A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy - PubMed
Clinical Trial
A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy
Satya D Narisety et al. J Allergy Clin Immunol. 2015 May.
Abstract
Background: Although promising results have emerged regarding oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) for the treatment of peanut allergy (PA), direct comparisons of these approaches are limited.
Objective: This study was conducted to compare the safety, efficacy, and mechanistic correlates of peanut OIT and SLIT.
Methods: In this double-blind study children with PA were randomized to receive active SLIT/placebo OIT or active OIT/placebo SLIT. Doses were escalated to 3.7 mg/d (SLIT) or 2000 mg/d (OIT), and subjects were rechallenged after 6 and 12 months of maintenance. After unblinding, therapy was modified per protocol to offer an additional 6 months of therapy. Subjects who passed challenges at 12 or 18 months were taken off treatment for 4 weeks and rechallenged.
Results: Twenty-one subjects aged 7 to 13 years were randomized. Five discontinued therapy during the blinded phase. Of the remaining 16, all had a greater than 10-fold increase in challenge threshold after 12 months. The increased threshold was significantly greater in the active OIT group (141- vs 22-fold, P = .01). Significant within-group changes in skin test results and peanut-specific IgE and IgG4 levels were found, with overall greater effects with OIT. Adverse reactions were generally mild but more common with OIT (P < .001), including moderate reactions and doses requiring medication. Four subjects had sustained unresponsiveness at study completion.
Conclusion: OIT appeared far more effective than SLIT for the treatment of PA but was also associated with significantly more adverse reactions and early study withdrawal. Sustained unresponsiveness after 4 weeks of avoidance was seen in only a small minority of subjects.
Keywords: Peanut allergy; food allergy; immunotherapy; oral immunotherapy; sublingual immunotherapy.
Copyright © 2014 American Academy of Allergy, Asthma & Immunology. All rights reserved.
Figures

Consort diagram. Time points include T1 (baseline), T3 (end of dose build up), T4 and T5 (post 6 and 12 months of maintenance, subjects unblinded at T5), T6 (completion of additional 6 months of maintenance), and T7 (4 weeks off therapy).

Change in cumulative OFC dose after SLIT (A) and OIT (B). Red lines indicate active SLIT, blue lines indicate active OIT, and purple lines represent combined SLIT and OIT after unblinding. Open circles represent subjects with sustained unresponsiveness. Between groups, there were significantly greater changes in OFC threshold with OIT compared to SLIT (p=0.008 and p=0.01 after 6 and 12 months of maintenance).

Change in cumulative OFC dose after SLIT (A) and OIT (B). Red lines indicate active SLIT, blue lines indicate active OIT, and purple lines represent combined SLIT and OIT after unblinding. Open circles represent subjects with sustained unresponsiveness. Between groups, there were significantly greater changes in OFC threshold with OIT compared to SLIT (p=0.008 and p=0.01 after 6 and 12 months of maintenance).

Change in endpoint skin test results after SLIT (A) and OIT (B). Red lines indicate active SLIT, blue lines indicate active OIT, and purple lines represent combined SLIT and OIT after unblinding. Open circles represent subjects with sustained unresponsiveness. Comparison of the SLIT and OIT groups revealed similar changes in skin test results over time, with the exception of greater changes in the OIT group at T4 (P=0.03).

Change in endpoint skin test results after SLIT (A) and OIT (B). Red lines indicate active SLIT, blue lines indicate active OIT, and purple lines represent combined SLIT and OIT after unblinding. Open circles represent subjects with sustained unresponsiveness. Comparison of the SLIT and OIT groups revealed similar changes in skin test results over time, with the exception of greater changes in the OIT group at T4 (P=0.03).

Change in peanut-specific IgE after SLIT (A) and OIT (B). Red lines indicate active SLIT, blue lines indicate active OIT, and purple lines represent combined SLIT and OIT after unblinding. Open circles represent subjects with sustained unresponsiveness. By 6 months, the decrease in peanut IgE was greater in the OIT group, and this difference widened by 12 months (p=0.07, p=0.007, respectively).

Change in peanut-specific IgE after SLIT (A) and OIT (B). Red lines indicate active SLIT, blue lines indicate active OIT, and purple lines represent combined SLIT and OIT after unblinding. Open circles represent subjects with sustained unresponsiveness. By 6 months, the decrease in peanut IgE was greater in the OIT group, and this difference widened by 12 months (p=0.07, p=0.007, respectively).

Change in peanut-specific IgG4 after SLIT (A) and OIT (B). Red lines indicate active SLIT, blue lines indicate active OIT, and purple lines represent combined SLIT and OIT after unblinding. Open circles represent subjects with sustained unresponsiveness. Between groups, there was overall a greater change from baseline in peanut-specific IgG4 values over time in the OIT group compared to the SLIT group at all time points [end of dose build up (p=0.003), after 6 and 12 months of maintenance (p<0.001)].

Change in peanut-specific IgG4 after SLIT (A) and OIT (B). Red lines indicate active SLIT, blue lines indicate active OIT, and purple lines represent combined SLIT and OIT after unblinding. Open circles represent subjects with sustained unresponsiveness. Between groups, there was overall a greater change from baseline in peanut-specific IgG4 values over time in the OIT group compared to the SLIT group at all time points [end of dose build up (p=0.003), after 6 and 12 months of maintenance (p<0.001)].
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