Epicutaneous immunotherapy with Viaskin™ Peanut in toddlers: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of an article published in The New England Journal of Medicine about the EPITOPE clinical study, which tested a skin patch called ViaskinTM Peanut 250 µg (micrograms) as a treatment option for peanut allergy in children aged 1 through 3 years. The patch is a form of epicutaneous immunotherapy (EPIT), which is a new approach to allergen immunotherapy that delivers a small amount of peanut protein to the immune system through the skin. Viaskin Peanut is an investigational therapy, meaning it has not yet been approved by the United States Food and Drug Administration (FDA), that has been studied before in young children aged 4 through 11 years. In those studies, the children who received the patch were desensitized and were less likely to experience anaphylaxis when they ate peanut at the end of the study. The EPITOPE study included children aged 1 through 3 years with peanut allergy and looked at how well the peanut patch worked and how safe it was compared to a patch with no medicine (placebo, no medicine) after 12 months. WHAT WERE THE KEY TAKEAWAYS?: The study showed that the peanut patch was better in desensitizing children to peanuts than the placebo patch. Most of the children in the study who received the peanut patch for 12 months (the treatment group) were able to eat and tolerate more peanut at the end of the study than those who received only the placebo patch (the control group). This demonstrates that the children in the treatment group were less likely to have an allergic reaction if they ate peanut by accident at the end of the study. The children in the treatment group also had less severe symptoms when they were given peanut during the oral food challenges at the end of the study. Most children in both groups experienced side effects. Mild to moderate local skin reactions where the patch was applied were most common. These side effects happened less often and were less serious over the 12-month treatment period. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?: Overall, these results show the peanut patch may be a possible treatment option to help desensitize young children with peanut allergy to peanut.

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

BACKGROUND: 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. OBJECTIVE: To examine the safety of VP250 in children, using a study design approximating potential real-world use. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Towards an FDA-cleared basophil activation test.

Food allergy is a global health problem affecting up to 10% of the world population. Accurate diagnosis of food allergies, however, is still a major challenge in medical offices and for patients seeking alternative avenues of diagnosis. A flawless test to confirm or rule out a food allergy does not exist. The lack of optimum testing methods to establish precise clinical correlations remains a major obstacle to effective treatment. Certain IgE measurement methods, including component testing, have received FDA clearance, but they have been used primarily as an analytical tool and not to establish clinical correlations. Most allergy tests are still carried out within the laboratory, and skin tests outside a laboratory setting that are used for food allergy diagnosis rely on non-standardized allergens, according to the FDA definition. Epitope mapping and basophil activation test (BAT) have recently been proposed as a means of establishing better clinical correlations. Yet neither have received FDA clearance for widespread distribution. Of the two methods, the BAT has the advantage of being a functional assay. Over the past few years, several large private practice groups in the United States, have developed BAT as a clinical assay and have started using it in patient care. Given this clinical experience, the vast number of papers published on BAT (more than 1,400 as of 2022) and the trend toward increasing FDA regulation, it is essential to understand the roadmap for regulatory clearance of this assay.

Continuous and Daily Oral Immunotherapy for Peanut Allergy: Results from a 2-Year Open-Label Follow-On Study.

