·58 in the PPOIT group, 11·36 in the OIT, and 2·09 in the placebo group (ratio 0·92 [95% CI 0·85 to 0·99] for PPOIT vs OIT, p=0·042; 4·98 [4·11-6·03] for PPOIT vs placebo, p<0·0001; 5·42 [4·48-6·56] for OIT vs placebo, p<0·0001), with differences seen primarily in gastrointestinal symptoms and in children aged 1-5 years. During the 12-month post-treatment period, 60 (85%) of 71 participants in the PPOIT group, 60 (86%) of 70 participants in the OIT group, and six (18%) of 34 participants in the placebo group were eating peanut; rescue epinephrine use was infrequent (two [3%] of 71 in the PPOIT group, four [6%] of 70 in the OIT group, and none in the placebo group). INTERPRETATION: Both PPOIT and OIT were effective at inducing sustained unresponsiveness. Addition of a probiotic did not improve efficacy of OIT, but might offer a safety benefit compared with OIT alone, particularly in preschool children. FUNDING: National Health and Medical Research Council Australia and Prota Therapeutics.

Can early introduction of egg prevent egg allergy in infants? A population-based study.

BACKGROUND: Infant feeding guidelines have long recommended delaying introduction of solids and allergenic foods to prevent allergy in high-risk infants, despite a paucity of evidence. OBJECTIVE: We aimed to determine whether confirmed egg allergy in 12-month-old infants is associated with (1) duration of breast-feeding and (2) ages of introducing egg and solids. METHODS: In a population-based cross-sectional study (HealthNuts) parents reported on infant feeding and potential confounding factors before skin prick testing for egg white. Egg-sensitized infants were then offered an egg oral food challenge. Multiple logistic regression was used to investigate associations between diet and egg allergy adjusted for possible confounding factors. RESULTS: A total of 2589 infants (73% response) participated. Compared with introduction at 4 to 6 months, introducing egg into the diet later was associated with higher risks of egg allergy (adjusted odds ratios [ORs], 1.6 [95% CI, 1.0-2.6] and 3.4 [95% CI, 1.8-6.5] for introduction at 10-12 and after 12 months, respectively). These findings persisted even in children without risk factors (OR, 3.3 [95% CI, 1.1-9.9]; 10-12 months). At age 4 to 6 months, first exposure as cooked egg reduced the risk of egg allergy compared with first exposure as egg in baked goods (OR, 0.2 [95% CI, 0.06-0.71]). Duration of breast-feeding and age at introduction of solids were not associated with egg allergy. CONCLUSIONS: Introduction of cooked egg at 4 to 6 months of age might protect against egg allergy. Changes in infant feeding guidelines could have a significant effect on childhood egg allergy and possibly food allergy more generally.

Magnetic resonance imaging findings in a population-based cohort of children with cerebral palsy.

The purpose of this study was to investigate the frequency and spectrum of magnetic resonance imaging (MRI) abnormalities in a population of children with cerebral palsy (CP) who were born in the years 2000 and 2001 in Victoria, Australia. In 2000 and 2001, 221 children (126 males, 95 females; mean age 6y [SD 7mo], range 5-7y) with CP, excluding those with CP due to postneonatal causes (6% of all cases), were identified through the Victorian Cerebral Palsy Register. All medical records were systematically reviewed and all available brain imaging was comprehensively evaluated by a single senior MRI radiologist. MRI was available for 154 (70%) individuals and abnormalities were identified in 129 (84%). The study group comprised 88% with a spastic motor type CP; the distribution was hemiplegia in 33.5%, diplegia in 28.5%, and quadriplegia in 37.6% of children. Overall, pathological findings were most likely to be identified in children with spastic hemiplegia (92%) and spastic quadriplegia (84%). Abnormalities were less likely to be identified in non-spastic motor types (72%) and spastic diplegia (52%). The most common abnormalities identified on MRI were periventricular white matter injury (31%), focal ischaemic/haemorrhagic lesions (16%), diffuse encephalopathy (14%), and brain malformations (12%). Dual findings were seen in 3% of patients. This is the first study to document comprehensively the neuroimaging findings of all children identified with CP born over a consecutive 24-month period in a large geographical area.