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

BACKGROUND: Omalizumab is an anti-IgE therapy newly approved by the Food and Drug Administration for allergen agnostic treatment of single or multiple food allergies in patients aged 1 year or older. OBJECTIVE: Evaluate the cost-effectiveness of omalizumab as a food allergy treatment. METHODS: We evaluated health and economic outcomes in Markov cohorts of simulated food allergic infants randomized to receive omalizumab using a 15-year 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. We included family-level analysis to incorporate a broad perspective for health utility change, given treatment effects likely benefit all parties at home (eg, caregivers, siblings), not just the patient, representing the sum of changes in all such persons. Supplemental analyses explored lower omalizumab cost and home initiation. We performed deterministic and probabilistic sensitivity analyses. RESULTS: In the family-level cohort analysis, omalizumab exceeded cost-effectiveness thresholds ($185,183/quality-adjusted life-years [QALY]). In a comparison of the omalizumab strategy (OMA) with the non-omalizumab strategy, the cost of OMA exceeded the non-omalizumab strategy ($315,020 vs $136,609) with greater incremental effectiveness (12.668 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 (willingness to pay, $100,000/QALY) at a health state utility (HSU) improvement of 0.265. The value-based cost of OMA ranged from $14,166 to $23,791 when it was considered at the individual and family-unit levels. Requiring OMA administration in the clinic was not cost-effective (incremental cost-effectiveness ratio, $260,239). CONCLUSIONS: In the base case and at current pricing, omalizumab is not cost-effective, but it could be at a lower retail price or when use creates large health utility shifts in the family and patient.

The Need for Required Stock Epinephrine in All Schools: A Work Group Report of the AAAAI Adverse Reactions to Foods Committee.

Epinephrine is the first line of treatment for anaphylaxis that can occur outside a medical setting in community environments such as schools. Patients with diagnosed IgE-mediated food allergy at risk of anaphylaxis are prescribed self-injectable epinephrine and given an individualized anaphylaxis action plan. As students, such patients/families provide their school with completed medication forms, a copy of their anaphylaxis plan, and additional student-specific epinephrine. However, students approved to self-carry prescribed self-injectable epinephrine may forget to do so or have other reasons for lacking prescribed epinephrine such as familial inability to fill the prescription due to cost or other access barriers. Undiagnosed students lacking prescribed epinephrine may also experience anaphylaxis at school. The presence of non-student-specific school stock epinephrine allows school nurses and other staff the ability to treat anaphylaxis onsite while awaiting Emergency Medical Services. Notably, not all states legally mandate K-12 schools to stock epinephrine. In states with laws only voluntarily allowing schools to stock epinephrine, it provides the ability to opt-out. Herein, we present a comprehensive review of barriers to school stock epinephrine, related improvement strategies, and workgroup recommendations supporting the need for mandated stock epinephrine in all schools in every state. Proposed solutions include ensuring legal immunity from liability for prescribers; advocacy for legislation to stabilize cost of self-injectable epinephrine; educational initiatives to schools promoting merits and safety of epinephrine and related anaphylaxis training; and partnerships between patient advocacy groups, medical and nursing organizations, public health departments and other health professionals to promote laws and district policies addressing need for stock epinephrine and school nurses to train and supervise school staff.

Epinephrine Auto-Injector Prescription and Use: A Retrospective Analysis and Clinical Risk Assessment of Adult Patients Sensitized to Lipid Transfer Protein.

