Pharmacoequity and Biologics in the Allergy Clinic: Providing the Right Care, at the Right Time, Every Time, to Everyone.

Pharmacoequity refers to equity in access to pharmacotherapy for all patients and is an especially large barrier to biologic agents in patients with allergic diseases. Value-based care models can prompt clinicians to address social determinants of health, promoting pharmacoequity. Pharmacoequity is influenced by numerous factors including socioeconomic status, which may be mediated through insurance status, educational attainment, and access to specialist care. In addition to lower socioeconomic status, race and ethnicity, age, locations isolated from care systems, and off-label indications for biologic agents all constitute barriers to pharmacoequity. Whereas pharmaco-inequity is more apparent for expensive biologics, it also affects many other allergy treatments including epinephrine autoinjectors and SMART for asthma. Current programs aimed at alleviating cost barriers are imperfect. Patient assistance programs, manufacturer-sponsored free drug programs, and rebates often increase the complexity of care, with resultant inequity, particularly for patients with lower health literacy. Ultimately, single silver-bullet solutions are elusive. Long-term improvement instead requires a combination of research, advocacy, and creative problem-solving to design more intelligent and efficient systems that provide timely access to necessary care for every patient, every time.

Social Determinants of Health and COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected disadvantaged populations. Many of the factors related to the disproportionate impact on underserved communities are related to social determinants of health, defined by the World Health Organization as the nonmedical factors that influence health outcomes. They include the wider set of forces and systems shaping the conditions of daily life. This work explores the interrelationships between social determinants of health and access to care, health care professional and supply shortages, social and environmental factors, health behaviors, vaccine uptake, and treatment options on COVID-19 health outcomes. Increased awareness of inequities, learning from failures, and leveraging new opportunities to partner with key stakeholders in underserved communities create empowerment and preparedness to face new challenges.

Updated guidance regarding the risk of allergic reactions to COVID-19 vaccines and recommended evaluation and management: A GRADE assessment and international consensus approach.

This guidance updates 2021 GRADE (Grading of Recommendations Assessment, Development and Evaluation) recommendations regarding immediate allergic reactions following coronavirus disease 2019 (COVID-19) vaccines and addresses revaccinating individuals with first-dose allergic reactions and allergy testing to determine revaccination outcomes. Recent meta-analyses assessed the incidence of severe allergic reactions to initial COVID-19 vaccination, risk of mRNA-COVID-19 revaccination after an initial reaction, and diagnostic accuracy of COVID-19 vaccine and vaccine excipient testing in predicting reactions. GRADE methods informed rating the certainty of evidence and strength of recommendations. A modified Delphi panel consisting of experts in allergy, anaphylaxis, vaccinology, infectious diseases, emergency medicine, and primary care from Australia, Canada, Europe, Japan, South Africa, the United Kingdom, and the United States formed the recommendations. We recommend vaccination for persons without COVID-19 vaccine excipient allergy and revaccination after a prior immediate allergic reaction. We suggest against >15-minute postvaccination observation. We recommend against mRNA vaccine or excipient skin testing to predict outcomes. We suggest revaccination of persons with an immediate allergic reaction to the mRNA vaccine or excipients be performed by a person with vaccine allergy expertise in a properly equipped setting. We suggest against premedication, split-dosing, or special precautions because of a comorbid allergic history.

Optimization of care for patients with hereditary angioedema living in rural areas.

BACKGROUND: People living in rural areas of the United States experience greater health inequality than individuals residing in urban or suburban locations and encounter several barriers to obtaining optimal health care. Health disparities are compounded for patients with rare diseases such as hereditary angioedema (HAE), an autosomal dominant genetic disorder characterized by recurrent, severe abdominal pain and life-threatening oropharyngeal or laryngeal swelling. OBJECTIVE: To explore the challenges of managing patients with HAE in rural areas and suggest possible improvements for optimizing care. DATA SOURCES: PubMed was searched for articles on patient care management, treatment challenges, rural health, and HAE. STUDY SELECTIONS: Relevant articles were selected and reviewed. RESULTS: Challenges in managing HAE in the rural setting were identified, including obtaining a diagnosis of HAE, easy access to a physician with expertise in HAE, continuity of care, availability of telemedicine services, access to approved HAE therapies, patient education, and economic barriers to treatment. Ways to improve HAE patient care in rural areas include health care provider recognition of the patient with undiagnosed HAE, development of individualized management plans, expansion of telemedicine, effective care at the local level, appropriate access to HAE medication, and increased awareness of patient support and advocacy groups. CONCLUSION: For patients with HAE living in rural areas, optimal care is complicated by health disparities. Given the scarcity with which these topics have been covered in the literature to date, it is intended that this article will serve as the impetus for a range of further initiatives focused on improving access to care.

