Trends in anaphylaxis management during COVID-19.

Background: Anaphylaxis is an acute, potentially life-threatening systemic hypersensitivity reaction that commonly occurs in the community setting and is best managed with epinephrine. Objective: The purpose of this study was to examine the effects of the coronavirus 2019 disease (COVID-19) pandemic on trends in acute at-home anaphylactic events, including emergency room (ER) visits and treatment for anaphylaxis. Methods: We used data from 2 sources: survey data from the Food Allergy Research and Education Patient Registry and the electronic medical records of patients who presented to the Tampa General Hospital ER with a diagnosis of anaphylaxis. We collected data from events during the COVID-19 epidemic as well as before and after availability of the COVID-19 vaccine. The data were analyzed using descriptive statistics. Results: A total of 190 Food Allergy Research and Education survey responses were completed. Of the 190 respondents, 63 reported that the COVID-19 pandemic changed how they responded to an allergic reaction. Of the 63 patients, 71% avoided seeking medical care outside the home, 30% used self-medication more quickly than usual, and 14% delayed their use of medication. Only 87 events (46%) were treated with epinephrine. From April 1, 2018, to March 31, 2022, a total of 4358 individuals presented to the Tampa General Hospital ER with an International Classification of Diseases, 10th Revision, diagnosis code of anaphylaxis or allergic reaction. Only 718 individuals received epinephrine in the ER. In all, 867 patients presented 1 year before March 1, 2020 (before availability of the COVID-19 vaccine), and 1833 patients presented 1 year after April 1, 2021 (after availability of the vaccine). Conclusions: According to the survey and ER data capture, only 16% of patients received epinephrine. After COVID-19 vaccine availability there were more ER visits for anaphylaxis among patients seen in a tertiary care teaching hospital.

Development of neffy, an Epinephrine Nasal Spray, for Severe Allergic Reactions.

Epinephrine autoinjectors (EAIs) are used for the treatment of severe allergic reactions in a community setting; however, their utility is limited by low prescription fulfillment rates, failure to carry, and failure to use due to fear of needles. Given that delayed administration of epinephrine is associated with increased morbidity/mortality, there has been a growing interest in developing needle-free, easy-to-use delivery devices. neffy (epinephrine nasal spray) consists of three Food and Drug Administration (FDA)-approved components: epinephrine, Intravail A3 (absorption enhancer), and a Unit Dose Spray (UDS). neffy's development pathway was established in conjunction with the FDA and the European Medicines Agency and included multiple clinical trials to evaluate pharmacokinetic and pharmacodynamic responses under a variety of conditions, such as self-administration and allergic and infectious rhinitis, as well as an animal anaphylaxis model of severe hypotension, where neffy demonstrated a pharmacokinetic profile that is within the range of approved injection products and a pharmacodynamic response that is as good or better than injections. The increased pulse rate (PR) and blood pressure (BP) observed even one minute following the administration of neffy confirm the activation of α and ß adrenergic receptors, which are the key components of epinephrine's mechanism of action. The results suggest that neffy will provide a safe and effective needle-free option for the treatment of severe allergic reactions, including anaphylaxis.

Real-world outcomes in patients with chronic spontaneous urticaria receiving omalizumab: insights from a clinical practice survey.

OBJECTIVE: Chronic spontaneous urticaria (CSU) is a debilitating inflammatory skin condition, often impacting quality of life. International guidelines recommend omalizumab, an anti-immunoglobulin E antibody, for second-line treatment. Our objective was to understand patient characteristics associated with prescription of omalizumab, and assess real-world outcomes in patients with CSU treated with omalizumab. METHODS: We analyzed data from the Adelphi Real World CSU Disease Specific Programme, a cross-sectional survey with retrospective data collection (December 2020-October 2021) from physicians and patients with CSU in the United States. RESULTS: Data from allergists (n = 45), dermatologists (n = 51), and primary care physicians (PCPs; n = 20) were included. At the time of data collection, one-third of patients were receiving omalizumab (n = 220) and 67% were eligible for but not receiving omalizumab (n = 455). Using logistic regression, the odds of receiving omalizumab were higher in patients whose entire bodies were affected by hives [odds ratio (OR) = 2.551; 95% confidence interval (CI) 1.502-4.333; p < 0.001] or with deteriorating/unstable prognoses at treatment initiation [OR = 2.219; 95% CI 1.031-4.777; p = 0.042], and lower in patients managed by PCPs [OR = 0.276; 95% CI 0.130-0.584; p < 0.001]. Estimates from an inverse probability weighted regression adjustment model indicated that patients receiving omalizumab had higher treatment satisfaction, improvements in itching, hives, angioedema, insomnia, and anxiety, and lower impact on work productivity, compared with patients not receiving omalizumab. CONCLUSION: Around two-thirds of patients with CSU considered eligible for omalizumab were not receiving the guideline-recommended therapy. Patients receiving omalizumab had better real-world outcomes compared with patients not receiving omalizumab. Ensuring patients receive the most appropriate treatment could benefit patients with CSU.

