Safety Of Epicutaneous Immunotherapy Research Articles

From Skin to Solution: Exploring Epicutaneous Immunotherapy for Peanut Allergy-A Systematic Review and Meta-Analysis.

Peanut allergy is a leading cause of severe food reactions. This meta-analysis evaluates the efficacy and safety of epicutaneous immunotherapy (EPIT) compared to placebo for peanut-allergic individuals. After prospectively registering on PROSPERO, we searched three databases (PubMed, Google Scholar, and Cochrane CENTRAL) and 2 trial registries till September 2023. Analysis was conducted via RevMan where data was computed using risk ratios (RR). The Cochrane Risk of Bias tool and GRADE criteria were used to appraise and evaluate the evidence. From 4927 records, six multicenter randomized placebo-controlled trials comprising 1453 participants were included. The 250µg EPIT group had a significant increase in successful desensitization compared to placebo (RR: 2.13 (95% C.I: 1.72, 2.64), P < 0.01, I2 = 0%), while the 100µg EPIT group did not (RR: 1.54 (95% C.I: 0.92, 2.58), P = 0.10, I2 = 0%) (moderate certainty evidence). Moreover, there was a significant increase in local (RR: 1.69 (95% C.I: 1.06, 2.68), P = 0.03, I2 = 89%) and systemic adverse events (RR: 1.75 (95% C.I: 1.14, 2.69), P = 0.01, I2 = 0%) with EPIT. Additionally, individuals administered EPIT have an increased probability of requiring rescue medications like epinephrine (RR: 1.91 (95% C.I: 1.12, 3.28), P = 0.02, I2 = 0%) and topical corticosteroids (RR: 1.49 (95% C.I: 1.29, 1.73), P < 0.01, I2 = 0%) to treat adverse events. The association of adverse events post-treatment including anaphylaxis (RR: 2.31 (95% C.I: 1.00, 5.33), P = 0.05, I2 = 36%), skin/subcutaneous disorders like erythema or vesicles (RR: 0.93 (95% C.I: 0.79, 1.08), P = 0.33, I2 = 0%), and respiratory disorders like dyspnea or wheezing (RR: 0.94 (95% C.I: 0.77, 1.15), P = 0.55, I2 = 0%) with EPIT is inconclusive. EPIT, although effective in desensitization, is linked to an increased risk of adverse events. PROSPERO registration: CRD42023466600.

Varying Doses of Epicutaneous Immunotherapy With Viaskin Milk vs Placebo in Children With Cow’s Milk Allergy

No approved treatment exists for allergen-specific immunoglobulin E (IgE)-mediated cow's milk allergy (CMA), a common childhood food allergy. To assess dose, efficacy, and safety of epicutaneous immunotherapy with Viaskin milk in children with IgE-mediated CMA. A phase 1/2, 2-part, randomized, double-blind, placebo-controlled dose-ranging clinical trial in children aged 2 to 17 years with IgE-mediated CMA was conducted between November 2014 through December 2017. It took place at 17 trial sites in the US and Canada. Current CMA was confirmed by double-blind, placebo-controlled food challenge at study entry. Part A assessed the short-term safety of 150 μg, 300 μg, or 500 μg of Viaskin milk; part B evaluated the efficacy and safety of the 3 doses vs placebo over 12 months of treatment. Of the 308 screened participants with physician-diagnosed CMA, 198 met eligibility criteria (including an eliciting dose 300 mg or less) and were randomized. Safety of Viaskin milk (150-μg, 300-μg, or 500-μg doses) was evaluated over a 3-week period (part A). In part B, 180 additional participants were randomized to receive Viaskin milk at doses of 150 μg, 300 μg, or 500 μg or placebo (1:1:1:1) for 12 months. The primary outcome was the proportion of treatment responders, defined as a 10-fold or more increase in the cumulative reactive dose of cow's milk protein (reaching at least 144 mg) or a cumulative reactive dose of cow's milk protein at 1444 mg or more at the month 12 double-blind, placebo-controlled food challenge. A total of 95.5% of the randomized participants (mean [SD] age, 8 [4.17] years; 124 of 198 were male [62.6%]) completed treatment. The highest response rate was observed in participants who received Viaskin milk at the 300-μg dose with 24 of 49 responders (49.0%) overall vs 16 of 53 responders (30.2%) in the placebo group (odds ratio, 2.19; 95% CI, 0.91-5.41; P = .09), highest in the 2 to 11 years age group (22 of 38 [57.9%] vs 13 of 40 [32.5%]; P = .04). Most treatment-emergent adverse events were mild or moderate application-site reactions. One participant in the 500-μg Viaskin milk dose group experienced treatment-related anaphylaxis. In this randomized clinical trial, 12 months of daily epicutaneous immunotherapy with a dose of Viaskin milk at 300 μg was associated with a statistically significant treatment response in 2- to 11-year-old children with IgE-mediated CMA. Treatment-related anaphylaxis and treatment-related discontinuation rates were low. Further research is needed to explore Viaskin milk as a viable treatment option for children with IgE-mediated CMA. ClinicalTrials.gov Identifier: NCT02223182.

Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy

BackgroundNo approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown.MethodsWe conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo.ResultsOf the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group.ConclusionsIn this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247.)

Efficacy and Safety of Epicutaneous Immunotherapy (EPIT) for Peanut Allergy in Subjects Aged 1-3 Years With and Without Atopic Dermatitis in the EPITOPE Study

In a Phase 3 double-blind, placebo-controlled clinical trial of 1-3-year-old peanut-allergic children (EPITOPE), EPIT with Viaskin Peanut 250 μg patch (VP250) reduced reactivity to peanut ingestion. We explored whether treatment response or safety was influenced by baseline atopic dermatitis (AD) in this population.

Efficacy and Safety of Epicutaneous Immunotherapy (EPIT) for Peanut Allergy in Subjects Aged 1-3 Years With and Without Concomitant Food Allergies in the EPITOPE Study

Efficacy and Safety of Epicutaneous Immunotherapy (EPIT) for Peanut Allergy in Subjects Aged 1-3 Years With and Without Concomitant Food Allergies in the EPITOPE Study

EPITOPE STUDY RESULTS: PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF EPICUTANEOUS IMMUNOTHERAPY IN PEANUT-ALLERGIC TODDLERS

<h3>Introduction</h3> No approved peanut allergy treatments exist for children <4 years old. This study aimed to assess the efficacy and safety of epicutaneous immunotherapy with a patch containing 250 µg peanut protein among peanut-allergic children ages 1-3 years. <h3>Methods</h3> In a Phase 3, multicenter, randomized, double-blind, placebo-controlled trial (EPITOPE), peanut-allergic children developing symptoms meeting stopping criteria during double-blind, placebo-controlled food challenge (DBPCFC) at an eliciting dose (ED) ≤300 mg peanut protein were randomized 2:1 to 12 months of daily treatment with the peanut patch (n=244) or placebo patch (n=118). The primary outcome was the percent difference in responders between active and placebo, determined by DBPCFC ED at baseline and Month 12. Safety was assessed by treatment-emergent adverse event (TEAE) rate. <h3>Results</h3> Of 362 participants randomized (median age: 2.5 years, 68.8% male), 84.8% completed treatment. The primary efficacy endpoint was met by 67% receiving active peanut patch vs. 33.5% receiving placebo (difference=33.4%; 95% CI: 22.4–44.5% [p<i><</i>0.001]). Additionally, 64.2% active vs. 29.6% placebo recipients (difference=34.7%; [p<i><</i>0.001]) achieved a peanut protein ED ≥1000 mg. The majority of TEAEs were mild or moderate application site reactions. Serious TEAEs occurred in 8.6% peanut patch vs. 2.5% placebo recipients, with 1.6% (n=4) peanut patch subjects experiencing treatment-related anaphylaxis, and 3.3% (n=8) peanut patch subjects discontinuing due to a TEAE. <h3>Conclusions</h3> Twelve months of epicutaneous immunotherapy with a patch containing 250 µg peanut protein was associated with a statistically significant response vs. placebo among peanut-allergic children aged 1-3 years. Rates of treatment-related anaphylaxis and discontinuations due to TEAEs were low.

