The Art of Immunotherapy.

Selection of a patient with rhinitis/conjunctivitis or asthma for allergy immunotherapy (AIT) requires several decisions. First, does the patient's sensitization, pattern of exposure to an allergen, and degree of exposure to that allergen reasonably suggest a causal relationship? Does the level and duration of symptoms warrant the cost and inconvenience of immunotherapy, or is the patient motivated by the disease-modifying potential of AIT? If AIT is selected, is the choice to be greater safety and convenience with sublingual immunotherapy (SLIT) tablets, but with treatment probably limited to 2 or 3 allergens, or for subcutaneous immunotherapy where multiple allergen therapy is the rule and efficacy may be somewhat greater, at least initially, or does the physician go off-label into the unknowns of liquid SLIT? Are there extracts of sufficient potency to achieve likely effective doses? How does the physician deal with large local or systemic reactions, with gaps in treatment, with pollen seasons, and the use of premedication or cautionary prescription of epinephrine autoinjectors? How can adherence to AIT be improved? These and other questions are addressed in this paper.

Allergy immunotherapy for allergic fungal respiratory diseases.

Background: Allergy immunotherapy (AIT) with fungal extracts is not as straight forward as that with other inhalants. The complexities relate to the number of airborne fungal spores, the limited data on the exposure to the spores of individual species of fungi and their clinical importance, the poor quality of the fungal allergen extracts that are available for the diagnosis and treatment, and the lack of controlled studies establishing dosing and efficacy of AIT with fungal extracts except for Alternaria. Objective: The objective was to review what is known with regard to the role of fungi in causing allergic respiratory diseases as well as the evidence that exists for the role of AIT as a treatment for these conditions. Methods: A search was conducted of PubMed, textbooks, known articles on immunotherapy with fungal extracts, and references derived from these primary sources. Results: Nine immunotherapy studies that used Alternaria or its major allergen Alt a 1 and two studies that used Cladosporium herbarum were identified. When a good quality extract was administered in adequate doses, immunotherapy with Alternaria was as effective as that with other inhalant allergens. There was a suggestion of efficacy with a specially prepared Cladosporium extract, but systemic reactions were common and limited the tolerated dose. The use of immunotherapy as an adjunct treatment for allergic fungal sinusitis is briefly reviewed, but controlled trials are lacking. Conclusion: Fungal immunotherapy should largely be limited to Alternaria alternata and perhaps C. herbarum. Under conditions of demonstrated exposure to a particular species of fungus and with symptoms that correlate with that exposure as well as availability of an apparently potent extract of that fungus to which the patient is sensitive that fungus may be considered for immunotherapy. Fungal (mold) mixes should not be used for diagnosis or therapy.

Double-Blind, Placebo-Controlled Study of E-B-FAHF-2 in Combination With Omalizumab-Facilitated Multiallergen Oral Immunotherapy.

BACKGROUND: Oral immunotherapy (OIT) is limited by adverse events, and most patients require continued treatment to maintain their increased threshold. Adjunctive treatments have been explored to increase the safety and efficacy of OIT. OBJECTIVE: This study aimed to determine the safety and efficacy of enhanced, butanol purified Food Allergy Herbal Formula-2 (E-B-FAHF-2) for inducing remission in subjects undergoing omalizumab-facilitated multiallergen OIT (multi-OIT). METHODS: In this double-blind, placebo-controlled clinical trial, subjects were randomized 1:1 to receive either E-B-FAHF-2 or placebo, starting 2 months before OIT and continuing throughout OIT. All subjects received a 4-month course of omalizumab, starting 2 months before OIT through the 2-month OIT build-up phase. After 24 months of multi-OIT (maintenance dose of 1000 mg of each allergen), desensitization and remission were assessed. The primary objective was to determine if subjects in the E-B-FAHF-2 group (EOIT) were more likely than the placebo group (OIT) to develop remission to all 3 allergens treated with multi-OIT, as defined by the absence of dose-limiting symptoms to a cumulative dose of 4444 mg of protein after discontinuing treatment for 3 months. RESULTS: Thirty-three subjects were randomized. A total of 63.6% were desensitized to 4444 mg of protein for each allergen at 26 months, and 24.2% met the primary outcome of remission at 29 months, with no difference between the treatment groups. There was good adherence (>85%) with study medications, with no difference between the treatment groups. There was no difference in reported overall adverse events between the treatment groups. CONCLUSION: Omalizumab-facilitated multifood OIT was safe and effective, and remission was achieved in about a quarter of subjects. However, outcomes were not improved by the addition of E-B-FAHF-2.