Lipid transfer proteins (LTPs) are widely widespread plant food allergens which represents the main cause of food allergy in adults living in the Mediterranean basin. The purpose of this study was to investigate in LTP patients the actual use of prescribed epinephrine auto-injector and appropriateness of its prescription. In addition, we investigated in these patients: (1) occurrence of new food reaction in the following three years after to diagnosis; (2) need and number of access to emergency services; (3) presence of possible predictive factors to further food reactions. One-hundred sixty-five adult patients sensitized to LTPs have been included. During follow-up, we recorded 68 further reactions, most of them (77.9%) characterized by local symptoms; rarely the patients required an emergency-department visits (16.1%) and only one patient (1.7%) used the epinephrine auto-injector. The patients with a previous history of anaphylaxis at baseline turned back to access to emergency services also during the follow-up (p = 0.006). The majority of patients with recorded systemic reactions (p = 0.004) and treated in an emergency room (p = 0.028) did not have any co-factor-enhanced at diagnosis. We noted an association between platanus pollen sensitization and severity of further reactions during the follow-up (p = 0.026). Epinephrine auto-injector were prescribed to 108/165 patients (65.5%) with an over-prescription rate of 25%. The unforeseeable clinical presentation of LTP allergic reactions and the eventual role played by the cofactor make necessary schedule a follow-up to monitor the patients over time and to assess the actual use of epinephrine auto injectors prescribed.

Cost-Effectiveness of Food Allergy Interventions in Children: A Systematic Review of Economic Evaluations.

OBJECTIVES: To identify published economic evaluations of interventions aimed at preventing, diagnosing, or treating food allergies in children. METHODS: We examined economic evaluations published from 2000 to 2019. Data analyzed included: food allergy type, study population/setting, intervention/comparator, and economic evaluation details. Quality assessment used reporting and economic modeling checklists. Two reviewers simultaneously undertook article screening, data extraction, and quality assessment. RESULTS: 17 studies were included: 8 peanut allergy (PA) studies, 8 cow's milk allergy (CMA) studies, and 1 egg allergy (EA) study. All PA studies reported incremental costs per quality-adjusted life-year gained for diagnostic strategies, management pathways for peanut exposure, and immunotherapies. Immunotherapies rendered inconsistent cost-effectiveness results. CMA studies reported costs per symptom-free day or probability of developing CMA tolerance. Cost-effectiveness of extensively hydrolyzed casein formula for CMA treatment was consistently demonstrated. Early introduction of cooked egg in first year of life dominated all EA prevention strategies. Quality assessment showed average noncompliance for 3.5 items/study (range 0-11) for modeling methods and 3.4 items/study (range 0-8) for reporting quality. Key quality concerns included limited justification for model choice, evidence base for model parameters, source of utility values, and representation of uncertainty. CONCLUSION: Recent cost-effectiveness literature of interventions in PA, CMA, and EA is limited and diverse. Interventions for diagnosis and treatment of CMA and prevention of EA were generally cost-effective; however, results for PA were variable and dependent on effectiveness and utility values used. There is a need to expand economic evaluation of interventions for childhood food allergy and to improve methods and reporting.

A Cost-Effectiveness Analysis of Epinephrine Autoinjector Risk Stratification for Patients with Food Allergy-One Epinephrine Autoinjector or Two?

BACKGROUND: Food-allergic patients are routinely prescribed 2 epinephrine autoinjectors (EAIs). The cost-effectiveness of this strategy is unknown. OBJECTIVE: To evaluate the cost-effectiveness of routinely prescribing all patients 2 EAI devices versus a risk-stratified approach (2 EAIs prescribed only for patients with a risk factor). METHODS: Markov models compared universal versus risk-stratified approaches on the basis of either a previous medical history of anaphylaxis (PMH-ana) or anaphylaxis requiring multiple epinephrine doses (multi-epi). Cohorts of children with peanut allergy were evaluated over an 80-year time horizon from both US and UK societal and health care perspectives. Models assumed prescribing a second EAI provided a baseline 10-fold risk reduction versus anaphylaxis-related fatality and hospitalization. Cost-effectiveness threshold was $100,000/quality-adjusted life-year (QALY). RESULTS: From a US perspective, universal prescription of 2 EAIs to all patients with peanut allergy was not cost-effective in the base case versus risk stratification by PMH-ana. Universal prescription of 2 EAIs was associated with an incremental cost of $10,696,036/QALY versus the PMH-ana strategy, and $17,514,558/QALY versus the multi-epi strategy. However, the universal strategy became cost-effective versus a multi-epi strategy when single EAI costs were less than $80, second epinephrine dose requirements more than 25.5%, anaphylaxis hospitalization costs more than $18,453, annual anaphylaxis risk more than 76.5%, or anaphylaxis hospitalization rate more than 74.9%. From a UK perspective, universally prescribing 2 EAIs was also not cost-effective (incremental cost of $4,132,440/QALY vs PMH-ana and $6,208,227/QALY vs multi-epi) at single device costs more than $18. CONCLUSIONS: At current EAI prices and low rates of needing 2 devices, limiting the second EAIs to patients with PMH-ana is more cost-effective than routinely prescribing 2 EAIs to all patients (particularly in resource-constrained settings).