People with a skin rash known as chronic spontaneous urticaria (also called long-lasting hives) have itchy spots that last longer than 6 weeks. People with long-lasting hives may be treated with a medicine called omalizumab to help their itching. We asked doctors why they gave some people omalizumab. We found that only one out of every three people with long-lasting hives were given omalizumab. Doctors gave some people omalizumab because they had long-lasting hives on their whole body or their hives were getting worse. Other people received omalizumab because they were seeing a specialist doctor (allergist) instead of a primary care physician (also called a general practitioner). When compared with people who received other medicines, people being treated with omalizumab had reduced itching, less anxiety, and better well-being. These findings could help doctors choose the right medicine for people with long-lasting hives.

A practical guide for implementing omalizumab therapy for food allergy.

The recent approval of omalizumab for the treatment of IgE-mediated food allergy is an important step forward for the millions of food allergy patients in the United States. Through the depletion of circulating IgE and the subsequent reduction of FcεR1 on key effector cells, patients increase their tolerance to food allergens. However, omalizumab does not permit patients to eat foods that they are allergic to with impunity. Rather, it protects them from most accidental exposures. In addition, omalizumab does not cure food allergy and has not demonstrated true immunomodulation. Thus, omalizumab might be a lifelong therapy for some patients. Furthermore, there are many important questions and issues surrounding the appropriate administration of omalizumab to treat food allergy, which we discuss. Managing treatment of patients with disease that falls outside the dosing range, assessing treatment response or nonresponse, addressing its appropriateness for patients older than 55, and determining whether immunotherapy plus omalizumab provides any advantage over omalizumab alone all need to be examined. Identifying appropriate patients for this therapy is critical given the cost of biologics. Indeed, not all food allergy patients are good candidates for this therapy. Also, when and how to stop omalizumab therapy in patients who may have outgrown their food allergy needs to be elucidated. Thus, although this therapy provides a good option for patients with food allergies, much information is needed to determine how best to use this therapy. Despite many unanswered questions and issues, we provide clinicians with some practical guidance on implementing this therapy in their patients.

The mental health burden of food allergies: Insights from patients and their caregivers from the Food Allergy Research & Education (FARE) Patient Registry.

Background: Food allergies impose a large psychosocial burden, including mental, emotional, and social aspects, on both patients and their caregivers. Patients, caregivers, and their families often experience anxiety, isolation, and fear around food allergies. Objective: To assess the real-world mental health burden of food allergies, using the Food Allergy Research & Education (FARE) Patient Registry (NCT04653324). Methods: Self-reported data from patients with food allergies, and their caregivers, were analyzed from the FARE Food Allergy History and Mental Health Concerns surveys. Odds ratios were also calculated as a measure of association between patient food allergy characteristics and the likelihood of having mental health concerns or a formal mental health diagnosis. Results: The FARE Patient Registry included 1680 patients/caregivers. Anxiety (54%) and panic (32%) were the most common emotions that patients reported as a result of eating the food that produced an allergic reaction. About two-thirds of patients reported mental health concerns related to food allergies (62%), including anxiety after an allergic reaction, anxiety about living with food allergies, and concerns about food avoidance. Caregivers also experienced fear for the safety of their children, and often sought mental health care to cope with worry related to caring for patients with food allergies. The likelihood of having food allergy-related mental health concerns was increased for patients experiencing more than 1 reaction per year (OR 1.68-1.90) and was lowered for patients having a formal mental health diagnosis (OR 0.43). Caregivers filling out the FARE survey for pediatric patients (OR 4.03) and experiencing food allergy-related mental health concerns (OR 2.36) were both significant predictors for having a formal mental health diagnosis. Conclusion: Our study highlights a continuing unmet need for mental health screening and support as part of the management of patients with food allergies.

Advancements in biologic therapy in eosinophilic asthma.

