PURPOSE OF THE STUDY.
To determine the safety and efficacy of sublingual immunotherapy (SLIT) for inducing desensitization in subjects with peanut allergy.
The study population consisted of 40 subjects (ages 12–37 years) from 5 US sites with peanut allergy defined by clinical history or physician diagnosis, positive skin-prick test or peanut-specific immunoglobulin E (Pn-IgE; ≥0.35 kU/L), and a positive double-blind, placebo-controlled oral food challenge (OFC) to ≤2 g of peanut powder. Patients with a history of severe anaphylaxis to peanut were excluded.
Subjects were randomly assigned 1:1 to peanut (Pn) or placebo (Pb) SLIT groups. Subjects started with an initial daily SLIT dose (peanut = 0.000165 μg), with dose escalation every 2 weeks up to a maximum dose of 1386 μg. A 5-g OFC to peanut powder (2.5 g of peanut protein) was conducted at week 44. Subjects in the Pb-SLIT group crossed over to high-dose-peanut SLIT (3696-μg target dose) and received a 5-g OFC after 44 weeks, whereas Pn-SLIT subjects continued dosing until a 10-g OFC at 68 weeks. Responders were defined as those able to consume 5 g of peanut powder or a 10-fold increase over baseline OFC. Total IgE levels, Pn-IgE, Pn-immunoglobulin G4 (IgG4), and basophil activation were monitored at baseline and during the study.
Subjects in the Pn-SLIT group showed a significantly higher response at 44 weeks compared with those in the Pb-SLIT group (70% vs 15%, respectively; P < .001), with a successfully consumed dose (SCD) that was higher in the Pn-SLIT group compared with the Pb-SLIT group (371 vs 21 mg, respectively; P = .01). After 68 weeks of Pn-SLIT, the median SCD further increased to 996 mg (P = .05). The median SCD in the week 44 crossover OFC was higher than baseline (603 vs 71 mg; P = .02). From baseline to week 44, 99.4% of the placebo group was symptom-free compared with 59.9% of the Pn-SLIT group. Pn-IgE and Pn-IgG4 in the Pn-SLIT group increased between baseline and week 44 only (P = .035). No statistical difference in Pn-IgE or Pn-IgG4 was found at week 44 between Pb-SLIT and Pn-SLIT, Pn-SLIT responders and nonresponders, or the crossover high-dose group and the Pn-SLIT group. Basophil activation was significantly lower in the Pn-SLIT group compared with the Pb-SLIT group. The Pn-SLIT responders showed a reduction in skin-prick test compared with nonresponders at week 44 (P = .03).
This study reveals a significant effect of Pn-SLIT in inducing desensitization. During 10 885 doses of Pn-SLIT, 95.3% of subjects were symptom-free at week 44 when oropharyngeal symptoms were excluded.
This was the first multicenter, randomized, placebo-controlled trial to examine SLIT in peanut-allergic subjects. This trial demonstrates a significant degree of desensitization in peanut-allergic subjects by using a treatment with a low side-effect profile. Whereas there are limitations highlighted in this study, this is an important development in therapy for peanut allergies that necessitates further investigation.
- Copyright © 2013 by the American Academy of Pediatrics