Allergen risk assessment: Food intake levels of the general population represent those of food allergic patients.

Unintentional intake of allergens through food products poses a daily risk for allergic patients. Models estimating the risk of reactions mostly use intake data from general population surveys. Our study evaluates the comparability of food intake levels in the general population to those in the food allergic population. Data were collected by a 24-h recall method on 2 non-consecutive days in 38 cow's milk and/or hen's egg and 35 peanut and/or tree nut allergic adult patients. All products were assigned to food groups previously developed for allergen risk assessment. Food intake distributions from the allergic populations and a matched sample from the Dutch National Food Consumption Survey were compared, and risk assessments were performed. Food intake data was obtained for 92% of the food groups. Comparison of the intake showed no statistically significant differences between either of the two allergic populations and the general population. Consequently, only small variations in estimated risks were found, that would not result in different risk management decisions. In conclusion, food intake data from the general population can be used for food allergen risk assessment and will not lead to a relevant under- or overestimation of the risk for the food allergic population.

Cost-Effectiveness of Stock Epinephrine Autoinjectors on Commercial Aircraft.

BACKGROUND: In-flight food-allergic reactions are rare events, but given increasing reports, grass-root advocates have lobbied to replace aircraft emergency kit epinephrine ampules with autoinjectors. OBJECTIVE: To evaluate the cost-effectiveness of stock epinephrine on commercial aircraft. METHODS: We conducted a Markov model with microsimulation of food-allergic individuals over an 80-year time horizon to evaluate the cost-effectiveness of supplementing airline medical kits with epinephrine autoinjectors (eg, providing autoinjector twin-packs in addition to the epinephrine ampule in the medical kit), versus not doing so, using a per-plane annual value-based cost ceiling of $338 (the value-based ceiling for school stock epinephrine). We assumed that autoinjector availability reduced fatality risk by 10%. RESULTS: Equipping all commercial aircraft with autoinjectors cost $2,470,422/year ($0.08/passenger-at-risk), from a societal perspective and when distributed over all at-risk travelers. Over the model horizon, the supplemental autoinjector strategy cost $32,329.29 (standard deviation [SD], $4024.32) versus $32,326.70 (SD $4024.29), produced 26.8917 quality-adjusted life-years (QALYs) (SD, 2.9720) versus 26.8915 (SD, 2.9725), with a lower fatality rate (0.00012; SD, 0.01095 vs 0.00015; SD, 0.1225) versus the ampule-only strategy. The incremental cost-effectiveness ratio of supplemental airline epinephrine autoinjectors was $10,766/QALY in the base-case analysis. The supplemental model remained cost-effective at a willingness to pay threshold of $100,000/QALY if it produced a minimum 1.4% annual food allergy fatality risk reduction, and dominated if it lowered diversion risk or event-related medical care costs-per-event by 10%, respectively. CONCLUSIONS: Under base-case scenarios, an airline supplemental stock epinephrine model is cost-effective, with a high value-based cost-ceiling and low annual cost per passenger-at-risk of $0.08.