BACKGROUND: The randomized, controlled PALISADE trial demonstrated the benefit of daily oral immunotherapy with Peanut (Arachis Hypogaea) allergen powder-dnfp (PTAH, formerly AR101) in peanut-allergic children and adolescents. OBJECTIVE: ARC004, the open-label follow-on study to PALISADE, used 5 dosing cohorts to explore PTAH treatment beyond 1 year and alternative dosing regimens in peanut-allergic individuals. METHODS: Active arm (PTAH-continuing) PALISADE participants who tolerated 300-mg peanut protein at the exit double-blind placebo-controlled food challenge and placebo arm (PTAH-naive) participants could enter ARC004. PTAH-continuing participants were assigned to receive daily (cohorts 1 and 3A) or non-daily (cohorts 2, 3B, and 3C) dosing regimens; PTAH-naive participants were built up to 300 mg/d PTAH, followed by maintenance dosing. At study completion, participants underwent an exit double-blind placebo-controlled food challenge with doses up to 2000 mg peanut protein. Data were assessed using descriptive statistics. RESULTS: Overall, 358 (87.5%) eligible participants (4-17 years) entered ARC004 (PTAH-continuing, n = 256; PTAH-naive, n = 102). Among PTAH-continuing participants, exposure-adjusted adverse event rates were 12.94 to 17.54/participant-year and 25.95 to 42.49/participant-year in daily and non-daily dosing cohorts, respectively; most participants (83%) experienced mild or moderate adverse events. Daily dosing cohorts appeared to have higher desensitization rates than non-daily dosing cohorts. Of all PTAH-continuing cohorts, cohort 3A had the longest daily dosing duration and the highest desensitization rates. Changes in immune markers with PTAH continuation demonstrated ongoing immunomodulation. Outcomes in PTAH-naive participants mirrored those of the PALISADE active arm. CONCLUSIONS: Continued daily PTAH treatment beyond 1 year showed sustained safety and efficacy. Ongoing immunomodulation was observed during the second year of treatment.

Distinguishing alpha1-antitrypsin deficiency from asthma.

OBJECTIVE: To explore the relations that exist between α1-antitrypsin deficiency (AATD) and asthma and to evaluate practices for screening patients with asthma for this genetically determined condition in the context of current guidelines. DATA SOURCES: English-language articles were selected from a PubMed search using combinations of the following search terms: alpha1-antitrypsin, screening, and asthma. STUDY SELECTIONS: Studies to be included in this review were based on the authors' expert opinions. RESULTS: Asthma and AATD are 2 distinct conditions yet they can coexist. Although AATD has a variable symptomatology and some patients may be asymptomatic, many can present with symptoms that are similar to those of asthma, such as dyspnea, wheezing, cough, and mucus production, which can cause confusion at diagnosis. A simple genetic test exists for AATD, which is a single-gene disorder, and the American Thoracic Society and European Respiratory Society guidelines recommend the screening of patients with asthma who exhibit chronic airflow obstruction. Patients with AATD are seen by internal medicine, family medicine, allergy, and pulmonary clinicians, yet there is a generalized lack of awareness of testing among all specialties. This leads to a delayed diagnosis for patients with AATD, typically by 8.3 years. CONCLUSION: A greater awareness of AATD among clinicians who regularly manage patients with asthma symptoms could increase diagnosis rates, thus optimizing interventions and management strategies to improve patient outcomes.

Induction of tolerance to warfarin after anaphylaxis with a desensitization protocol.

Warfarin hypersensitivity is exceedingly rare. A 59-year-old male with acute renal infarction and a history of allergy to warfarin underwent evaluation, confirming presence of warfarin hypersensitivity. Induction of tolerance to warfarin was successfully completed using an oral desensitization protocol, which has not previously been reported.

Egg allergy and influenza vaccination.

Many egg-allergic patients are unnecessarily restricted from receiving the influenza vaccine. Patients with suspected egg allergy who require seasonal or H1N1 influenza vaccination can pose a significant challenge and should be appropriately evaluated by an allergist/immunologist. In most cases, if the benefits are felt to outweigh the risks, precautionary measures are available that can enhance safe vaccine administration. A case of influenza vaccine management in a child with egg allergy is presented. Clinical characteristics, diagnostic testing, case management, and natural history are reviewed. Clinical Pearls and Pitfalls include: (1) Batch-to-batch variability of egg content in extant influenza vaccines necessitates an informed and cautious approach to vaccination of an egg-allergic individual. (2) Due to denaturation of some egg proteins through heating, tolerance of "baked egg" products may not predict tolerance of "native egg" proteins present in the influenza vaccine. (3) Intradermal skin testing with influenza vaccine diluted 1:10 may be irritating to the skin and result in false positive results. (4) If skin test to the vaccine is positive, vaccination may still be cautiously administered, if necessary, in a graded-dose protocol, as presented herein. (5) Most patients with egg allergy are likely to develop egg tolerance by late childhood.