A systematic review and expert Delphi Consensus recommendation on the use of vaccines in patients receiving dupilumab: A position paper of the American College of Allergy, Asthma and Immunology.

BACKGROUND: Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians. OBJECTIVE: To perform a systematic review of literature on the safety and efficacy of vaccinations in patients who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab. METHODS: A systematic review of the literature was performed, and an expert Delphi Panel was assembled. RESULTS: The available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective. CONCLUSION: Vaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity.

Food allergies on a college campus.

There are limited data on food allergies among college students. In this article, we review the most current available studies. These self-reported surveys and qualitative interviews reported overall poor avoidance of known allergens and low rates of carrying self-injectable epinephrine among students with food allergy. College students may exhibit risk-taking food behaviors due to a number of factors, including age-appropriate risk-taking predilection, strong social influences, and lack of experience in self-advocacy. Having to disclose an otherwise invisible condition repeatedly in a new environment may also lead to "disclosure fatigue," creating an additional barrier to self-advocacy. Common themes in the narrative include hypervigilance, stigma management, and concern about others' misunderstanding of food allergy. Although there is a paucity of data in this area, it is likely that having greater support at the institution level, along with support from peers and faculty, may help improve awareness, self-injectable epinephrine carriage, and allergen avoidance. This review also discusses strategies for preparedness at school, including specific steps to maximize safety.

COVID-19 and Pregnancy: Interrelationships With Asthma and Allergy.

Pregnant individuals are at higher risk of complications from respiratory viruses such as coronavirus-19 disease (COVID-19). Altered lung function, vaccine hesitancy, and resistance to taking necessary medications because of a lack of safety data in pregnancy make this population especially vulnerable to the effects of COVID-19. Like many medical conditions, the treatment of allergic conditions, including asthma and allergic rhinitis, were affected during the pandemic, with decreased numbers of in-person visits and interruptions in medical treatment. There were initially no data to allow pregnant women with asthma know whether the condition put them at higher risk of complications from COVID-19. There are now increasing data for the efficacy and safety of vaccines for COVID-19 in at-risk populations, including pregnant women. Vaccine studies show no increased risk for spontaneous abortion, congenital anomalies, or pregnancy complications. Furthermore, infants of individuals vaccinated during pregnancy have been shown to obtain protective antibodies via the placenta, providing protection against COVID-19 after birth. Although overall risks are low, pregnant women who become infected with COVID-19 are at higher risk for maternal and pregnancy complications. Antiviral treatment is available for pregnant women with mild to moderate symptoms of COVID-19, with reassuring safety data to date. Dexamethasone is the mainstay of inpatient therapy.

COVID-19 Treatments: Then and Now.

The coronavirus disease 2019 (COVID-19) pandemic has evolved over the past 3+ years, and strategies to prevent illness and treat infection have changed over time. As COVID-19 transitions from a pandemic to an endemic infection, widespread nonpharmaceutical interventions such as mask mandates and governmental policies requiring social distancing have given way to more selective strategies for risk mitigation. Monoclonal antibody therapies used for disease prevention and treatment lost utility owing to the emergence of resistant viral variants. Oral antiviral medications have become the mainstay of treatment in nonhospitalized individuals, whereas systemic corticosteroids remain the cornerstone of therapy in those requiring supplemental oxygen. Emerging literature also supports the use of additional immune-modulating therapies in select admitted patients. Importantly, the COVID-19 pandemic highlighted both unprecedented research and development of medical interventions while also drawing attention to significant pitfalls in the global response. This review provides a comprehensive update in prevention and management of COVID-19.

Outcomes of oral food challenges in a real-world setting, with predictors of outcomes.

BACKGROUND: Oral food challenge (OFC) remains the reference standard for food allergy (FA) diagnosis. OBJECTIVE: This study reports a single-center observational experience with all OFCs conducted over 3 years. METHODS: All OFCs performed at an outpatient office were tracked. The OFCs were conducted without strict prespecified inclusion or exclusion criteria. Demographic information along with results of diagnostic testing and results of the OFCs were recorded. RESULTS: A total of 1132 OFCs were performed, with a median age of 4 years (interquartile range = 2.0-10.0). Of the 1132 OFCs, 862 (76.1%) tolerated the food, whereas 232 (20.5%) experienced a reaction, and 38 (3.4%) did not complete the OFC because of food refusal. The highest percentage of tolerated food was shellfish (91.1%), with the lowest percentage of tolerated food being baked egg (66.1%). There were 66 (5.8%) OFCs that were deemed to be high risk, of which 35 (53.0%) tolerated the food. More than 50% of reactions occurred on the first or second dose, with the most common clinical symptom being urticaria or angioedema, with 29.2% of reactions treated with epinephrine. There were several factors that predicted tolerating an OFC, including the food challenge, the reason for food avoidance, older age at the time of OFC and less reactive skin prick testing, and lower food-specific immunoglobulin E levels. CONCLUSION: Certain factors can predict tolerating an OFC, and even those considered to be high risk can be safely completed in an outpatient setting, with most tolerating the food, and most reactions not requiring treatment with epinephrine.

