The Role of Eosinophils in Immunotherapy.

PURPOSE OF REVIEW: The purpose of this review is to provide a brief discussion on the differential diagnosis for peripheral eosinophilia. We will then focus on targeted immunotherapies for atopic disease, their effects on absolute peripheral eosinophil counts, and use of peripheral eosinophils as a predictor of treatment response. RECENT FINDINGS: In atopic disease, lower absolute peripheral eosinophil counts are typically associated with improved outcomes. Much of the current evidence on eosinophils as a biomarker comes from post hoc analyses in therapeutic immunotherapy. While changes in eosinophilia were not the primary outcome of interest in many studies, some patterns did emerge. Cytolytic monoclonal antibodies AK002 and benralizumab completely reduce peripheral and tissue eosinophil numbers. Dupilumab may have paradoxical transient eosinophilia despite observed clinical efficacy. Atopic inflammation is complex largely due to the various cytokines which affect eosinophil activation, proliferation, differentiation, and survival. This demonstrates the challenges of using peripheral eosinophilia alone as a biomarker for atopic disease activity. More attention should spotlight how different immunotherapy modalities affect eosinophil-driven responses.

The cost-effectiveness of requiring universal vs contextual self-injectable epinephrine autoinjector for allergen immunotherapy.

BACKGROUND: Aeroallergen immunotherapy (AIT) is a safe and effective disease-modifying treatment associated with rare therapy-associated fatality. Significant practice variation surrounds universal or contextual prescription of self-injectable epinephrine (SIE) for patients receiving AIT. OBJECTIVE: To characterize the cost-effectiveness of a universal vs contextual SIE requirement for patients receiving AIT. METHODS: An economic evaluation using cohort and microsimulation was performed from both the societal and health care sector perspectives for patients undergoing AIT, assessing a universal requirement to fill SIE prescriptions at the outset of therapy compared with requiring this only after a systemic reaction to immunotherapy (SRIT). RESULTS: A universal SIE requirement for AIT is not cost-effective, with the incremental cost-effectiveness ratio for this strategy estimated at $669,327,730 per quality-adjusted life-year (QALY). In the microsimulation (n = 10,000), the mean (SD) costs of a universal approach exceeded that of a more context-specific strategy where SIE was only prescribed for patients after an initial SRIT ($19,653.36 [$4296.66] vs $16,232.14 [$5204.32]), and given the effects on rates of AIT discontinuation, the universal approach was less effective (mean [SD], 25.555 [2.285] QALYs) compared with a contextualized approach (mean [SD], 25.579 [2.345] QALYs). Universal SIE prescription could be cost-effective if it provided a 1000 times protection against AIT fatality at a value-based cost of $24, and the annual AIT fatality rates unrealistically exceed 2.6 per 10,000 patients. CONCLUSION: In a simulation of potential SIE-prescribing strategies for patients receiving AIT, a universal approach to an epinephrine autoinjector requirement was not cost-effective when compared with an approach in which an SIE is prescribed only to patients with prior SRIT.

A Benefit-Risk Conceptual Framework for Biologic Use During Pregnancy: A Mini-Review.

Recent reports related to in utero exposure of marketed immunosuppressive biologics led to clinical recommendations to delay live vaccinations for infants due to the concern of reduced vaccine effectiveness and/or increased risk of vaccine-related disease. These delays can increase the risk of children contracting vaccine preventable diseases, yet the alternative cessation of biologics during pregnancy may result in increased autoimmune disease activity for the pregnant person, raising complex benefit-risk (B-R) considerations and trade-offs. Our goal is to develop a conceptual framework for B-R assessment based on the key benefits and risks pregnant people would consider for themselves and their children when continuing (vs. discontinuing) a biologic during pregnancy. The proposed framework defines the decision contexts, key domains and attributes for potential benefits, and risks of biologic use during pregnancy, informed by a literature review of indications for biologics and refined with key clinical stakeholders. The framework includes both the pregnant person taking the biologic and the infant potentially exposed to the biologic in utero, with potential benefit and risk domains and attributes for each participant. To advance this conceptual framework, there are considerations of potential biases and uncertainty of available data that will be imperative to address when quantifying the B-R framework. For these reasons, we recommend the formation of a consortium to ensure development of a robust, validated framework that can be adopted in the healthcare setting.

Increasing Cefazolin Use for Perioperative Antibiotic Prophylaxis in Penicillin-Allergic Children.

BACKGROUND AND OBJECTIVES: Cefazolin, a first-generation cephalosporin, is the most commonly recommended antibiotic for perioperative prophylaxis to reduce surgical site infections. Children with a reported penicillin allergy often receive an alternative antibiotic because of a common misunderstanding of the cross-reactivity between these antibiotics. This use of alternative antibiotics in surgical populations have been associated with increased infections, antibiotic resistance, and health care costs. We aimed to increase the percentage of patients with nonsevere penicillin-class allergies who receive cefazolin for antibiotic prophylaxis. METHODS: A multidisciplinary team conducted this quality improvement initiative, with a series of 3 plan-do-study-act cycles aimed at children with nonsevere penicillin-class allergies undergoing surgical procedures that require antibiotic prophylaxis. The primary outcome measure was the percentage of surgical encounters among patients with nonsevere penicillin-class allergies who received cefazolin as antibiotic prophylaxis. Statistical process control charts were used to measure improvement over time. RESULTS: Approximately 400 children were involved in this project. There was special cause variation and a shift in the center line from 60% to 80% of eligible patients receiving cefazolin for antibiotic prophylaxis, which was sustained for the duration of the project. In the last month, 90% of eligible patient received cefazolin, surpassing our goal of 85%. This improvement has been sustained in the 5 months after project completion. We had no cases of severe allergic reactions in the operating room. CONCLUSIONS: Our multidisciplinary education-focused interventions were associated with a significant increase in the use of cefazolin for perioperative antibiotic prophylaxis in patient with penicillin allergies.

Eosinophilic esophagitis during sublingual and oral allergen immunotherapy.

PURPOSE OF REVIEW: The aim of this review is to discuss the current evidence regarding the development of eosinophilic esophagitis (EoE) in individuals undergoing oral and sublingual immunotherapy (SLIT) for both food and environmental allergens. Cumulative incidence of EoE in patients on allergen immunotherapy for peanut, milk, and egg is estimated. RECENT FINDINGS: De novo development of EoE in patients undergoing oral and SLIT has been demonstrated on the scale of case reports and prospective randomized trials. However, few individuals with EoE-like symptoms during immunotherapy undergo endoscopy, and the long-term outcomes of immunotherapy-associated EoE are unknown. SUMMARY: Evidence exists to suggest that allergen immunotherapy could place individuals at risk for the development of EoE, the true incidence of which may vary depending on antigen exposure and methods used to define the condition.