Allergen immunotherapy: progress and future outlook.

INTRODUCTION: Allergy, the immunological hypersensitivity to innocuous environmental compounds, is a global health problem. The disease triggers, allergens, are mostly proteins contained in various natural sources such as plant pollen, animal dander, dust mites, foods, fungi, and insect venoms. Allergies can manifest with a wide range of symptoms in various organs and be anything from just tedious to life-threatening. A majority of all allergy patients are self-treated with symptom-relieving medicines, while allergen immunotherapy (AIT) is the only causative treatment option. AREAS COVERED: This review will aim to give an overview of the state-of-the-art allergy management, including the use of new biologics and the application of biomarkers, and a special emphasis and discussion on current research trends in the field of AIT. EXPERT OPINION: Conventional AIT has proven effective, but the years-long treatment compromises patient compliance. Moreover, AIT is typically not offered for food allergies. Hence, there is a need for new, effective, and safe AIT methods. Novel routes of administration (e.g. oral and intralymphatic), hypoallergenic AIT products, and more effective adjuvants hold great promise. Most recently, the development of allergen-specific monoclonal antibodies for passive immunotherapy may also allow the treatment of patients currently not treated or treatable.

Combined application of dupilumab and mite allergen-specific immunotherapy in children with moderate to severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease that manifests in skin dryness, severe itching, and eczema, and can significantly impact a patient's quality of life. Current treatment regimens do not prevent the recurrence of the disease and are associated with adverse effects. Here, we report two cases of moderate-to-severe AD in children that were treated with dupilumab, a dual inhibitor of IL-4 and IL-13 signaling, in combination with mite allergen-specific immunotherapy. CASE SUMMARY: Both patients presented with the diagnosis of AD that was not adequately controlled by the conventional treatment regimen, including topical corticosteroids (TCS), topical calcineurin inhibitors, emollients, and the traditional Chinese medicine treatments. In both patients, AD-associated skin irritation impacted the quality of life, disturbed sleep patterns, and caused stress and anxiety.Patients received treatment with dupilumab and mite allergen-specific immunotherapy in addition to the baseline treatment regimen of external glucocorticoids (TCS) and oral antihistamines. Nine months after beginning of treatment, clinical symptoms, signs, medication scores, and evaluation scale scores of both children significantly improved, and the treatment was associated with an overall good tolerance. CONCLUSION: A combination of dupilumab and mite allergen-specific immunotherapy in addition to the standard anti-AD treatment improves clinical symptoms and is not associated with increased incidence of adverse effects.

Health and economic impact of subcutaneous allergen immunotherapy in patients with pollen-induced allergic rhinoconjunctivitis: real-word evidence from the Czech Republic.

Background: The prevalence of allergic rhinoconjunctivitis (AR) has been increasing over the years, and allergen immunotherapy (AIT) remains the only disease-modifying treatment. However, cost-effectiveness data remain scarce. Methods: In this single-arm, noninterventional, prospective, multicenter study, we describe the effectiveness, safety and costs of subcutaneous AIT for pollen-induced allergic rhinoconjunctivitis. Results: Of 471 new AIT users, 317 completed three courses of treatment, and symptoms improved in 96%; no serious adverse reactions were reported. The cost of symptomatic medication decreased by 49% and the cost of unscheduled specialist visits decreased by 73%. Except for AIT administration, total healthcare costs decreased by 54% compared with the baseline pollen season without AIT. Conclusion: In clinical practice, subcutaneous AIT is an effective treatment generating savings on symptomatic medication and unscheduled consultations.

