The Cost-Effectiveness of Omalizumab for Treatment of Food Allergy.

BACKGROUND: Omalizumab is a newly FDA approved anti-IgE therapy for allergen agnostic treatment of single or multiple food allergies in patients ages >1 year. OBJECTIVE: Evaluate the cost-effectiveness of omalizumab as a food allergy treatment. METHODS: Health and economic outcomes were evaluated in Markov cohorts of simulated food allergic infants randomized to receive omalizumab using a 15-year time horizon. Monte Carlo simulation was used (n=40,000 subjects) to evaluate cost-effectiveness from a societal perspective, incorporating both a family-level and individual-level analysis. Family-level analysis was included to incorporate broad perspective for health utility change, given treatment effects likely benefit all parties at home (e.g., caregivers, siblings, spouses), not just the patient, representing the sum of changes in all such persons. Supplemental analyses explored lower omalizumab cost and home initiation. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: In the family-level cohort analysis, omalizumab exceeded cost-effectiveness thresholds ($185,183/QALY). Comparing the omalizumab strategy (OMA) to the non-omalizumab strategy (NOMA), the cost of OMA exceeded NOMA ($315,020 vs $136,609) with greater incremental effectiveness (12.668 QALY vs 11.699 QALY). In the individual-level analysis, the cost-effectiveness of OMA was $573,698/QALY. In base-case assessments, OMA was cost-effective (WTP, $100,000/QALY) at a health state utility improvement of 0.265. OMA's value-based cost ranged from $14,166-$23,791 when considered at the individual and family-unit levels. Requiring OMA administration in-clinic was not cost-effective (ICER, $260,239). CONCLUSIONS: In the base-case and at current pricing, omalizumab is not cost-effective, but could be at a lower retail price or if use creates large health utility shifts in the family and patient.

A nurse-driven penicillin allergy risk score in the preoperative setting was associated with increased cefazolin use perioperatively.

STUDY OBJECTIVE: To characterize and assess the effects of a preoperative, nurse-driven penicillin allergy risk stratification tool on rates of perioperative cefazolin and second-line antibiotic use. DESIGN: Quasi-experimental quality improvement study of penicillin-allergic surgical patients undergoing procedures for which cefazolin is indicated. SETTING: Outpatient Perioperative Care Clinic (PCC) for preoperative surgical patients at a tertiary care center. PATIENTS: 670 and 1371 adult penicillin-allergic PCC attendants and non-attendants, respectively. INTERVENTION: A paper penicillin allergy risk stratification questionnaire was administered during the PCC visit. Nurses were educated on its use. MEASUREMENTS: Antibiotic (cefazolin, clindamycin, vancomycin) use rates in the 24 months before and 17 months after intervention implementation in November 2020 (November 2018 - April 2022) were assessed in penicillin-allergic PCC attendants with statistical process control charts. Multivariable logistic regression assessed antibiotic use rates pre- and post-intervention adjusting for age, sex, surgical specialty and penicillin allergy history severity. Similar analyses were done in penicillin-allergic PCC non-attendants. MAIN RESULTS: Of 670 penicillin-allergic PCC attendants, 451 (median [IQR] age, 66 (Sousa-Pinto et al., 2021 [14])) were analyzed pre-intervention and 219 (median [IQR] age, 66 (Mine et al., 1970 [13])) post-intervention. One month after implementation, process measures demonstrated an upward shift in cefazolin use for PCC attendants versus no shift or other special cause variation for PCC non-attendants. There were increased odds of cefazolin use (aOR 1.67, 95% CI [1.09-2.57], P = 0.019), decreased odds of clindamycin use (aOR 0.61, 95% CI [0.42-0.89], P = 0.010) and decreased odds of vancomycin use (aOR 0.56, 95% CI [0.35-0.88], P = 0.013) in PCC attendants post-intervention. This effect did not occur in PCC non-attendants. There was no increase in perioperative anaphylaxis post-intervention. CONCLUSIONS: A simple penicillin allergy risk stratification tool implemented in the preoperative setting was associated with increased use of cefazolin and decreased rates of second-line agents post implementation.

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.

Twice-Daily Proton Pump Inhibitor Induces Higher Remission Rate in Eosinophilic Esophagitis Than Once-Daily Regimen Regardless of Total Daily Dose.

