Open-Label Study of the Efficacy, Safety, and Durability of Peanut Sublingual Immunotherapy in Peanut-Allergic Children

Peanut allergy affects 1% to 2% of children. Avoidance is recommended, as accidental exposures may occur and can lead to severe allergic reactions. To decrease this risk, immunotherapy may be a valuable treatment. Few studies have examined the efficacy and safety of peanut sublingual immunotherapy (SLIT) in peanut-allergic children. The authors present their findings on utilization of a new protocol of SLIT particularly focusing on its efficacy, safety, and durability.

The study enrolled 54 challenge-proven peanut allergic children ranging from 1 to 11 years of age (mean 7.1±2.6 years). Most children were male and white. The population was highly atopic, including children with additional food allergies (27.8%), atopic dermatitis (70.4%), allergic rhinitis (59.3%), and/or well-controlled asthma (40.7%).

Patients underwent 3 double-blind-placebo controlled food challenges during study: at start of study, following 48 months of maintenance SLIT, and following predetermined avoidance phase. SLIT therapy was administered daily as measured drops under the tongue for 2 minutes before swallowing. Escalation of doses was performed monthly in clinic or at home to a total of 4 mg peanut protein. Reaction thresholds were determined after each double-blind-placebo controlled food challenges and were reported as successfully consumed dose (SCD). For the avoidance phase, patients who completed 48 months of SLIT and had SCD of 300 mg after the second food challenge, were randomly assigned to 1 to 17 weeks of peanut SLIT avoidance before returning for the last food challenge. Mechanistic studies included skin prick testing and measurement of peanut specific IgE, IgG4, basophil activation test, and T-cell cytokines at baseline, 6, 12, 24, 36, and 48 months of peanut SLIT.

Fifty-four patients were enrolled in the study. Seven patients withdrew and did not complete the 48 month challenge. Forty-seven children (87%) completed SLIT dosing and underwent food challenges at 48 months. Thirty-seven children completed the SLIT avoidance phase. The median successfully consumed dose of peanut increased from 12.5 mg at baseline to 2723 mg following 48 months of maintenance 4 mg SLIT. Of the 47 patients who underwent 48 month DBPCFC, 70% achieved predetermined clinically significant desensitization with SCD >800 mg peanut protein; of which 36% tolerated 5000 mg without reaction. Avoidance of SLIT and repeat food challenges were performed in 37 patients. Calculated time to loss of desensitization depicted utilizing Kaplan Meier survival curves and an SCD <800 mg was 22 weeks. No one reacted at <300 mg peanut protein. Mechanistically, peanut specific IgG4, basophil activation test, wheal diameter, IgE and T-cell cytokines decreased at 6, 6, 12, 24, and 48 months, respectively. This suggests desensitization at the cellular level and supports clinical findings. Dosing compliance was 97.6%. Symptoms were reported after 4% of home administered doses and included local oropharyngeal and lip swelling (3.7%), abdominal symptoms (pain, vomiting, and diarrhea, 0.1%), and lower respiratory symptoms (0.03%). Antihistamines were administered in 0.14% of doses without need for epinephrine. Eosinophilic esophagitis was not diagnosed during this study.

In this cohort of 54 peanut allergic children participating in an open-label prospective peanut SLIT study, 47 completed the 48 month maintenance phase and had notable desensitization. Seventy percent of patients achieved a SCD of at least 800 mg (approx. 0.3–4 peanuts). Patients were compliant with dosing and none required epinephrine. Durability of SLIT following avoidance found that 49% of patients lost at least 1 step at 17 weeks and Kaplan Meier survival curves found the loss of clinically significant desensitization was 22 weeks.

Knowledge of immunotherapy approaches for food allergic patients is important as they may provide protection from accidental exposure to peanut and decrease anaphylaxis risk. Peanut SLIT appears to be a promising therapy in this small cohort of patients. Researchers studied a new approach updosing both at home and in clinic, with well tolerated higher maintenance dose and good desensitization outcomes. Further research is warranted to study the efficacy, safety, and durability in a larger, more heterogeneous population. Additionally, studying the nonresponders or those who did not tolerate SLIT may provide more mechanistic information about peanut allergy and about those who should be considered for other therapies.