Workers' compensation prescription medication patterns and associated outcomes.

BACKGROUND: Opioid use in the treatment of musculoskeletal injuries is a complex decision where benefits must be balanced with risk. Previous research has shown an association between higher opioid doses and adverse health effects. The study's objective was to investigate whether opioid prescriptions are associated with increased costs and deaths through an injury mechanism or as a direct result of the opioid prescription. METHODS: Data for 144,553 deidentified Ohio Bureau of Workers' Compensation claims from 2010 to 2014 with shoulder, knee, and low back injuries were obtained and followed until 2016. Each claim had associated prescription information. Injury claims were further classified using the allowed diagnoses by single or multiple body areas affected and injury severity ("simple" or "complex"). The outcome variables were medical and indemnity costs, lost days, MaxMED (maximum claim-prescribed daily morphine equivalent dose), and death status. Association between maximum opioid dose with deaths was determined by logistic regression analysis. RESULTS: Several outcome variables, including claim medical and indemnity costs, and the likelihood of claimant death, showed significant associations with the MaxMED. In the analysis of claim deaths, these associations held for all claim types (except complex), even after adjusting for age, gender, surgery, and lost time. CONCLUSION: The association between increasing opioid doses and deaths for low-severity diagnoses was disturbing given the lack of demonstrated efficacy of opioids for treatment of minor injuries. A focus on provider education, increased utilization of non-opioids, and early intervention for minor soft-tissue injuries could reduce claims costs, disability, and future deaths.

The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management: A Systematic Review, Meta-Analysis, GRADE Assessment, and International Consensus Approach.

Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the World Health Organizstion (WHO) global coronavirus database, and the gray literature (inception, March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases per million (n = 41,000,000 vaccinations; 95% confidence interval [95% CI] 4.02-15.59; 26 studies, moderate certainty), the incidence of 0.15 cases per million patient-years (95% CI 0.11-0.2), and the sensitivity for PEG skin testing is poor, although specificity is high (15 studies, very low certainty). We recommend vaccination over either no vaccination or performing SARS-CoV-2 vaccine/excipient screening allergy testing for individuals without history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient, and a shared decision-making paradigm in consultation with an allergy specialist for individuals with a history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient. We recommend further research to clarify SARS-CoV-2 vaccine/vaccine excipient testing utility in individuals potentially allergic to SARS-CoV2 vaccines or their excipients.

Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis.

Anaphylaxis is an acute, potential life-threatening systemic allergic reaction that may have a wide range of clinical manifestations. Severe anaphylaxis and/or the need for repeated doses of epinephrine to treat anaphylaxis are risk factors for biphasic anaphylaxis. Antihistamines and/or glucocorticoids are not reliable interventions to prevent biphasic anaphylaxis, although evidence supports a role for antihistamine and/or glucocorticoid premedication in specific chemotherapy protocols and rush aeroallergen immunotherapy. Evidence is lacking to support the role of antihistamines and/or glucocorticoid routine premedication in patients receiving low- or iso-osmolar contrast material to prevent recurrent radiocontrast media anaphylaxis. Epinephrine is the first-line pharmacotherapy for uniphasic and/or biphasic anaphylaxis. After diagnosis and treatment of anaphylaxis, all patients should be kept under observation until symptoms have fully resolved. All patients with anaphylaxis should receive education on anaphylaxis and risk of recurrence, trigger avoidance, self-injectable epinephrine education, referral to an allergist, and be educated about thresholds for further care.

Optimizing Value in the Evaluation of Chronic Spontaneous Urticaria: A Cost-Effectiveness Analysis.