Safety of Epicutaneous Immunotherapy in Peanut-Allergic Children: REALISE Randomized Clinical Trial Results

Treatment options for peanut allergy are limited. In previous clinical trials, epicutaneous immunotherapy with a patch containing 250-μg peanut protein (Viaskin Peanut 250 μg [VP250]) was well tolerated and statistically superior to placebo in desensitizing peanut-allergic children. To examine the safety of VP250 in children, using a study design approximating potential real-world use. REAL LIfe Use and Safety of EPIT (REALISE) is a phase 3 multicenter study consisting of a 6-month, randomized, double-blind, placebo-controlled period followed by open-label active treatment. Children aged 4 to 11 years with physician diagnosis of peanut allergy received daily treatment with placebo (6 months) or VP250 (up to 36 months). Data from the 6-month, randomized, controlled phase of REALISE are reported. Three hundred ninety-three children were randomized 3:1 to receive VP250 (n= 294) or placebo (n= 99) for 6 months; 284 (72.3%) children had a history of peanut anaphylaxis. According to parent diary, all participants receiving VP250 and 83.8% receiving placebo reported at least 1 episode of local skin reaction, with frequency decreasing over time. Only 4 participants (1.4%) receiving VP250 discontinued because of adverse events (AEs). Epinephrine was administered for allergic reactions attributed to VP250 in 7 children (2.4%), of whom 5 remained in the study; none involved severe anaphylaxis. Overall, AE rates were similar among participants with and without a history of peanut anaphylaxis. In a study designed to mirror real-world use, VP250 was observed to be well tolerated in peanut-allergic children, consistent with previous phase 2b and 3 studies.

M110 SIGNIFICANTLY INCREASED THRESHOLD DOSE AFTER LONG-TERM PEANUT EPICUTANEOUS IMMUNOTHERAPY AND DAILY ORAL PEANUT INTAKE

While research has demonstrated the efficacy and safety of epicutaneous immunotherapy (EPIT) for peanut allergy, questions still exist regarding its ability to induce sustained unresponsiveness (SU) and maintained desensitization once achieved. We describe a patient with significantly increased threshold dose to peanut following EPIT despite inconsistent oral ingestion – evidence of a real-world situation.

PEANUT ALLERGEN IMMUNOTHERAPY: ONLINE EDUCATION IMPROVES KNOWLEDGE OF ALLERGIST LEARNERS

Introduction A study was conducted to determine if an online educational intervention could improve knowledge and competence of allergists in the latest research on peanut allergen immunotherapies. Methods A 30-minute online educational intervention consisting of 3 video-based expert discussions among two faculty each covered topics related to the latest research on peanut allergen immunotherapy. Educational effect was evaluated with a repeated-pairs pre- to post-assessment study design in which each individual learner acts as his/her own control. A paired 2-tailed t-test evaluated whether the mean pre- and post-assessment scores significantly differed from one another and Pearson's X2 test measured changes in paired responses to individual questions. Cramer's V was used to calculate the effect size of the intervention. Data from the educational intervention were collected between September 28, 2017 and November 14, 2017. Results Participation in education resulted in statistically significant improvements and an extensive educational effect for allergists (n=155; P • Identification of the role of epidermal Langerhans cells in activating regulatory T cells (28% improvement) • Knowledge of safety of epicutaneous immunotherapy for peanut allergy (9% improvement) • Importance of the clinical relevance of a higher peanut protein threshold (105% improvement) • Confidence in discussing evidence regarding peanut allergen immunotherapy with patients (62% improvement) Conclusions Participation in online, video-based expert discussions of latest research in peanut allergen immunotherapies resulted in significant improvement in knowledge of allergists.