Gluten Vehicle and Placebo for Non-Celiac Gluten Sensitivity Assessment.

Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by gastrointestinal and extraintestinal manifestations triggered after gluten ingestion in the absence of celiac disease and wheat allergy. Because of the lack of biomarkers for NCGS diagnosis, the cornerstone for its assessment is a single- or double-blind placebo-controlled (DBPC) gluten challenge. However, there are some non-standardized points in the diagnostic approach proposed by the experts. This complicate comparisons among the results published by different research groups. The gluten vehicle and placebo must be indistinguishable from each other, which entails sensory and technological evaluations of the designed gluten vehicle and placebo products. At the moment, there is no standardized method for the preparation of the gluten vehicle and placebo for carrying out DBPC gluten challenges for NCGS assessment. This review focuses on the challenges that researchers have to face, either for the development of an accepted gluten vehicle and placebo or for identifying NCGS cases on the basis of DBPC gluten challenges.

Patient Carrying Time, Confidence, and Training with Epinephrine Autoinjectors: The RACE Survey.

BACKGROUND: Limited real-world data exist regarding patient carrying compliance and confidence in using different types of epinephrine autoinjectors (EAIs). OBJECTIVE: To perform a Real-world Assessment of Patients' Carrying Time and Confidence with Epinephrine Autoinjector Devices (RACE survey). METHODS: This was a noninterventional survey of patients (≥7 years) who filled 1 or more prescription for Auvi-Q or EpiPen between January 2013 and January 2014. Outcomes included proportion of patients carrying their EAI all the time in the last 7 days (primary), EAI use confidence (secondary), and EAI training experience (secondary). Multivariate regression analyses controlled for significant differences in demographic and clinical characteristics between EAI groups. RESULTS: The survey included 2,000 participants (Auvi-Q, N = 1,000 [children, n = 597; adults, n = 403]; EpiPen, N = 1,000 [children, n = 105; adults, n = 895]). After adjusting for confounding factors, we found that Auvi-Q respondents were more likely to carry their device all the time in the last 7 days versus EpiPen respondents (adjusted odds ratio [aOR], 1.91; 95% CI, 1.49-2.45; P < .001); similar trends were observed in adults and children (P < .001 both). Adults in the Auvi-Q group were more likely to feel "very confident" about correctly using their EAI (aOR, 2.02) and someone else correctly using their EAI (aOR, 2.25) versus the EpiPen group (P < .001 both). Compared with EpiPen respondents, Auvi-Q respondents were more likely to feel that EAI instructions were "very clear" (aOR, 3.10) and more likely to find the prescription pack trainer helpful (aOR, 2.29; P < .01 both). CONCLUSIONS: This study suggests significant real-world differences in patients' carrying time, confidence in use, and training experiences between Auvi-Q and EpiPen users.

Barriers to the Administration of Epinephrine in Schools.

BACKGROUND: Anaphylaxis is a serious and growing concern in the school setting as the prevalence of food allergies and food-induced severe allergic reactions continues to increase. METHODS: A cross-sectional, web-based survey was conducted regarding anaphylactic events that occurred during the 2014-2015 school year. Eligible schools were enrolled in the EPIPEN4SCHOOLS® program (Mylan Specialty L.P., Canonsburg, PA), which provides free epinephrine auto-injectors to qualifying US schools. Participating schools completed a 29-item survey on anaphylactic event occurrence and treatment, epinephrine stock, school policies regarding anaphylaxis, school staff training, and school nursing coverage. RESULTS: Responses were provided by 12,275 schools. Epinephrine was administered on school property for 63.7% of reported anaphylactic events (1272/1998). In 38.5% (235/610) of events for which epinephrine was not used, antihistamines were cited as the reason. Only 59.4% of schools cited epinephrine as their standard first-line therapy for anaphylaxis. School nurses were most likely to be trained in anaphylaxis recognition and permitted to administer epinephrine; however, just 53.6% of schools had a full-time nurse on staff. CONCLUSIONS: Process-related barriers to the appropriate use of epinephrine go beyond access to medication. Widespread staff training and review of school policies are needed to ensure that anaphylaxis is appropriately managed in schools.