INTRODUCTION: Asthma encompasses a spectrum of phenotypes often categorized into two groups- type 2 high (T2 high) and type 2 low (T2 low). T2 high includes atopic and eosinophilic presentations whereas T2 low is non-atopic, non-eosinophilic, and oft associated with neutrophilic inflammation. Eosinophilic asthma is often driven by IgE, IL-4, IL-5, and IL-13 and TSLP. This can lead to eosinophilic inflammatory response in the airways which in turn can be used as target for treatment. AREAS COVERED: The article will focus on biologic therapy that is currently being used in eosinophilic asthma management in mainly the adult population including clinical trials and co-morbidities that can be treated using the same biologics. A review on asthma biologics for pediatric population has been reviewed elsewhere. EXPERT OPINION: Biological therapy for asthma targeting the IgE, IL-4, IL-5, IL-13, and TSLP pathways are shown to have benefit for the treatment of eosinophilic asthma, as exemplified in real-world studies. When choosing the right biological agent factors such as phenotype, comorbidities, and cost-effectiveness of the biologic agent must be taken into consideration.

Dupilumab in patients with chronic spontaneous urticaria (LIBERTY-CSU CUPID): Two randomized, double-blind, placebo-controlled, phase 3 trials.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a chronic inflammatory disease characterized by recurrent pruritic wheals (hives) and/or angioedema. Patients with CSU could remain symptomatic despite standard-of-care H1 antihistamines (H1-AH) or anti-IgE (omalizumab) treatment. Dupilumab blocks IL-4/IL-13 signaling and is approved for multiple type 2/atopic indications. OBJECTIVE: We conducted two phase 3, randomized, placebo-controlled, double-blind trials comparing dupilumab with placebo in patients with symptomatic CSU despite H1-AH. METHODS: In LIBERTY-CSU CUPID Study A, patients were omalizumab-naive (n = 138, aged ≥6 years). In Study B, patients were omalizumab-intolerant/incomplete responders (n = 108, aged ≥12 years). The primary end point was either change from baseline over 7 days in the Urticaria Activity Score (UAS7) or Itch Severity Score (ISS7) at week 24, with the other as a key secondary end point, depending on regional regulatory requirements. Studies were pooled for safety assessment. RESULTS: In Study A, UAS7 and ISS7 improved with dupilumab versus placebo (difference -8.5 [95% CI, -13.2 to -3.9; P = .0003] and -4.2 [95% CI, -6.6 to -1.8; P = .0005]). In Study B, tested at α = 0.043 after interim analysis, UAS7 improved (difference -5.8 [95% CI, -11.4 to -0.3; P = .0390]), with a numerical trend in ISS7 (difference -2.9 [95% CI, -5.7 to -0.07; nominal P = .0449, not significant]). Pooled safety data were consistent between dupilumab and placebo and with the known dupilumab safety profile. CONCLUSIONS: Dupilumab reduced urticaria activity by reducing itch and hives severity in omalizumab-naive patients with CSU uncontrolled with H1-AH. Although the primary end point for Study B was not met, dupilumab effects were small in patients who were omalizumab-intolerant/incomplete responders.

Dupilumab Reduces Exacerbations Independent of Changes in Biomarkers in Moderate-to-Severe Asthma.

BACKGROUND: Changes from baseline in fractional exhaled nitric oxide (FeNO) and blood eosinophil count (Eos) may be related to efficacy outcomes in dupilumab-treated patients with moderate-to-severe asthma. OBJECTIVE: This post hoc analysis investigated biomarker changes in placebo- and dupilumab-treated patients with uncontrolled moderate-to-severe asthma enrolled in QUEST (NCT02414854). METHODS: Spline analyses of annualized severe exacerbation rate (AER) and change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) at week 52 were performed as a function of the fold change in FeNO at week 52 and the maximum fold change in Eos over weeks 0-12 (also change from baseline in pre-BD FEV1 at week 12). RESULTS: The combined placebo and dupilumab groups comprised 638 and 1264 patients, respectively. FeNO levels declined rapidly by week 2 and then gradually to week 52 in patients treated with dupilumab versus placebo; Eos, after initially increasing with dupilumab, declined slightly from baseline in both treatment groups. AER during QUEST showed no significant association with the change in biomarkers in either treatment group. The change from baseline in pre-BD FEV1 at week 52 was inversely associated with the fold change in FeNO in both groups, with a significant difference between the dupilumab and placebo curves (P = .014), and was positively associated with the fold change in Eos in both groups (P = .022). CONCLUSIONS: Relative changes in FeNO and Eos were not associated with AER, regardless of treatment arm. However, changes in both biomarkers showed a predictive value for lung function improvement; for FeNO, this was specific to the dupilumab treatment arm.

