Peanut Oral Immunotherapy Threshold Dose for Reactivity: What is the Upper Limit?

RATIONALE: Previous peanut oral immunotherapy (POIT) trials have examined the efficacy of treatment through assessment of the proportion of subjects successfully completing a double blind placebo controlled food challenge (DBPCFC) with up to a cumulative dose of 5000 mg of peanut protein after 3900 mg maintenance dosing. The upper threshold for clinical reactivity after POIT has not been determined.

METHODS: A single center pilot clinical trial of POIT with peanut allergic subjects was performed with a build-up phase to a daily maintenance dose of 3900 mg of peanut protein or highest tolerated dose, over ~48 weeks. Skin prick testing (SPT) was performed at baseline and at maintenance. The upper threshold dose of clinical reactivity was measured with DBPCFC to a cumulative dose of 26,225 mg. A general linear mixed model was used to compare mean challenge reaction doses at baseline versus 1 year.

RESULTS: Of 15 treated subjects, 10 (67%) subjects advanced to maintenance dosing with 9 on 3900 mg daily. Of nine subjects, 8 (89%) reacted to >10,725 mg and 4 (44%) to >15,225 mg (6,725-26,225 mg). The mean cumulative reaction dose at baseline was 149 mg compared with 14,038 mg at maintenance. The mean cumulative reaction dose increased by 13,889 mg (P=0.0001). Median peanut SPT wheal size decreased from 18 to 4 mm (p=0.002).

CONCLUSIONS: POIT with 3900 mg regular maintenance dosing induced clinical desensitization to doses as high as 2-6 times the daily dose amount. The upper threshold dose of clinical reactivity following POIT can be significantly higher than maintenance dosing.