Hay fever has become more frequent over the years, and allergen immunotherapy (AIT) remains the only treatment able to reduce both symptoms and the root cause of this condition. However, it is not clear whether the benefits outweigh the price of the therapy. In this study, we observed patients in the common practice and described the effectiveness, safety and costs of injected AIT for pollen-induced hay fever. Of 471 new AIT users, 317 completed three courses of treatment in 3 consecutive years. Symptoms improved in 96% of them; no serious adverse reactions were reported. The cost of symptom-relieving medication decreased by 49% and the cost of unscheduled physician visits decreased by 73%. Except for costs related to AIT administration, total healthcare costs decreased by 54% compared with the years before AIT. In clinical practice, injected AIT is an effective treatment which generates savings on other medication and unscheduled physician consultations.

Safety of subcutaneous immunotherapy with carbamylated allergoids based on data from a pharmacovigilance database.

Aims: Allergen immunotherapy aims to induce tolerance, which persists after its discontinuation, to targeted allergens. However, concern exists regarding the use of subcutaneous immunotherapy with whole extracts due to frequently reported events of anaphylactic reactions. Materials & methods: In this pharmacovigilance study, the authors assessed the safety of subcutaneous immunotherapy with the monomeric allergoid Lais-in using a database of adverse reactions documented in real-world postmarketing reports from 2010 to 2020. Results & conclusion: The results showed that more than 171,916 doses of Lais-in were administered from 2010 to 2020, resulting in five adverse drug reactions. Nonserious adverse events, including hives, eye irritation and skin reactions, were reported. These data indicate that monomeric allergoids prevent serious reactions to subcutaneous immunotherapy.

Standardized allergen extracts for allergen immunotherapy.

Nineteen U.S. allergen extracts were standardized by the U.S. Food and Drug Administration (FDA) between 1987 and 1998, including of two house-dust mites, short ragweed, cat hair and cat pelt, seven temperate and one southern grass, and six Hymenoptera venom preparations. Relevant literature was reviewed. For each allergen, a "representative" extract was established; the potency of each representative extract was determined by measurement of the total protein content (Hymenoptera venom), radial diffusion measurement of the dominant allergen (short ragweed and cat), or, if there was no dominant allergen, then by quantitative skin testing by using the ID50EAL (intradermal dilution for 50 mm sum of erythema determines the bioequivalent allergy units) method. In vitro tests were developed to allow the manufacturer to demonstrate that each lot of its extract was statistically identical, within defined limits, to the FDA reference extract. These tests included radial immunodiffusion, competitive enzyme-linked immunosorbent assay, and isoelectric focusing. The standardized extracts offer the advantage of consistent potency from lot to lot for each manufacturer and also from manufacturer to manufacturer, and assure the presence of recognized significant allergens within the extract. Therefore, standardized extracts offer improved safety and efficacy over their nonstandardized predecessors.

miRNA profiles change during grass pollen immunotherapy irrespective of clinical outcome.

Background: Subcutaneous immunotherapy (SCIT) is widely used in the treatment of allergic rhinitis (AR). This study aimed to determine the expression of 48 miRNAs in patients with AR undergoing grass pollen SCIT and investigate relations with clinical outcomes. Methodology: Expression of selected miRNAs was determined using RT-PCR in the full blood of 16 patients with AR and seven healthy controls. Results: miR-136, miR-208 and miR-190 were upregulated in the AR group. After 6 months of SCIT, significant downregulation of some proinflammatory miRNAs and upregulation of several miRNAs regulating Th1/Th2 balance were found. No differences were found between good and poor responders. Conclusion: miRNAs may play a regulatory role in SCIT, leading to tolerance induction.