BACKGROUND: Chronic spontaneous urticaria (CSU) affects approximately 1% of the general population. The cost-effectiveness of routine laboratory testing for secondary causes of CSU has not been formally evaluated. OBJECTIVE: To characterize the cost-effectiveness of routine laboratory screening in adults with CSU. METHODS: A Markov model using cohort analysis and microsimulations was created for adult patients aged 20 years, over a 10-year time horizon, randomized to receive screening laboratory testing or a no-testing approach. Laboratory results were derived from a previously published retrospective analysis of adult patients with CSU. Cost-effectiveness was evaluated at a willingness to pay threshold of $100,000/quality-adjusted life-year using the incremental cost-effectiveness ratio (ICER) in patients with untreated CSU, and patients treated with antihistamines, cyclosporine, or omalizumab. RESULTS: Average laboratory costs per simulated patient with CSU were $573 (standard deviation [SD], $41), with only 0.16% (SD, 3.99%) of tests resulting in improved clinical outcomes. Testing costs per laboratory-associated positive outcome were $358,052 (no therapy), $357,576 (antihistamine therapy), $354,115 (cyclosporine), and $262,121 (omalizumab). Screening tests were not cost-effective, with ICERs of $856,905 (no therapy), $855,764 (antihistamine therapy), $847,483 (cyclosporine), and $627,318 (omalizumab). In the omalizumab-treated subgroup, testing could be cost-effective below $220 or if it resulted in a 0.73% rate of CSU resolution. From a simulated US population perspective, nation-wide screening costs could reach $941,750,741 to $1,833,501,483. CONCLUSIONS: In CSU, the likelihood of clinical improvement from laboratory testing is very low, and testing is not cost-effective. These data support recommendations to not routinely perform laboratory testing in patients with CSU with otherwise normal histories and physical evaluations.

Penicillin allergy skin testing as an antibiotic stewardship intervention reduces alternative antibiotic exposures in hematopoietic stem cell transplant recipients.

BACKGROUND: Antibiotic allergy de-labeling using penicillin allergy skin testing (PAST) can reduce the use and cost of alternative, non-ß-lactam antibiotics in general inpatient populations. This strategy's role in hematopoietic stem cell transplant (HSCT) recipients is unclear. METHODS: This study aimed to determine the effect of a pre-transplant PAST protocol on antibiotic use, days of therapy (DOT), and cost in an immunocompromised population at a single center from 7/1/2010-2/1/2019. Patients who received chimeric antigen receptor (CAR) T-cell therapy and those who underwent transplantation in the outpatient setting were excluded. RESULTS: Of 1560 patients who underwent inpatient HSCT during the study period, 208 reported ß-lactam allergy (136/844 [16%] pre- and 72/716 [10%] post-implementation; P < .001). PAST was performed on 7% and 54% of HSCT recipients pre- and post-implementation, respectively. Only two positive PAST were noted. There were no adverse reactions to PAST. There were no significant differences in the disease and transplant characteristics between the two groups. Days of therapy and cost of alternative antibiotics significantly decreased post-implementation (mean 788 vs 627 days, P = .01; mean $24 425 vs $17 518, P = .009). CONCLUSION: Penicillin allergy skin testing adjudicates reported ß-lactam allergy in HSCT recipients, lowering use, DOT, and cost of alternative antibiotics and promoting effective formulary agents to treat immunocompromised HSCT recipients.

Severe asthma: epidemiology, burden of illness, and heterogeneity.

BACKGROUND: Patients with severe persistent asthma comprise only 5-10 % of the total asthma population, but account for a large proportion of asthma morbidity and health care expenditures. Among patients with severe asthma, higher costs can be expected in association with not well or poorly controlled asthma. OBJECTIVE: To summarize the evidence concerning the epidemiology, burden, and heterogeneity of severe asthma. METHODS: A literature search was performed to identify citations using the terms "severe asthma" and "epidemiology", "asthma control", "asthma" and "heterogeneity". RESULTS: Successful management of patients with severe asthma continues to be a major unmet need. One of the barriers to successful management is the heterogeneity of asthma. Asthma is not one disease; it is a disorder that can be subdivided into a number of different phenotypes and endotypes. A revised paradigm for asthma management, that entails categorization of asthma patients via use of "biomarkers", and prescribing targeted therapy, will supplant what has been a "one size fits all" approach to asthma management. CONCLUSION: The novel approach to asthma management, in which therapy will be more mechanism-specific based on phenotype/endotype, offers the potential for improved asthma care outcomes - particularly for patients with severe persistent asthma who are not well or poorly controlled.

Environmental assessment and exposure reduction of cockroaches: a practice parameter.

This parameter was developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing "Environmental assessment and remediation: a practice parameter." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single person, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion. The findings and conclusions in this manuscript are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC).

Medical costs and adherence in patients receiving aqueous versus pressurized aerosol formulations of intranasal corticosteroids.

