Article highlights
- A study explored peanut SLIT in children aged 1 to 4 years to alleviate peanut allergies, which significantly impact their quality of life.
- Conducted at UNC and UTSW, the double-blind, placebo-controlled study enrolled 50 participants, randomized to receive peanut SLIT or placebo SLIT, assessing desensitization and remission rates.
- Peanut SLIT participants showed significant improvement, reaching a median cumulative tolerated dose (CTD) of 4443 mg at 36 months, while the placebo group's CTD was 143 mg, demonstrating desensitization and remission.
- Younger children (1-2 years) demonstrated higher desensitization and remission rates, emphasizing the importance of early intervention.
- The study suggests that peanut SLIT is a safe and effective method for desensitizing and achieving remission in young children with peanut allergies.
The primary outcome of desensitization and remission using peanut sublingual immunotherapy (SLIT) in children aged 1 to 4 years was observed in a study recently published in The Journal of Allergy and Clinical Immunology.
Developing early in life, peanut allergy affects approximately 1% to 2% of children in Western nations, requiring vigilance to avoid ingestion. This vigilance, combined with anxiety and social isolation, can be a significant burden for patients and their families, often leading to a decreased quality of life.
Investigators designed a multicenter, double-blind, randomized, placebo-controlled study (NCT02304991) of peanut SLIT for 36 months in peanut-allergic children aged 1 to 4 years. The study was conducted at the University of North Carolina (UNC) and the University of Texas Southwestern (UTSW). A positive reaction during a double-blind, placebo-controlled food challenge (DBPCFC) to 1000 mg peanut protein was required to be randomized.
A history of severe anaphylaxis to peanut defined as hypoxia, hypotension, or neurologic compromise, eosinophilic or other inflammatory gastrointestinal disease, along with severe asthma were key exclusion criteria.
Individuals were randomly assigned (1:1) to receive the study drug with either peanut SLIT or placebo SLIT. Oat flour was used as a placebo during DBPCFC. Liquid peanut extract (5000 mg/mL peanut protein) from Greer Laboratories made up the study drug. Pure glycerinated saline solution with an added caramel coloring comprised the placebo SLIT.
At entry of the DBPCFC, all participants underwent a 1000 mg cumulative challenge; 6 doses (3, 10, 30, 100, 300, and 557 mg peanut protein) administered 10 to 20 minutes apart. Oat flour in the placebo group was administered in identical doses by weight. At month 36, the DBPCFC was performed to a cumulative dose of 4443 mg, and administered in 7 doses (3, 10, 30, 100, 300, 1000, and 3000 mg). At the 36-month DBPCFC, participants with a cumulative tolerated dose (CTD) of at least 443 mg were instructed to stop the study drug and continue peanut avoidance for 3 months. To assess for remission, a final month 39 DBPCFC was conducted. If the participant ingested all doses and completed 2 hours of observation without meeting stopping criteria, the DBPCFC was scored as a pass.
Desensitization, defined as, “a statistically significant difference in cumulative CTD during DBPCFC at month 36 for peanut SLIT participants versus placebo participant,” was the primary outcome of the study. Median CTD after treatment and the proportion of individuals passing the month 36 DBPCFC after treatment was an additional analysis of the primary endpoint. The proportion of participants that experienced remission (passed month 39 DBPCFC after avoidance period and longitudinal changes in immune markers) was a secondary outcome.
All individuals that initiated the study drug dosing made up the intent-to-treat (ITT) population while those who completed the DBPCFC at month 36 made up the per protocol (PP) population.
Fifty participants (40 at UNC), of which 44% were female, were enrolled in the study with a mean age of 2.4 years. There were 25 participants in the peanut SLIT group and 25 in the placebo SLIT group. At baseline, median CTD was 143 mg (43-143) for peanut SLIT individuals and 43 mg (43-143) for placebo individuals.
The study authors noted that the primary outcome of the study was met by comparison of hazard of failure across food challenge doses (P < .001) and by comparison of the median CTD for peanut SLIT participants (4443 mg, dose 7) compared to placebo participants (143 mg, dose 4) at the 36-month DBPCFC (P < .0001). By ingesting the full 4443 mg of peanut protein without dose-limiting, 15 peanut SLIT participants (ITT 60%, PP 7839%) passed the month 36 DBPCFC compared to 0 placebo participants (P < .0001). At the month 39 DBPCFC, 12 peanut SLIT participants (ITT 48%, PP 63%) passed and demonstrated remission compared to 0 placebo participants (P = .0005).
Median CTD for peanut SLIT individuals increased from 143 mg at baseline to 4443 mg at month 36 (P < .0001). Treated individuals had a higher likelihood of passing the month 36 DBPCFC compared to placebo (60% vs 0), and a higher likelihood of demonstrating remission (48% vs 0). Desensitization and remission rates were highest in 1-to-2-year-old children, followed by 2-to-3-year-olds, and 3-to-4-year-olds.
Investigators concluded the peanut SLIT “safely induces desensitization and remission in 1-to-4-year-old children, with improved outcomes seen with younger age at initiation.”
Reference:
Kim EH, Bird JA, Keet CA, et al. Desensitization and remission after peanut sublingual immunotherapy in 1- to 4-year-old peanut-allergic children: A randomized, placebo-controlled trial. The Journal of Allergy and Clinical Immunology. October 10, 2023. Accessed October 17, 2023. doi: 10.1016/j.jaci.2023.08.032.