Background: Subcutaneous immunotherapy is widely used in the treatment of allergic rhinitis (AR). MicroRNAs (miRNAs) are small molecules controlling gene expression. Their role in the process of immunotherapy is not yet well understood. This study aimed to investigate the expression of 48 miRNAs in patients with AR undergoing grass pollen immunotherapy and relations between miRNAs and clinical outcomes. Methodology: The expression of selected miRNAs was determined in the blood of 16 patients with AR and seven healthy people. Results: Three miRNAs were found to be overproduced in allergic patients. During immunotherapy, the production of several proinflammatory miRNAs was reduced while those responsible for allergen tolerance were produced in larger amounts. Conclusion: miRNAs may play an important role in immunotherapy, leading to better tolerance of allergens.

Mapping naso-ocular symptom scores to EQ-5D-5L utility values in Japanese cedar pollinosis.

BACKGROUND: The total naso-ocular symptom score (TSS) is widely used as an endpoint to evaluate the severity of seasonal allergic rhinitis. However, it is not a generic preference-based measure. We sought to develop an algorithm for mapping between the TSS and health utility in Japanese cedar pollinosis (JCP). We also performed a cost-utility analysis of sublingual immunotherapy (SLIT) for JCP by using this algorithm. METHODS: Patients with JCP filled out the TSS questionnaire and EQ-5D-5L simultaneously during the pollen season in 2019 and in 2020. We estimated a direct utility mapping model by regressing responses to individual TSS questions directly onto utility. The incremental cost-effectiveness ratio (ICER) of active SLIT to a placebo was determined by examining the drug expense and the estimated quality-adjusted life year (QALY) using a dataset from a double-blind placebo-controlled clinical trial. RESULTS: A total of 238 records were included for analysis. The estimated utility decreased with increasing severity of rhinitis. Patients with comorbid asthma showed lower utility. A negative and significant correlation was seen between the TSS and utility in both 2019 and 2020. The estimated equations were: Y(utility) = -0.0161∗X(TSS) + 1.005 in non-asthmatic JCP patients. The ICER of active SLIT to the placebo was estimated to be 4,049,720 and 6,011,218 JPY/QALY in the first and second year, respectively. CONCLUSIONS: It is possible to reasonably predict utility from the total naso-ocular symptom score by using regression models. In the estimated algorithm, pre-seasonal SLIT for JCP is cost-effective.

Safety and Effectiveness of a Single Multiallergen Subcutaneous Immunotherapy in Polyallergic Patients.

BACKGROUND: As the number of allergic sensitizations increases the severity of allergic respiratory diseases worsens. Multiple monoallergen immunotherapy can be accompanied by poor treatment adherence and high costs, single multiallergen immunotherapy needs to prove efficacy whilst maintaining a good safety profile. METHODS: Observational, retrospective, multicenter study using a 2-pollen single undiluted multiallergen subcutaneous immunotherapy (SCIT) in routine clinical practice in Spain. Patients with rhinoconjunctivitis, with/without controlled asthma, sensitized to grass, olive, Parietaria, Cupressus, plane tree and/or Salsola pollen were included. Primary and secondary clinical efficacy endpoints were quality of life (mini Rhinitis Quality of Life Questionnaire (miniRQLQ)) and visual analogue scale (VAS) respectively. All adverse events were documented. RESULTS: Ten centers included 97 patients, median age 32 years. SCIT treatment included combinations of grass mix with olive, Parietaria, Cupressus, plane tree or Salsola or olive with Parietaria, Cupressus or Salsola. The mean duration of SCIT was 1.8 years with a high treatment adherence (73%). Significant improvement in quality of life, nasal and ocular symptoms, activity limitations and practical problems (p< 0.0001) and other symptoms (p= 0.024) was observed. Most patients did not develop asthma-like symptoms and a significant improvement of all allergic symptom severity was perceived. VAS showed a significant improvement in rhinoconjunctivitis and asthma by patients and physicians. Twenty-nine patients experienced adverse reactions, 25 had local and 6 had systemic reactions. CONCLUSIONS: Single undiluted multiallergen SCIT treatment of two different pollens is efficacious and safe in both children and adults, showing that it is a suitable option for the treatment of polyallergic patients.