Recommendations for Management of Secondary Antibody Deficiency in Multiple Myeloma.

Secondary antibody deficiency (SAD) is a subtype of secondary immunodeficiency characterized by low serum antibody concentrations (hypogammaglobulinemia) or poor antibody function. SAD is common in patients with multiple myeloma (MM) due to underlying disease pathophysiology and treatment-related immune system effects. Patients with SAD are more susceptible to infections and infection-related morbidity and mortality. With therapeutic advancements improving MM disease control and survival, it is increasingly important to recognize and treat the often-overlooked concurrent immunodeficiency present in patients with MM. The aims of this review are to define SAD and its consequences in MM, increase SAD awareness, and provide recommendations for SAD management. Based on expert panel discussions at a standalone meeting and supportive literature, several recommendations were made. Firstly, all patients with MM should be suspected to have SAD regardless of serum antibody concentrations. Patients should be evaluated for immunodeficiency at MM diagnosis and stratified into management categories based on their individualized risk of SAD and infection. Infection-prevention strategy education, early infection reporting, and anti-infective prophylaxis are key. We recommend prophylactic antibiotics or immunoglobulin replacement therapy (IgRT) should be considered in patients with severe hypogammaglobulinemia associated with a recurrent or persistent infection. To ensure an individualized and efficient treatment approach is utilized, patient's immunoglobin G concentration and infection burden should be closely monitored throughout treatment. Patient choice regarding route and IgRT treatment is also key in reducing treatment burden. Together, these recommendations and proposed management algorithms can be used to aid physician decision-making to improve patient outcomes.

Immune response evolution in peanut epicutaneous immunotherapy for peanut-allergic children.

BACKGROUND: Epicutaneous immunotherapy with investigational Viaskin™ Peanut 250 µg (DBV712) has demonstrated statistically superior desensitization versus placebo in peanut-allergic children in clinical trials. It is unclear whether serologic biomarkers predict response. METHODS: Serum-specific IgG4 and IgE (whole peanut and components) from subjects enrolled in the phase 3 Efficacy and Safety of Viaskin Peanut in Children With IgE-Mediated Peanut Allergy study were examined by exploratory univariate and multivariate analyses to determine trajectories and predictors of treatment response, based upon peanut protein eliciting dose (ED) at Month (M) 12 double-blind placebo-controlled food challenge. RESULTS: Among Viaskin Peanut-treated subjects, peanut sIgG4 significantly increased from baseline through M12 and peanut sIgE peaked at M3 and fell below baseline by M12, with sIgG4 and sIgE peanut components mirroring these trajectories. Placebo subjects had no significant changes. By univariate analysis, M12 peanut sIgG4/sIgE was higher in treatment responders (p < 0.001) and had highest area under the curve (AUC) for predicting ED ≥300 mg and ≥1000 mg (AUC 69.5% and 69.9%, respectively). M12 peanut sIgG4/sIgE >20.1 predicted M12 ED ≥300 mg (80% positive predictive value). The best performing component was Ara h 1 sIgE <15.7 kUA /L (AUC 66.5%). A multivariate model combining Ara h 1 and peanut sIgG4/sIgE had an AUC of 68.2% (ED ≥300 mg) and 67.8% (ED ≥1000 mg). CONCLUSIONS: Peanut sIgG4 rise most clearly differentiated Viaskin Peanut versus placebo subjects. sIgG4/sIgE ratios >20.1 and the combination of Ara h 1 and peanut sIgG4/sIgE had moderate ability to predict treatment response and could potentially be useful for clinical monitoring. Additional data are needed to confirm these relationships.

Agents contributing to secondary immunodeficiency development in patients with multiple myeloma, chronic lymphocytic leukemia and non-Hodgkin lymphoma: A systematic literature review.

