Sustained outcomes in oral immunotherapy for peanut allergy (POISED study): a large, randomised, double-blind, placebo-controlled, phase 2 study

• Published in: The Lancet (British edition) 2019-10, Vol.394 (10207), p.1437-1449
• Main Authors: Chinthrajah, R Sharon, Purington, Natasha, Andorf, Sandra, Long, Andrew, O'Laughlin, Katherine L, Lyu, Shu Chen, Manohar, Monali, Boyd, Scott D, Tibshirani, Robert, Maecker, Holden, Plaut, Marshall, Mukai, Kaori, Tsai, Mindy, Desai, Manisha, Galli, Stephen J, Nadeau, Kari C
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adolescent; Allergies; Ara h 2 antigen; Arachis; Asthma; Biomarkers; Child; Clinical trials; Desensitization, Immunologic - adverse effects; Desensitization, Immunologic - methods; Double-Blind Method; Double-blind studies; Female; Flour; Food allergies; Gastrointestinal Diseases - etiology; Gastrointestinal symptoms; Humans; Immunoglobulin E; Immunoglobulin E - blood; Immunoglobulin G; Immunotherapy; Infectious diseases; Legumes; Male; Oral administration; Patients; Peanut Hypersensitivity - diagnosis; Peanut Hypersensitivity - immunology; Peanut Hypersensitivity - therapy; Peanuts; Plant Proteins - administration & dosage; Plant Proteins - adverse effects; Proteins; Randomization; Skin diseases; Skin Tests; Treatment Outcome
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(19)31793-3

Dietary avoidance is recommended for peanut allergies. We evaluated the sustained effects of peanut allergy oral immunotherapy (OIT) in a randomised long-term study in adults and children. In this randomised, double-blind, placebo-controlled, phase 2 study, we enrolled participants at the Sean N Parker Center for Allergy and Asthma Research at Stanford University (Stanford, CA, USA) with peanut allergy aged 7–55 years with a positive result from a double-blind, placebo-controlled, food challenge (DBPCFC; ≤500 mg of peanut protein), a positive skin-prick test (SPT) result (≥5 mm wheal diameter above the negative control), and peanut-specific immunoglobulin (Ig)E concentration of more than 4 kU/L. Participants were randomly assigned (2·4:1·4:1) in a two-by-two block design via a computerised system to be built up and maintained on 4000 mg peanut protein through to week 104 then discontinued on peanut (peanut-0 group), to be built up and maintained on 4000 mg peanut protein through to week 104 then to ingest 300 mg peanut protein daily (peanut-300 group) for 52 weeks, or to receive oat flour (placebo group). DBPCFCs to 4000 mg peanut protein were done at baseline and weeks 104, 117, 130, 143, and 156. The pharmacist assigned treatment on the basis of a randomised computer list. Peanut or placebo (oat) flour was administered orally and participants and the study team were masked throughout by use of oat flour that was similar in look and feel to the peanut flour and nose clips, as tolerated, to mask taste. The statistician was also masked. The primary endpoint was the proportion of participants who passed DBPCFCs to a cumulative dose of 4000 mg at both 104 and 117 weeks. The primary efficacy analysis was done in the intention-to-treat population. Safety was assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02103270. Between April 15, 2014, and March 2, 2016, of 152 individuals assessed, we enrolled 120 participants, who were randomly assigned to the peanut-0 (n=60), peanut-300 (n=35), and placebo groups (n=25). 21 (35%) of peanut-0 group participants and one (4%) placebo group participant passed the 4000 mg challenge at both 104 and 117 weeks (odds ratio [OR] 12·7, 95% CI 1·8–554·8; p=0·0024). Over the entire study, the most common adverse events were mild gastrointestinal symptoms, which were seen in 90 of 120 patients (50/60 in the peanut-0 group, 29/35 in the peanut-300 group, and 11/25 in the placebo group) a