Japanese cedar and cypress pollinosis updated: New allergens, cross-reactivity, and treatment.

Pollen from many tree species in the Cupressaceae family is a well-known cause of seasonal allergic diseases worldwide. Japanese cedar pollinosis and Japanese cypress pollinosis, which are caused by pollen from Japanese cedar (Cryptomeria japonica) and Japanese cypress (Chamaecyparis obtusa), respectively, are the most prevalent seasonal allergic diseases in Japan. Recently, the novel major Japanese cypress allergen Cha o 3 and the homologous Japanese cedar allergen Cry j cellulase were identified, and it was shown, for the first time, that cellulase in plants is allergenic. Although the allergenic components of pollen from both species exhibit high amino acid sequence identity, their pollinosis responded differently to allergen-specific immunotherapy (ASIT) using a standardized extract of Japanese cedar pollen. Pharmacotherapy and ASIT for Japanese cedar and cypress pollinosis have advanced considerably in recent years. In particular, Japanese cedar ASIT has entered a new phase, primarily in response to the generation of updated efficacy data and the development of new formulations. In this review, we focus on both Japanese cypress and cedar pollinosis, and discuss the latest findings, newly identified causative allergens, and new treatments. To manage pollinosis symptoms during spring effectively, ASIT for both Japanese cedar and Japanese cypress pollen is considered necessary.

Allergen fragrance molecules: a potential relief for COVID-19.

BACKGROUND: The latest coronavirus SARS-CoV-2, discovered in China and rapidly spread Worldwide. COVID-19 affected millions of people and killed hundreds of thousands worldwide. There are many ongoing studies investigating drug(s) suitable for preventing and/or treating this pandemic; however, there are no specific drugs or vaccines available to treat or prevent SARS-CoV-2 as of today. METHODS: Fifty-eight fragrance materials, which are classified as allergen fragrance molecules, were selected and used in this study. Docking simulations were carried out using four functional proteins; the Covid19 Main Protase (MPro), Receptor binding domain (RBD) of spike protein, Nucleocapsid, and host Bromodomain protein (BRD2), as target macromolecules. Three different software, AutoDock, AutoDock Vina (Vina), and Molegro Virtual Docker (MVD), running a total of four different docking protocol with optimized energy functions were used. Results were compared with the five molecules reported in the literature as potential drugs against COVID-19. Virtual screening was carried out using Vina, molecules satisfying our cut-off (- 6.5 kcal/mol) binding affinity was confirmed by MVD. Selected molecules were analyzed using the flexible docking protocol of Vina and AutoDock default settings. RESULTS: Ten out of 58 allergen fragrance molecules were selected for further docking studies. MPro and BRD2 are potential targets for the tested allergen fragrance molecules, while RBD and Nucleocapsid showed weak binding energies. According to AutoDock results, three molecules, Benzyl Cinnamate, Dihydroambrettolide, and Galaxolide, had good binding affinities to BRD2. While Dihydroambrettolide and Galaxolide showed the potential to bind to MPro, Sclareol and Vertofix had the best calculated binding affinities to this target. When the flexible docking results analyzed, all the molecules tested had better calculated binding affinities as expected. Benzyl Benzoate and Benzyl Salicylate showed good binding affinities to BRD2. In the case of MPro, Sclareol had the lowest binding affinity among all the tested allergen fragrance molecules. CONCLUSION: Allergen fragrance molecules are readily available, cost-efficient, and shown to be safe for human use. Results showed that several of these molecules had comparable binding affinities as the potential drug molecules reported in the literature to target proteins. Thus, these allergen molecules at correct doses could have significant health benefits.

Patch testing 101, part 1: performing the test.