Introduction: Patients with hematological malignancies (HMs), like chronic lymphocytic leukemia (CLL), multiple myeloma (MM), and non-Hodgkin lymphoma (NHL), have a high risk of secondary immunodeficiency (SID), SID-related infections, and mortality. Here, we report the results of a systematic literature review on the potential association of various cancer regimens with infection rates, neutropenia, lymphocytopenia, or hypogammaglobulinemia, indicative of SID. Methods: A systematic literature search was performed in 03/2022 using PubMed to search for clinical trials that mentioned in the title and/or abstract selected cancer (CLL, MM, or NHL) treatments covering 12 classes of drugs, including B-lineage monoclonal antibodies, CAR T therapies, proteasome inhibitors, kinase inhibitors, immunomodulators, antimetabolites, anti-tumor antibiotics, alkylating agents, Bcl-2 antagonists, histone deacetylase inhibitors, vinca alkaloids, and selective inhibitors of nuclear export. To be included, a publication had to report at least one of the following: percentages of patients with any grade and/or grade ≥3 infections, any grade and/or grade ≥3 neutropenia, or hypogammaglobulinemia. From the relevant publications, the percentages of patients with lymphocytopenia and specific types of infection (fungal, viral, bacterial, respiratory [upper or lower respiratory tract], bronchitis, pneumonia, urinary tract infection, skin, gastrointestinal, and sepsis) were collected. Results: Of 89 relevant studies, 17, 38, and 34 included patients with CLL, MM, and NHL, respectively. In CLL, MM, and NHL, any grade infections were seen in 51.3%, 35.9% and 31.1% of patients, and any grade neutropenia in 36.3%, 36.4%, and 35.4% of patients, respectively. The highest proportion of patients with grade ≥3 infections across classes of drugs were: 41.0% in patients with MM treated with a B-lineage monoclonal antibody combination; and 29.9% and 38.0% of patients with CLL and NHL treated with a kinase inhibitor combination, respectively. In the limited studies, the mean percentage of patients with lymphocytopenia was 1.9%, 11.9%, and 38.6% in CLL, MM, and NHL, respectively. Two studies reported the proportion of patients with hypogammaglobulinemia: 0-15.3% in CLL and 5.9% in NHL (no studies reported hypogammaglobulinemia in MM). Conclusion: This review highlights cancer treatments contributing to infections and neutropenia, potentially related to SID, and shows underreporting of hypogammaglobulinemia and lymphocytopenia before and during HM therapies.

Steroid-induced secondary immune deficiency.

Despite their widespread clinical use, oral corticosteroids (OCSs) are well known to be associated with a myriad of adverse effects, including immunosuppression. By inhibiting transcription factors and affecting leukocyte function, prolonged OCS use leads to significant CD4 lymphopenia and often a decrease in serum immunoglobulin (Ig)G. Conversely, OCS use has minimal impact on circulating B cell, serum IgM, or serum IgA levels. Although there is a paucity of literature, individuals treated with prolonged OCS seem to typically maintain humoral response to various vaccinations despite hypogammaglobinemia, but this area warrants additional research, especially in the setting of the coronavirus disease 2019 pandemic. Individuals treated with prolonged OCS use are most at risk for opportunistic infections, especially those with underlying malignancy and history of bone marrow transplant. Risk mitigation strategies to decrease infectious complication with OCS use include limiting the dose and duration of therapy, appropriately completing a full vaccination series, consideration for passive immunization, and prophylaxis against opportunistic infections.

Real-World Experience of Tixagevimab and Cilgavimab (Evusheld) in Rheumatologic Patients on Rituximab.

BACKGROUND/OBJECTIVE: Although vaccination is the primary strategy against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), rheumatologic patients on B-cell depleting agent rituximab may have a suboptimal response. Tixagevimab and cilgavimab (Evusheld) could be administered under Food and Drug Administration emergency use authorization as pre-exposure prophylaxis. METHODS: A cohort study of rheumatologic patients on rituximab therapy who received Evusheld was followed longitudinally. Adverse events were monitored. RESULTS: Forty-three patients received Evusheld, with diagnoses including rheumatoid arthritis, ANCA vasculitis, immune-mediated myositis, Sjögren disease, and systemic lupus erythematosus. Average time to follow-up was 100 ± 33 days. One patient experienced symptomatic infection with SARS-CoV-2 confirmed by home antigen test twice. A total of 97.8% of patients during follow-up did not contract acute SARS-CoV-2 infection. At the same time, 32,074 new local cases were reported with a local cumulative SARS-CoV-2 incidence rate of 4.32%. Adverse events included myalgia, flu-like symptoms, fevers, injection site pain, or headache. No serious adverse events, anaphylaxis, or cardiac events occurred. CONCLUSIONS: Evusheld demonstrated effectiveness in preventing symptomatic SARS-CoV-2 infection in a real-world cohort of rheumatologic patients on rituximab therapy. Administration of Evusheld may be considered as part of a multilayered approach to risk mitigation in this high-risk population as pre-exposure prophylaxis.

Management of secondary immunodeficiency in hematological malignancies in the era of modern oncology.

Secondary immunodeficiency (SID) in patients with B-cell hematological malignancies is a common condition that presents with recurrent infection. SID is due to both the inherent immune defects due to the malignancy, as well as secondary to cancer therapies, many of which have B-cell depleting properties. The early diagnosis of SID and the optimization of intervention strategies are key to delivering the most effective cancer treatments and reducing infection-related morbidity and mortality. This review discusses current practice, recommendations, and challenges for SID diagnosis, based on the evaluation of clinical history and laboratory assessments, and the effectiveness of specific vaccines and immunoglobulin replacement therapy in reducing the frequency and recurrence of infections in patients with SID, and the healthcare system-associated costs.