Food-Allergic Adolescents at Risk for Anaphylaxis: A Randomized Controlled Study of Supervised Injection to Improve Comfort with Epinephrine Self-Injection.

BACKGROUND: Epinephrine self-injection is a key element in the management of food allergy, yet many adolescents report that they may not be able to use the autoinjector when needed. We hypothesized that supervised self-injection with an empty syringe would increase adolescents' comfort with self-injection. OBJECTIVE: The objective of this study was to examine the effect of supervised self-injection on self- and parent-reported comfort and anxiety during and after clinic visits in a food allergy center. METHODS: Sixty adolescent/parent pairs were randomized to self-injection versus control (education only). The predefined primary outcome was a self-reported comfort level with the injection before versus after the intervention on a Likert scale with scores of 1 (Not at all comfortable) to 10 (Extremely comfortable). The primary outcome was evaluated via within-group and between-group analyses. Secondary outcomes included adolescent and parent reports before versus after the injection, and changes in quality of life (QoL) and anxiety a month later. RESULTS: Self-injection was associated with a significant immediate increase in comfort levels (primary outcome; within-group comparison: mean scores: 6.93 preintervention vs 8.37 postintervention, P < .01; between-group ANOVA: 8.37 vs 6.69, P < .01) and with significant improvements in all other predefined (secondary) measures. On follow-up, QoL improved in 52% of intervention patients as compared with 25% of controls; similar differences were observed for anxiety. Those differences were not statistically significant. CONCLUSIONS: A self-injection (with an empty syringe) procedure in a clinic setting improves adolescents' and parents' comfort level with self-injecting. It may translate into substantial clinical benefits should self-injection be needed.

Epinephrine entrepreneur.

A Minnesota allergist continues his quest to build a better--and cheaper--drug injection device for people with severe food allergies.

Food allergy prevalence and management at an overnight summer camp.

BACKGROUND: In recent years, increased awareness of food allergy management has focused on the school setting. A lack of awareness and relevant literature prompted evaluation of the camp experience. OBJECTIVE: To characterize the prevalence of food allergies among children attending an overnight summer camp and to evaluate the knowledge and comfort of camp personnel before and after a training session. METHODS: The database for the 2014 season at Flying Horse Farms was reviewed for information pertaining to food allergies and provision of epinephrine and treatment plans. Camp personnel completed surveys regarding food allergy knowledge and comfort. Surveys were redistributed 30 days after the training session. RESULTS: Among 445 campers, 15% reported at least one food allergy, with 8.5% reporting allergy to 1 of the top 8 food allergens. Only 32% of campers with food allergy supplied an epinephrine autoinjector, and 0% provided written treatment plans. Before training, 84% of personnel desired additional information about food allergies. Knowledge of food allergies among personnel was high at baseline but increased after training in regard to epinephrine use for anaphylaxis and postepinephrine management. Staffers who reported feeling very comfortable caring for campers with food allergy increased from 16% to 46% after the training session; comfort in treating a food allergy emergency increased from 2% to 29%. CONCLUSION: Management of food allergies at overnight summer camps warrants similar education and preparation strategies as those implemented in schools. Camp personnel should receive annual training regarding food allergies and anaphylaxis.

The compliance and burden of treatment with the epinephrine auto-injector in food-allergic adolescents.