INTRODUCTION: The optimal proton pump inhibitor (PPI) regimen for eosinophilic esophagitis (EoE) is unclear. We compared histologic response rates of different dosing combinations. METHODS: A total of 305 patients with newly diagnosed EoE received standard (omeprazole 20 mg daily), once-daily moderate (40 mg daily), twice-daily moderate (20 mg twice daily), or high (40 mg twice daily) dose PPI for ≥8 weeks. RESULTS: Approximately 42.3% achieved histologic response to PPI, with higher rates for twice-daily (moderate 52.8%/high 54.3%) than once-daily (standard 11.8%/moderate 10%) dosing ( P < 0.0001). On multivariable analysis, twice-daily moderate (adjusted odds ratio 6.75, confidence interval 2.53-18.0, P = 0.0008) and high (adjusted odds ratio 12.8, confidence interval 4.69-34.8, P < 0.0001) doses independently predicted histologic response. DISCUSSION: Twice-daily PPI is associated with higher EoE histologic response rates than once-daily regimen.

Allergic phenotype identified on allergen testing is associated with proton pump inhibitor nonresponse in eosinophilic esophagitis.

BACKGROUND AND AIM: Food/environmental allergens have been associated with eosinophilic esophagitis (EoE); however, the correlation between allergy profiles and disease responsiveness to proton pump inhibitor (PPI) therapy remains unclear. We aimed to assess the association between food/environmental allergies identified on allergen testing and histologic response to PPI in patients with treatment-naive EoE. METHODS: Adults with newly diagnosed EoE who underwent formal testing for food/environmental allergies at a tertiary center were included. All patients underwent twice-daily PPI for 8 weeks with subsequent repeat endoscopy and biopsy to assess histologic response. Patients with <15 eosinophils/hpf on post-PPI mucosal biopsies were classified as responders (PPI-r-EoE), while those with ≥15 eosinophils/hpf were nonresponders (PPI-nr-EoE). RESULTS: Sixty-one patients met inclusion criteria (21 PPI-r-EoE vs 40 PPI-nr-EoE). Demographic, clinical, and endoscopic finding variables were similar between groups. Positive food allergen test was more prevalent among PPI-nr-EoE patients (82.5% vs 42.9%, P = 0.003). On multivariable analysis, positive food allergen testing remained an independent predictor for PPI nonresponse (aOR 0.15, CI: 0.04-0.58, P = 0.0006). Positive environmental allergen testing was highly prevalent, with no significant differences between groups (77.5% vs 95.2%, P = 0.14). However, higher number of positive environmental allergens (23.3% [≥5 allergens] vs 73.3% [<5 allergens], P = 0.003) and specific aeroallergens correlated with PPI-nr-EoE. CONCLUSION: Positive food allergy testing and increased environmental allergens predicted lower likelihood of histologic response to PPI in EoE. Our findings support an allergic phenotype of EoE that may less likely respond to PPI therapy. Formal allergen testing may play a role in therapy selection and tailored management in EoE.

Pearls for practice from the 2022 joint task force drug allergy practice parameter.

PURPOSE OF REVIEW: To review updated recommendations in the 2022 Drug Allergy Practice Parameters for the evaluation and management of drug hypersensitivity reactions. RECENT FINDINGS: Adverse drug reactions have become increasingly prominent with the advent of new and emerging pharmacologic therapies. Hypersensitivity reactions encompass a significant proportion of adverse drug reactions and negatively impact both the individual patient and overall health system. Reactions are heterogeneous in presentation and may be immediate (onset of symptoms ≤6 h) or delayed (onset of symptoms >6 h to months) after drug exposure. The 2022 Drug Allergy Practice Parameter provides consensus-based statements for evaluation of hypersensitivity reactions to antibiotics, NSAIDs, cancer chemotherapies, immune checkpoint inhibitors, biologics, and excipients. In general, the guideline highlights the importance of patient history in elucidating the phenotype and severity of the index reaction. Drug challenge remains the gold standard for diagnosis and is increasingly favored over skin testing in patients with nonsevere, nonanaphylactic drug reaction histories. SUMMARY: The 2022 Drug Allergy Practice Parameter provides an updated framework for physicians to reference in clinical practice when managing patients with drug hypersensitivity reactions.

Assessment of the clinical and allergy profiles of PPI responsive and non-responsive eosinophilic esophagitis.