Understanding the basics of patch testing is essential to caring for patients with contact dermatitis. Several screening or standard series are available, and additional allergens or series may be necessary based on the patient's history. A delayed reading should be performed 72 to 144 hours after patch placement. Certain oral medications, phototherapy, or topical products may interfere with patch test results.

Long-term efficacy of injected allergen immunotherapy for treatment of grass pollen allergy in elderly patients with allergic rhinitis.

Background: The effect of prolonged allergen immunotherapy is still insufficiently known, especially in elderly patients. Objective: The effect after a 3-year course of injected allergen-specific immunotherapy (AIT) for grass pollen allergy in elderly patients with allergic rhinitis was observed. Methods: Thirty-eight elderly patients (mean ± standard deviation, 66.2 ± 2.7 years old) who received preseasonal injected AIT or placebo for grass pollen allergy were monitored for 3 years and compared with a placebo group. The combined symptom medication score (CSMS), serum level of immunoglobulin G4 (IgG4) to phleum pratense 5 (Phl p5) and quality of life were assessed immediately after AIT and 3 years later. Results: After AIT, the CSMS was significantly decreased from 2.15 (range, 1.27-3.00) to 1.13 (range, 0.79-1.36) (p = 0.03) and remained lower (1.41 ± 0.72 versus 2.41 ± 1.11) than that in the placebo group during the 3 years after AIT. Serum-specific IgG4 against increased during the course of AIT and remained at a high level during further observation. Quality of life, based on the Rhinoconjunctivitis Quality of Life Questionnaire, was significantly decreased in the patients who received AIT from 1.51 (95% confidence interval [CI], 1.21-1.84) to 1.01 (95% CI, 0.93-1.87) (p < 0.05) and was decreased to 0.97-1.26 (95% CI, 0.88-1.82) during the 3 years after discontinuation of AIT. Conclusion: A prolonged positive effect after AIT for grass pollen allergy was observed in elderly patients with allergic rhinitis. Further trials are needed to confirm this effect.Clinical trial MC56871/12, www.clinicaltrials.gov.

The Honeybee Venom Major Allergen Api m 10 (Icarapin) and Its Role in Diagnostics and Treatment of Hymenoptera Venom Allergy.

PURPOSE OF REVIEW: In Hymenoptera venom allergy, the research focus has moved from whole venoms to individual allergenic molecules. Api m 10 (icarapin) has been described as a major allergen of honeybee venom (HBV) with potentially high relevance for diagnostics and therapy of venom allergy. Here, we review recent studies on Api m 10 characteristics as well as its role in component-resolved diagnostics and potential implications for venom-specific immunotherapy (VIT). RECENT FINDINGS: Api m 10 is a major allergen of low abundance in HBV. It is an obviously unstable protein of unknown function that exhibits homologs in other insect species. Despite its low abundance in HBV, 35 to 72% of HBV-allergic patients show relevant sensitization to this allergen. Api m 10 is a marker allergen for HBV sensitization, which in many cases can help to identify primary sensitization to HBV and, hence, to discriminate between genuine sensitization and cross-reactivity. Moreover, Api m 10 might support personalized risk stratification in VIT, as dominant sensitization to Api m 10 has been identified as risk factor for treatment failure. This might be of particular importance since Api m 10 is strongly underrepresented in some therapeutic preparations commonly used for VIT. Although the role of Api m 10 in HBV allergy and tolerance induction during VIT is not fully understood, it certainly is a useful tool to unravel primary sensitization and individual sensitization profiles in component-resolved diagnostics (CRD). Moreover, a potential of Api m 10 to contribute to personalized treatment strategies in HBV allergy is emerging.

Comparison of Six Different Allergen Extracts for Subcutaneous Specific Immunotherapy in Children: An Open-Labelled, Prospective, Controlled Observational Trial.