Efficacy of 300 IR house dust mite immunotherapy as a function of disease activity: Tertile analysis in clinical trials.

BACKGROUND: The symptoms of house dust mite (HDM)-induced allergic rhinitis (AR) vary with changes in exposure related to the weather or the domestic environment. In allergen immunotherapy (AIT) studies, a certain level of AR disease activity is necessary to demonstrate treatment efficacy; the latter can be underestimated if a substantial proportion of the patient population is weakly symptomatic. OBJECTIVE: To better estimate the real treatment effect of a HDM sublingual AIT (SLIT) tablet, we analysed the results of natural field studies in detail by applying a tertile approach. METHODS: We used data from three randomised, controlled trials (RCT) in a total of 2585 patients with AR treated with the 300 index of reactivity (IR) HDM SLIT-tablet or placebo. The study centres were grouped into tertiles according to the level of combined symptom and medication scores in patients in the placebo group. In each tertile, the difference between SLIT and placebo was assessed through an analysis of covariance. RESULTS: In the three RCTs, combined scores were found to be similar in the SLIT and placebo groups in the low tertiles. The treatment effect of the 300 IR HDM tablet increased in the medium and high tertiles, with notably significant differences versus placebo in the highest tertile and greater (ranging from -21% to -39%) than in the entire study population (-13% to -20%). The positive relationship between treatment efficacy and the combined score in each tertile was independent of the RCT and the score used. CONCLUSION AND CLINICAL RELEVANCE: Application of the tertile approach to AIT studies in a field in which many variables interact strongly might provide more accurate and meaningful measurements of efficacy and benefit for patients, better reflecting their real-life condition.

The clinical burden of food allergies: Insights from the Food Allergy Research & Education (FARE) Patient Registry.

Background: Food allergies are serious and potentially life-threatening, and often place a large burden on patients and their caregivers, including impacts on quality of life. Objective: To assess the real-world patient burden of food allergies, using self-reported data available from the Food Allergy Research & Education (FARE) Patient Registry (NCT04653324). Methods: The FARE Patient Registry is voluntary and captures real-world experiences of adults and pediatric patients in the United States, and their caregivers, through a series of surveys assessing patient health and experiences with food allergies. Self-reported data were descriptively analyzed. Results: The FARE study cohort included 5587 patients with food allergies; 82% had multiple food allergies and 62% were aged <18 years. About half of the patients were first diagnosed by an allergist/immunologist (53%), most commonly with a skin prick test (71%) or a serum immunoglobulin E test (62%). This analysis found that food allergies (most commonly peanut [66%], tree nuts [61%], egg [43%], and milk [37%]) impart a large clinical burden on patients, many of whom experience food-related allergic reactions and comorbidities. Many patients experienced >1 food-related allergic reaction per year (42%), with 46% experiencing food-induced anaphylaxis. Half of all food-related allergic reactions occurred at home. Accidental exposures to food allergens were experienced by 77% of patients. The most common allergic comorbidities reported by patients with food allergies were atopic dermatitis (48%), asthma (46%), and allergic rhinitis (39%). The clinical burden of food allergies were found to be greater in patients with multiple food allergies, and different for adults versus pediatric patients. Conclusion: This is the first study to assess patient experience and disease burden information from patients contributing to the FARE Patient Registry, thus providing a unique insight into the lives of patients in the United States with food allergies. These insights may assist clinicians and other public health stakeholders in the management of patients with food allergies.

Real-world association between systemic corticosteroid exposure and complications in US patients with severe asthma.