A subset of patients with eosinophilic esophagitis (EoE) respond to proton-pump inhibitor (PPI) therapy, however they cannot be distinguished prior to PPI trial and the mechanism of PPI response remains unclear. Improved understanding of the distinct patient phenotypes in PPI-responsive EoE (PPI-r-EoE), PPI-non-responsive EoE (PPI-nr-EoE) and erosive esophagitis (EE) may help guide management. The aim of this paper is to compare the clinical and allergy profiles of PPI-r-EoE versus PPI-nr-EoE and EE. This was a retrospective case-control study of EoE patients (>15 eos/hpf on esophageal biopsies) at a tertiary center. EE controls were identified from the pathology database. EoE patients were classified as PPI-r-EoE or PPI-nr-EoE based on histologic response to twice-daily PPI for ≥8 weeks. Patient demographics, comorbidities, symptoms, allergy history and endoscopic findings were recorded. Univariate analyses were performed using the Fisher-exact test or t-test. Multivariable analyses were performed using logistic regression. In all, 104 EoE (57 PPI-r-EoE/47 PPI-nr-EoE) and 80 EE subjects were included. On multivariable analyses, allergic conditions (aOR 20.1, P < 0.0001) and rings (aOR 108.3, P = 0.001) were independent predictors for PPI-r-EoE versus EE, whereas allergic conditions (aOR 4.8, P = 0.03), rings (aOR 27.5, P = 0.002) and furrows (aOR 17.1, P = 0.04) were independent predictors for PPI-nr-EoE versus EE. Esophageal rings was the only significant predictor found in PPI-nr-EoE versus PPI-r-EoE (OR 2.5, P = 0.03). Allergic conditions and esophageal rings are significantly more prevalent in PPI-r-EoE and PPI-nr-EoE compared with EE. PPI-r-EoE appears clinically similar to PPI-nr-EoE and significantly different from EE. Further studies are needed to delineate the underlying pathophysiology of PPI-r-EoE versus PPI-nr-EoE.

Overlapping Transcriptional Profile in Proton Pump Inhibitor Responsive and Nonresponsive Eosinophilic Esophagitis.

INTRODUCTION: We compared esophageal mucosal gene transcript expression in proton pump inhibitor (PPI) responsive (PPI-R) eosinophilic esophagitis (EoE), PPI nonresponsive (PPI-NR) EoE, and healthy controls. METHODS: Transcript expression in midesophagus biopsies was determined using NanoString and a custom panel of EoE-specific genes. The top upregulated and downregulated genes with ≥2-fold difference in expression and statistically significant ( P < 0.05) were identified. RESULTS: Nearly all the top upregulated (17 of 20) and downregulated (5 of 5) genes in EoE, compared with healthy controls, were shared between the PPI-R and PPI-NR groups. DISCUSSION: Esophageal mucosal transcript expressions are remarkably similar in PPI-R EoE and PPI-NR EoE compared with healthy controls.

Development of a core outcome set for therapeutic studies in eosinophilic esophagitis (COREOS).

BACKGROUND: End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. OBJECTIVE: We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. METHODS: Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. RESULTS: The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. CONCLUSIONS: This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis.

Anaphylaxis in the Radiology Suite.

Contrast media are crucial for modern medical imaging. Contrast agents are generally well tolerated. However, patients may present with adverse reactions, which can be divided into pharmacological effects or hypersensitivity reactions. We present a vignette of a patient with a past history of urticaria after radiocontrast media exposure for coronary angiography. He returns for evaluation for radiocontrast media because he needs another coronary angiography. There are no validated methods for predicting such reactions yet. Mechanisms behind adverse contrast media reactions are still not well understood. Because of unknown contrast agent, the patient was successfully pretreated with corticosteroids and an H1 antihistamine.

Engaging patient partners in state-of-the-art allergy care: Finding balance when discussing risk.

OBJECTIVE: To review risk communication in the context of shared decision making. DATA SOURCES: Articles describing risk communication, shared decision making, and cost-effective healthcare delivery. STUDY SELECTIONS: A narrative review detailing approaches to improve risk communication and shared decision making to optimize patient-centered cost-effective practice. RESULTS: Risk communication must occur on a foundation of mutual trust and can be improved by keeping risk in perspective of everyday hazards, such as using pictograms when possible, providing numeric likelihoods of risks and benefits, and discussing absolute risks. Variability in patient-perceived quality of life for allergic and nonallergic health states may affect the health and economic outcomes of many allergy therapies. Shared decision making improves patient knowledge and risk perception, engagement, and adherence. Patient decision aids can be time-consuming to develop and validate, but their use is associated with a more accurate understanding of patient-oriented outcomes. CONCLUSION: Communicating risk is complex, and validated patient decision aids using visual aids, presenting essential information, using knowledge checks, and incorporating values clarification can reduce decisional conflict and improve decisional self-efficacy.

Current Knowledge and Management of Hypersensitivity to Perioperative Drugs and Radiocontrast Media.

Perioperative anaphylaxis is an iatrogenic clinical condition, most often after anesthetic induction. Several mechanisms are implicated, including IgE- and non-IgE-mediated mechanisms. Perioperative anaphylaxis tends to be severe and has a higher mortality rate than anaphylaxis in other settings. This is partly due to factors that impair early recognition of anaphylaxis. Neuromuscular blocking agents, latex containing products, and antibiotics are the most common etiology. Chlorhexidine and dyes are increasingly culprits. The newest emerging cause is sugammadex, which is used for reversal of the effects of steroidal neuromusclar agents, such as rocuronium. Latex-induced allergy is becoming less common than in the 1980s due to primary and secondary prevention measures. Serum tryptase levels during the time of anaphylaxis and skin testing to suspected agents as an outpatient are necessary to confirm the diagnosis. Management includes epinephrine and aggressive fluid therapy. With radiocontrast media allergy, patients with a history of immediate hypersensitivity reactions to radiocontrast media should receive steroid and antihistamine premedication before re-exposure. Because IgE-mediated anaphylaxis to radiocontrast media is rare, there is a universal consensus that routinely skin testing all patients with a past reaction is not effective.

