Sublingual immunotherapy for peanut allergy: a randomized, double-blind, placebo-controlled multicenter trial

Abstract

Background: There are presently no available therapeutic options for patients with peanut allergy.

Objective: We sought to investigate the safety, efficacy, and immunologic effects of peanut sublingual immunotherapy (SLIT).

Methods: After a baseline oral food challenge (OFC) of up to 2 g of peanut powder (approximately 50% protein; median successfully consumed dose [SCD], 46 mg), 40 subjects, aged 12 to 37 years (median, 15 years), were randomized 1:1 across 5 sites to daily peanut or placebo SLIT. A 5-g OFC was performed after 44 weeks, followed by unblinding; placebo-treated subjects then crossed over to higher dose peanut SLIT, followed by a subsequent crossover Week 44 5-g OFC. Week 44 OFCs from both groups were compared with baseline OFCs; subjects successfully consuming 5 g or at least 10-fold more peanut powder than the baseline OFC threshold were considered responders.

Results: After 44 weeks of SLIT, 14 (70%) of 20 subjects receiving peanut SLIT were responders compared with 3 (15%) of 20 subjects receiving placebo (P < .001). In peanut SLIT responders, median SCD increased from 3.5 to 496 mg. After 68 weeks of SLIT, median SCD significantly increased to 996 mg (compared with Week 44, P = .05). The median SCD at the Week 44 Crossover OFC was significantly higher than baseline (603 vs 71 mg, P = .02). Seven (44%) of 16 crossover subjects were responders; median SCD increased from 21 to 496 mg among responders. Of 10,855 peanut doses through the Week 44 OFCs, 63.1% were symptom free; excluding oral-pharyngeal symptoms, 95.2% were symptom free.

Conclusions: Peanut SLIT safely induced a modest level of desensitization in a majority of subjects compared with placebo. Longer duration of therapy showed statistically significant increases in the SCD.

Trial registration: ClinicalTrials.gov NCT00580606.

Figure 1. Enrollment and Disposition of Subjects

The 40 subjects who passed screening were randomized onto placebo or peanut SLIT. After the Week 44 oral food challenge, the study was unblinded. Subjects in the original Peanut SLIT group continued on maintenance peanut SLIT therapy and received a Week 68 oral food challenge. Original placebo recipients were offered a higher dose peanut SLIT from week 44 to week 88, and then an oral food challenge.

Figure 2. Oral Food Challenge Successfully Consumed Dose by Treatment Group

Oral food challenge doses successfully consumed were compared to initial 2g baseline successfully consumed doses after 44 weeks of therapy from study entry for randomized, initially treated group; and after 44 weeks of therapy from crossover initiation for Crossover High Dose group. The median oral food challenge successfully consumed dose at Week 44 was significantly higher than at baseline oral food challenge for Peanut SLIT subjects (21mg vs 371mg; p=0.01) but was not for Placebo subjects (71mg vs 146mg; p=0.14). Star identifies the median.

Figure 3. Oral Food Challenge Successfully Consumed Dose for Peanut SLIT Subjects Who Have Week 68 Oral Food Challenge

The oral food challenge successfully consumed doses of subjects are shown by the oral food challenge doses successfully consumed at Baseline, Week 44 and Week 68 for Peanut SLIT subjects. At Week 68, the median dose successfully consumed increased to 996 mg, and this was significantly higher than at Week 44 (p=0.05) and at Baseline (p=0.009). Star identifies the median.

Figure 4. Change in Peanut-Specific IgG4 During SLIT

Levels were compared after 44 weeks of therapy from study entry for the randomized, initially treated group; and after 44 weeks of therapy from crossover initiation for the Crossover High Dose group. Median increase in PN-IgG4 from baseline to Week 44 was statistically significantly higher Crossover High Dose subjects (p<0.001) and in Peanut SLIT compared to placebo (0.3 mg_A/L vs 0.0 mg_A/L; p<0.001). Star identifies the median.