BACKGROUND: Systemic corticosteroid (SCS) use remains widespread among patients with severe asthma, despite associated complications. OBJECTIVE: Evaluate the association between cumulative SCS exposure and SCS-related complications in severe asthma. METHODS: This retrospective, longitudinal study used claims data from the Optum Clinformatics Data Mart database (GSK ID: 214469). Eligible patients (≥ 12 years old) had an asthma diagnosis and were divided into two cohorts: SCS use and non/burst-SCS use. Patients in the SCS use cohort had a claim for a daily prednisone-equivalent dose ≥ 5 mg SCS following ≥ 6 months of continuous SCS use; those in the non/burst-SCS cohort had no evidence of continuous SCS use and had a non-SCS controller/rescue medication initiation claim. For each cohort, the date of the qualifying claim was the index date. SCS users were further stratified by SCS use during each quarter of follow-up: low (≤ 6 mg/day), medium (> 6-12 mg/day), high (> 12 mg/day), and continuous high (≥ 20 mg/day for 90 days). SCS-related complications were evaluated in the quarter following SCS exposure. The adjusted odds ratios (OR) of experiencing SCS-related complications during follow-up in each of the SCS use groups versus the non/burst SCS cohort were calculated using generalized estimating equations models. RESULTS: SCS and non/burst-SCS use cohorts included 7473 and 89,281 patients (mean follow-up: 24.6 and 24.2 months), respectively. Compared with the non/burst-SCS use cohort, medium, high, and continuous high SCS use was associated with greater odds of any SCS-related complication (adjusted OR [95% confidence interval]: 1.30 [1.21, 1.39], 1.49 [1.35, 1.64] and 1.63 [1.40, 1.89], respectively) including increased acute gastrointestinal, cardiovascular, and immune system-related complications, and chronic cardiovascular, metabolic/endocrine, central nervous system, bone-/muscle-related, ophthalmologic, and hematologic/oncologic complications. Low-dose SCS use was also associated with significantly increased odds of acute gastrointestinal and immune system-related complications, and chronic bone-/muscle-related and hematologic/oncologic complications versus the non/burst-SCS use cohort. CONCLUSION: SCS use, even at low doses, is associated with increased risk of SCS-related complications among patients with severe asthma.

Effectiveness of omalizumab across different dosing regimens in patients with moderate-to-severe allergic asthma.

For patients with moderate-to-severe persistent allergic asthma, omalizumab is approved for subcutaneous administration according to a recommended dosing table based on weight and total immunoglobulin E (IgE) level. The aim of this analysis was to assess asthma outcomes including quality of life in patients with allergic asthma initiated on omalizumab in the PROSPERO trial; patients were stratified by where their IgE and body weight fell on the approved dosing table. Patient groups were defined as Inside Dosing Table: patients whose IgE and weight fell within the approved dosing table (n = 506); Insufficient Data to Recommend a Dose: patients who fell into the section of the approved dosing table where not enough clinical data were available to make dosing recommendations (n = 72); and Outside Dosing Table: patients who fell outside the approved dosing table due to baseline IgE and/or weight (n = 209). Overall, asthma and quality of life outcomes were improved after omalizumab initiation for both patients who fall within the recommended dosing table or those who fall outside the recommended dosing table. Our results suggest that omalizumab treatment may be effective in a wide range of patients with moderate-to-severe allergic asthma. ClinicalTrials.gov identifier NCT01922037.

Clinical benefits with 300 IR HDM SLIT tablet in Europeans with house dust mite allergic rhinitis: Post hoc analysis of a large phase 3 trial.

Background: House dust mite (HDM)-induced allergic rhinitis (AR) is a major cause of allergic respiratory disease. The efficacy and safety of the 300 IR HDM sublingual immunotherapy (SLIT) tablet in patients with moderate-to-severe HDM-AR was confirmed in a large, international, phase 3 randomized controlled trials (RCTs). Here, we analyzed the results in the European population. Methods: Data from 91 European centers that participated in the international, double-blind, RCT (EudraCT 2014-004223-46, NCT02443805) with the 300 IR HDM SLIT tablet versus placebo over 12 months were analyzed post hoc. The treatment effect in European adults and adolescents was notably assessed through the European Academy of Allergy and Clinical Immunology (EAACI)-recommended combined symptom and medication score (CSMS0-6, pre-defined endpoint) and the total combined rhinitis score (TCRS0-24, post hoc endpoint, also balanced) during the primary evaluation period (4 weeks at the end of treatment period) using analysis of covariance (ANCOVA). Results: There were 818 patients who comprised the modified full analysis set in Europe. Over the primary period, the differences in CSMS0-6 and TCRS0-24 between the 300 IR and placebo groups were statistically significant (p < 0.0001): -0.32 (95%CI [-0.46; -0.17]) and -1.28 (95%CI [-1.63; -0.94]), respectively, with relative differences of -20.9% and -21.2%. All post hoc and the rhinoconjunctivitis quality of life endpoints were significantly improved with 300 IR versus placebo. The 300 IR HDM tablet was generally well tolerated. Conclusion: This RCT sub-analysis confirmed the 300 IR HDM SLIT tablet is an effective and safe treatment for European adults and adolescents with HDM-AR with clinically meaningful benefits from the patients' perspective. Trial registration: NCT02443805. Registered on April 29, 2015./EudraCT 2014-004223-46. Registered on September 16, 2015.