Endoscopic Features and Eosinophil Density Are Associated with Food Impaction in Adults with Esophageal Eosinophilia.

BACKGROUND AND AIMS: Food impaction has been described in both eosinophilic esophagitis and proton pump inhibitor-responsive esophageal eosinophilia. The association between endoscopic/histologic features of esophageal eosinophilia and food impaction remains unclear. We aimed to identify clinical, endoscopic, and histologic findings associated with a history of food impaction in esophageal eosinophilia. METHODS: This was a retrospective cohort study of adult esophageal eosinophilia patients at a tertiary center in 6/2005-10/2014. Only patients with ≥15 eosinophils/high-power field on mucosal biopsies were included. Demographics, comorbidities, symptoms, endoscopic/histologic findings on initial endoscopy, and history of food impaction were reviewed. Statistical analyses were performed using Fisher's exact test (univariate) and forward stepwise logistic regression (multivariate). RESULTS: 400 patients (42 ± 14 years, 61 % male) were included, with 78 (20 %) having food impaction history. On univariate analyses, rings (62 vs 42 %, p = 0.003), erosions (12 vs 5 %, p = 0.03), eosinophil density on biopsy (40 [IQR = 30-50] vs 30 [IQR = 15-50], p = 0.004), and dysphagia (88 vs 62 %, p < 0.0001) were more prevalent among patients with food impaction history, while heartburn (10 vs 33 %, p < 0.0001) and abdominal pain (1 vs 12 %, p = 0.002) were less common. On multivariate analysis, rings (OR 2.6, p = 0.002), erosions (OR 3.2, p = 0.02), and eosinophil density (ß-coefficient = 0.01, p = 0.04) remained associated with food impaction. CONCLUSIONS: Findings of rings and erosions on endoscopy and increased eosinophil density on histology were independently associated with a history of food impaction in adult esophageal eosinophilia patients. Food impaction may result from both active inflammation (erosions and increased eosinophil density) and chronic fibrostenotic changes (rings).

Desensitizations for chemotherapy and monoclonal antibodies: indications and outcomes.

Acute infusion reactions to both chemotherapeutic agents and humanized monoclonal antibodies can occur, which may limit therapeutic options for treatment of malignancies and chronic inflammatory diseases. Many of these acute infusion reactions are consistent with a type I hypersensitivity reaction, including anaphylaxis. If a patient experiences a significant acute infusion reaction, often the recommendation is to discontinue the medication and find an alternative agent. However, the "second-line" agent may be more toxic or inferior. If the reaction is likely a type I or type IV hypersensitivity reaction, one option is to undergo desensitization to the offending drug. Drug desensitization is the process of readministering a needed drug in incremental doses over hours or days until a full therapeutic dose is tolerated. This article will review the current literature on indications and outcomes for drug desensitization in the management of allergy to either chemotherapeutic agents or monoclonal antibodies.

First-trimester sex hormone binding globulin and subsequent gestational diabetes mellitus.

OBJECTIVE: We sought to examine the association between early pregnancy levels of sex hormone binding globulin and subsequent gestational diabetes mellitus, an association that has not been studied previously. STUDY DESIGN: We conducted a nested case-control study of 44 patients with gestational diabetes mellitus and 94 women with negative third-trimester screening for gestational diabetes mellitus. Sex hormone binding globulin levels were measured from serum samples that had been collected in the first trimester, and clinical data were ascertained from prospectively collected electronic medical records. RESULTS: Compared with women without gestational diabetes mellitus, first-trimester sex hormone binding globulin levels were lower among women in whom gestational diabetes mellitus subsequently developed (187 +/- 82 nmol/L vs 233 +/- 92 nmol/L, P <.01). In logistic regression analysis that was adjusted for body mass index, age, race, smoking, blood pressure, serum testosterone and estradiol levels, and gestational age at serum collection, sex hormone binding globulin levels remained independently associated with subsequent gestational diabetes mellitus. For every 50-nmol/L increase in sex hormone binding globulin, the odds of gestational diabetes mellitus fell by 31% (odds ratio, 0.69; 95% CI: 0.48, 0.99). CONCLUSION: Sex hormone binding globulin offers a potential early marker to target women who are at risk for gestational diabetes mellitus.