Intranasal corticosteroid (INS) formulations have different sensory attributes that influence patient preferences, and thereby possibly adherence and health outcomes. This study compares health care use and costs and medication adherence in matched cohorts of patients with allergic rhinitis (AR) using a chlorofluorocarbon-propelled pressurized metered-dose inhaler (pMDI) or aqueous intranasal corticosteroid (A-INS). Florida Medicaid retrospective claims analysis was performed of enrollees aged ≥12 years with at least 1 year of continuous enrollment before their initial AR diagnosis, 1 year for continuous enrollment before their index INS claim, and 18 months of continuous enrollment after their index INS claim during which they received either pMDI or A-INS. pMDI and A-INS patients were matched 1:2 using propensity scores. Nonparametric analyses compared outcomes between matched cohorts at 6, 12, and 18 months of follow-up. A total of 585 patients were matched (pMDI = 195, A-INS = 390). pMDI patients were more adherent to INS, as reflected in their higher median medication possession ratio (53.2% versus 32.7%; p < 0.0001) and fewer median days between fills (73 days versus 111 days; p = 0.0003). Significantly lower median per patient pharmacy fills (34.0 versus 50.5; p < 0.05) and costs ($1282 versus $2178; p < 0.01) were observed among pMDI patients versus A-INS patients 18 months after INS initiation and were maintained when analyses excluded INS fills. Adherence to INS and health care utilization and costs following INS initiation for AR differed by type of formulation received. Our findings suggest patient preferences for INS sensory attributes can drive adherence and affect disease control, and ultimately impact health care costs.

Asthma in African Americans: what can we do about the higher rates of disease?

African Americans not only have a higher prevalence of asthma than whites, they also are encumbered with higher rates of asthma-associated morbidity and death. Factors such as genetics, socioeconomic status, health maintenance behaviors, air quality, and obesity likely contribute in combination to these burdens. Further work is needed to better understand these complex risk factors. To remedy these disparities, we need to ensure that patients at higher risk are given proper care and the knowledge to control their asthma.

Utility of routine laboratory testing in management of chronic urticaria/angioedema.

BACKGROUND: Laboratory tests are routinely ordered to identify or rule out a cause in patients with chronic urticaria/angioedema (CUA). The results of these tests are usually within normal limits or unremarkable. OBJECTIVE: To investigate the proportion of abnormal test results in patients with CUA leading to a change in management and in outcomes of care. METHODS: Retrospective analysis of a random sample of adult patients with CUA from 2001-2009. RESULTS: Cases totaled 356: 166 with urticaria and angioedema (AE), 187 with urticaria, and 3 with only AE. Patients were predominately women (69.1%) and white (75.6%), with a mean age of 48 ± 15 years. Abnormalities were commonly seen in complete blood counts (34%) and in complete metabolic panels (9.4%). Among the 1,872 tests that were ordered, results of 319 (17%) were abnormal. Of 356 patients, 30 underwent further testing because of abnormalities in laboratory work. This represented 30 of 1,872 tests (1.60%). Only 1 patient benefited from a subsequent change in management. CONCLUSIONS: Laboratory testing in CUA patients referred for an Allergy and Immunology evaluation rarely lead to changes in management resulting in improved outcomes of care.

Systemic reactions associated with subcutaneous allergen immunotherapy: timing and risk assessment.

BACKGROUND: Subcutaneous allergen immunotherapy (SCIT) is associated with risk of systemic reaction. Although risk factors have been identified, the incidence of immunotherapy-related systemic reactions has not changed in recent years. OBJECTIVES: To examine patterns of systemic reaction and determine whether risk of systemic reaction from SCIT is associated with patterns of response to skin tests to inhalant allergens recorded before receiving SCIT. METHODS: We carried out a retrospective review from January 2001 to December 2007. Patterns of systemic reaction from immunotherapy were examined. Cases were matched with controls by age (±10 years), sex, and time of injection (±1 week) to determine whether a pattern of more than 33% 3+ and 4+ skin test responses is associated with elevated risk for systemic reaction. RESULTS: Rate of systemic reaction from SCIT was 0.28% (46/16,375) per injection visit. Twenty patients had 46 systemic reactions. All severe reactions occurred within 30 minutes. The estimated odds of systemic reaction were almost 6 times higher for patients with more than 33% 3 to 4+ positive skin tests (OR = 5.83; 95%CI: 1.23-27.59, P = .026). For each additional 4+ skin test, the estimated odds for systemic reaction increased by 17% (P = .020). CONCLUSIONS: A small number of patients receiving SCIT account for a large proportion of systemic reactions. Skin test patterns demonstrating a greater number of larger skin tests responses to inhalant skin testing are associated with significantly elevated risk for systemic reaction in patients receiving SCIT.