BACKGROUND: Numerous products are available for subcutaneous (SCIT) and sublingual allergen-specific immunotherapy, but there are no information about the direct comparability regarding efficacy, safety, and tolerability of the different extracts. AIMS: The aim of this open-labelled, prospective, controlled observational trial was to test the feasibility of a comparison of different products for SCIT in children. METHODS: Pediatrician practices recruited patients with a confirmed diagnosis of a seasonal allergic rhinoconjunctivitis (AR) with or without asthma and an allergic sensitization against grass pollen allergen. Every patient was offered SCIT with one out of six allergen extracts: ALK SQ Depot, ALK Avanz, Allergovit, Depigoid, Purethal, Pollinex Quattro. Scores for symptoms and medications were calculated and the difference between treatment years and baseline were recorded. RESULTS: In total, 284 were recruited and 255 children (89.8%; mean age 10.4, SD 3.54 years; 65% males) participated in this trial. Overall, 49,649 patient days were recorded in the electronic database (mean 183.2 days/patient). There was no significant difference in the AR and asthma symptom score or the medication score between the six different SCIT preparations. Similarly, no differences were observed in terms of safety and tolerability. CONCLUSION: The comparison of different SCIT products using an online tool is feasible. Based on our preliminary data, all extracts indicated efficacy; however, larger groups would be necessary to demonstrate superiority or non-inferiority of one specific SCIT product.

Providing cost-effective care for food allergy.

OBJECTIVE: To review the cost-effectiveness of food allergy management strategies. DATA SOURCES AND STUDY SELECTIONS: A narrative review and synthesis of literature identified using a PubMed search of relevant articles describing cost-effectiveness evaluations of food allergy management. RESULTS: Screening at-risk infants for peanut allergy carries risk of overdiagnosis and is not cost-effective. Evidence suggests that cost-effective care could be better optimized by minimizing delay in oral food challenges for eligible patients, clarifying the role of precautionary allergen labeling, incorporating patient-preference sensitive care in activation of emergency medical services for resolved allergic reactions, and considering value-based pricing and school-supply models for epinephrine. Finally, the annual value-based cost (willingness to pay [WTP] $100,000/quality-adjusted life years [QALY]) of peanut immunotherapy has been estimated to be between $1568 and $6568 for epicutaneous immunotherapy (EPIT) and between $1235 and $5235 for probiotic with peanut oil immunotherapy (POIT), with each therapy showing more favorable cost-effectiveness with greater improvements in health utility, particularly if sustained unresponsiveness can be achieved. CONCLUSION: Many aspects of food allergy management are not cost-effective, and recent evaluations suggest a greater role for incorporating patient and family preferences into guideline-based and traditionally reflexive management decisions. Caregiver understanding of food allergy screening tradeoffs is critical, given that screening children before allergen exposure has significant costs and results in overdiagnosis, especially when oral food challenges are omitted from diagnostic algorithms. Cost-effectiveness analysis can help to identify important decision levers in patient management across a wide range of topics. Further research is needed to better understand health state utilities of specific patient populations.

Tolerability and positive efficacy results after subcutaneous immunotherapy with Parietaria judaica depot extract.

AIM: To evaluate tolerability and efficacy of Parietaria judaica subcutaneous immunotherapy on patients with allergic rhinoconjunctivitis. PATIENTS & METHODS: 51 patients were assigned to build-up scheme (six increasing doses) of P. judaica depot native extract, plus three maintenance monthly administrations. RESULTS: Out of 470 administered doses, only 3.8% elicited systemic reactions (1.5% nonspecific and 2.3% grade I). Concerning the exploratory efficacy parameters: cutaneous reactivity at the final visit versus baseline was significantly decreased; specific titers of IgG and IgG4 increased significantly and patients showed a significant decrease in the rhinitis symptoms score. CONCLUSION: P. judaica subcutaneous immunotherapy (Allergovac® depot ROXALL Medicina España S.A., Zamudio, Spain) with an abbreviated up-dosing scheme showed an adequate safety and tolerability profile and induced preliminary efficacy changes.