What is the efficacy and protocol for epicutaneous immunotherapy (EIT) using a peanut patch for treating peanut allergies?

Peanut Patch Study: Efficacy and Protocol

Primary Recommendation

The Viaskin Peanut 250 μg patch demonstrates modest but statistically significant efficacy for treating peanut allergy in children aged 6-11 years, with 50% achieving treatment response versus 25% with placebo after 12 months of daily application, though efficacy is limited in adolescents and adults. 1

Efficacy Data

Overall Treatment Response

• In the largest phase 2 trial (221 subjects, ages 6-55 years), the 250 μg patch achieved the primary endpoint with 50% treatment responders versus 25% placebo (P=0.01) at 12 months 1
• Treatment response was defined as achieving ≥10-times increase in eliciting dose from baseline and/or reaching ≥1000 mg of peanut protein 1
• Mean cumulative reactive dose at month 12 was 1117.8 mg for the 250 μg patch versus 469.3 mg for placebo 1

Age-Specific Efficacy (Critical Distinction)

• Children aged 6-11 years showed significant benefit: 53.6% response rate versus 19.4% placebo (difference 34.2%, P=0.008) 1
• Adolescents and adults (>11 years) showed NO significant difference: 46.4% versus 32.0% placebo (P=0.40) 1
• Age interaction was statistically significant only for the 250 μg dose (P=0.04) 1

Dose-Response Findings

• The 50 μg and 100 μg doses did NOT achieve statistical significance versus placebo 1
• Only the 250 μg daily dose demonstrated efficacy 1

Treatment Protocol

Patient Selection Criteria

• Patients must have documented peanut allergy with positive double-blind, placebo-controlled food challenge 2
• Baseline eliciting dose must be ≤300 mg of cumulative peanut protein 1, 2
• Age range studied: 4-55 years, though efficacy primarily demonstrated in 6-11 year age group 1, 2

Application Protocol

• Daily application of 250 μg peanut protein patch for 12 months minimum 1
• Patch should be applied for 12-16 hours daily to achieve sufficient allergen delivery 3
• Median application duration in clinical trials was 21.1 hours 3
• Subjects achieving >16 hours mean application duration (84.5% of treated population) had 38.8% response rate versus 13.4% placebo 3

Duration of Therapy

• Initial treatment period: 12 months to assess response 1
• Extended open-label treatment studied up to 3 years total (12 months controlled + 2 years open-label) 1

Safety Profile

Adverse Events

• Treatment-emergent adverse events occurred in 98.2-100% of active patch groups versus 92.9% placebo, but were predominantly mild local skin reactions at patch site 1
• Local skin reactions occurred with all VP250 doses but decreased in frequency over time 4
• Dropout rate for treatment-related adverse events was only 0.9% 2
• Overall adherence was 97.6% after 12 months 1

Serious Adverse Events

• No dose-related serious adverse events were observed 2
• Epinephrine was administered for allergic reactions in 2.4% of VP250-treated children, with none involving severe anaphylaxis 4
• 5 of 7 children requiring epinephrine remained in the study 4
• Only 1.4% of participants discontinued due to adverse events 4

Comparison to Oral Immunotherapy

• Peanut EPIT has significantly better safety profile than oral immunotherapy (OIT): OIT causes predominantly gastrointestinal symptoms in 66% versus 27% placebo, with 21% withdrawal rate 1
• EPIT adverse events are primarily local and mild, while OIT has rate of 35.9 events per year versus 12.1 for placebo 1

Predictive Factors for Response

Baseline Characteristics

• Higher baseline eliciting dose predicts better response at 12 months 5
• Lower baseline peanut-specific IgE predicts better response 5
• Younger age (6-11 years) strongly predicts better response 1, 5
• Baseline SCORAD score influences response 5

Patch Adhesion

• For 80% of subjects, patch detachment did not impact treatment response 5
• Even subjects with highest patch detachment rates demonstrated treatment benefit measured by fold-changes in geometric mean eliciting dose 5
• A minority of highly sensitive subjects had lower responder rates and higher patch detachment rates but still benefited from treatment 5

Immunologic Mechanisms

Observed Changes

• Increases in peanut-specific IgG4 levels and IgG4/IgE ratios in EPIT-treated participants 6
• Trends toward reduced basophil activation 6
• Reduction in peanut-specific TH2 cytokines 6

Critical Clinical Caveats

Current Regulatory Status

• As of 2018, peanut EPIT remained experimental without FDA or regulatory approval 1
• Phase 3 studies were ongoing with results expected 1
• The European Medicines Agency approved Palforzia (oral peanut immunotherapy) in December 2020, but this is a different modality than EPIT 1

Important Limitations

• Efficacy is modest: only 50% response rate in best-case scenario (children 6-11 years with 250 μg dose) 1
• No demonstrated efficacy in adolescents and adults 1
• Treatment does NOT eliminate peanut allergy; it increases threshold of reactivity 1
• Patients must continue strict peanut avoidance and carry epinephrine even during treatment 1, 7

Contraindications and Precautions

• Uncontrolled asthma is an absolute contraindication to food immunotherapy 1
• Patients with history of anaphylaxis require particularly careful monitoring 4
• All patients must maintain emergency preparedness with epinephrine autoinjectors 8, 7, 9

Practical Implementation Algorithm

Step 1: Patient Assessment

• Confirm peanut allergy with documented positive oral food challenge to ≤300 mg peanut protein 1, 2
• Measure baseline peanut-specific IgE (lower levels predict better response) 5
• Assess age: 6-11 years optimal, limited benefit if >11 years 1
• Evaluate baseline eliciting dose (higher baseline predicts better response) 5

Step 2: Treatment Initiation

• Apply 250 μg peanut protein patch daily 1
• Target 12-16 hours minimum daily application 3
• Monitor for local skin reactions (expected in nearly all patients) 4

Step 3: Ongoing Management

• Continue daily application for minimum 12 months before assessing response 1
• Maintain strict peanut avoidance throughout treatment 1, 7
• Ensure patient carries epinephrine autoinjectors at all times 8, 7, 9
• Monitor adherence (aim for >16 hours daily application) 3

Step 4: Response Assessment

• Perform oral food challenge at 12 months to measure change in eliciting dose 1
• Treatment success: ≥10-fold increase in eliciting dose or reaching ≥1000 mg peanut protein 1, 2
• Consider continuation for up to 3 years if demonstrating benefit 1