BACKGROUND: Food-allergic patients at high risk of potential fatal anaphylaxis should carry an epinephrine auto-injector (EAI) at all times. This treatment may be perceived as burdensome and this may affect compliance and health-related quality of life (HRQL). The aims of the study were (1) to determine the burden of treatment (BoT) of an EAI, (2) to examine the relationship between this burden and compliance, and (3) to analyze which factors contribute to the BoT of the EAI as perceived by food-allergic adolescents and their parents. METHODS: Dutch food-allergic adolescents prescribed an EAI, and their parents completed a questionnaire package (n = 55). Relationships between BoT and HRQL, illness severity and perception, and anxiety measures were investigated. RESULTS: Food-allergic adolescents and their parents were (extremely) positive about the EAI (54.5%; 72.7%, respectively) (=low BoT). The BoT measure showed a significantly greater burden in food-allergic adolescents prescribed an EAI who reported not carrying the EAI at all times than adolescents who reported they did. The BoT scores of both adolescents and their parents were not associated with HRQL, illness severity and perception, or trait anxiety. CONCLUSIONS: The majority of food-allergic adolescents and their parents were positive about the EAI (=low BoT). However, the BoT was significantly associated with self-reported compliance with carrying the EAI. The BoT was higher in food-allergic adolescents prescribed an EAI who reported not carrying the EAI at all times. The BoT measure seems to be a useful tool to study compliance with carrying an EAI. The BoT of an EAI is not associated with HRQL. The BoT measures a distinct concept related to compliance behavior.

Factors impacting parental burden in food-allergic children.

AIM: This study aims to determine factors impacting the parental burden in immunoglobulin E (IgE)-mediated food-allergic children (FAC), focusing on attitudes towards adrenaline autoinjectors (AAIs). METHODS: Questionnaires were sent to parents of diagnosed IgE-mediated FAC attending follow-up allergy clinic appointments at two Sydney hospitals in May-September 2013. The questionnaires ascertained parental attitudes, confidence and knowledge regarding AAIs and included the validated, Food Allergy Quality of Life-Parental Burden (FAQL-PB) questionnaire. RESULTS: The response rate was 68%. Of FAC, 62% were male aged 1-17 years (median 6.0). There was a high proportion of children with multiple food allergies (52% allergic to >2 foods), coexistant eczema (85%) and asthma (54%). Sixty-three per cent reported a past history of anaphylaxis and 42% reported reactions in the last 6 months. AAI had been prescribed for 84%. FAC with a history of anaphylaxis were more likely to have had an AAI prescribed (P < 0.0001). There was no difference in FAQL-PB mean scores with age or AAI prescription status. The PB score was greater if the parent had administered the AAI (P = 0.02) and where the child was allergic to >2 foods (P < 0.0001).The Ninety per cent of parents reported that the AAI increased or did not change the child's quality of life, the family or FACs freedom. Three per cent of parents whose FAC children were prescribed an AAI reported increased stress related to AAI prescription. CONCLUSION: Severity of food allergy, number of food allergens and past anaphylaxis rather than prescription of an AAI appear to be major influences on parental burden.

[Discriminant function analysis in the assessment of laboratory test data in the correction of traditional therapy for mild icteric form of viral hepatitis B in children with food allergy].

The purpose of this investigation was to define the efficiency of inclusion of antihistamines (suprastin or tavegil), enzyme drugs (pancreatin or mesim forte) and their combinations into therapy for a mild icteric form of acute viral hepatitis B (VHB) in children with food allergy (FA). Among the examinees, there were 61 children with FA who had experienced a mild icteric form of VHB and who received traditional therapy at the age of 3-14 years. Of them, 36 children were additionally given antihistamines (n = 7), enzyme drugs (n = 20), and their combination (n = 9). About half the children (47.54%) were boys. Blood samples were biochemically tested in children for bilirubin and enzymes 1, 3, 6, 9, and 12 months after their hospital discharge. The similar laboratory tests were carried out in 20 healthy children--a comparison (control) group. Analysis of discriminant functions stated the high efficiency of inclusion of enzyme drugs, or antihistamines in particular, or their combinations with enzyme drugs, that considerably reduce the time it takes to normalize the complexes of the indices of a blood biochemical test for bilirubin and enzymes.