Indonesia-Based Study of the Clinical and Cost-Saving Benefits of Subcutaneous Allergen Immunotherapy for Children with Allergic Rhinitis in Private Practice.

BACKGROUND: Until now, the cost of allergy treatment in the insured public health care system and the non-insured self-financing private health care system in Indonesia has not been well documented and published, as well as the cost of allergy treatment with subcutaneous immunotherapy. OBJECTIVE: To evaluate the clinical and cost benefits of allergic rhinitis treatment in children with subcutaneous immunotherapy in a non-insured self-financing private health care system. METHODS: A retrospective cohort study conducted from 2015 until 2020 that compared the clinical improvement and health care costs over 18 months in newly diagnosed AR children who received SCIT versus matched AR control subjects who did not receive SCIT, with each group consisting of 1098 subjects. RESULTS: A decrease in sp-HDM-IgE level (kU/mL) from 20.5 + 8.75 kU/mL to 12.1 + 3.07 kU/mL was observed in the SCIT group. To reduce the symptom score of allergic rhinitis by 1.0 with SCIT, it costs IDR 21,753,062.7 per child, and for non-SCIT, it costs IDR 104,147,878.0 per child. Meanwhile, to reduce the medication score (MS) by 1.0 with SCIT, it costs IDR 17,024,138.8, while with non-SCIT, it costs IDR 104,147,878.0. Meanwhile, to lower combination symptoms and medication score (CSMS) by 1.0, with SCIT, it costs IDR 9,550,126.6, while with non-SCIT, it costs IDR 52,073,938.9. CONCLUSIONS: In conclusion, this first Indonesia-based study demonstrates substantial health care cost savings associated with SCIT for children with AR in an uninsured private health care system and provides strong evidence for the clinical benefits and cost-savings benefits of AR treatment in children.

Aqueous intradermal low-dose house dust mite immunotherapy in tropical settings: a valid cost-effective approach for developing nations?

INTRODUCTION: Aqueous allergen injections, an effective and century-old technique, is considered a second-line approach in daily clinical practice. Inconveniences still surround conventional subcutaneous immunotherapy (SCIT) administration, such as a need for frequent injections, prolonged up-dosing schedules, elevated costs, and the unlikely possibility of a systemic reaction. The intradermal immunotherapy route (IDR) might favorably impact many of the aforementioned issues (Table 1). House dust mite (HDM) allergens are the main perennial sensitizers in the tropics, and as such, are solely employed in immunotherapy treatments. METHODS: We carried out a year-long real-life study in 25 perennial allergic rhinitis children, symptomatic on exposure to house dust, employing an intradermal low-dose allergen mix consisting of 50 ng of Dermatophagoides pteronyssinus/Dermatophagoides farinae and 120 ng of Blomia tropicalis, under a unique cost-wise protocol. Basal symptoms/signs and face Visual Analog Scale (fVAS) scores were recorded for 2 weeks and later compared with those registered throughout the 1-year treatment. Serum-specific IgG4 and IL-10 levels were employed in the assessment of the immune responses. RESULTS: Symptoms/signs and fVAS scores were significantly reduced from days 42 and 49, respectively, and remained so until treatment completion. Increases in specific IgG4's and IL-10 levels reflected significant immune responses. Injections were well tolerated and families reported improved health status (quality of life, QoL). CONCLUSIONS: A unique cost-effective immunotherapy alternative for deprived allergic communities in tropical settings is depicted; further research is needed.

Geographical and socioeconomic differences in compliance with and access to allergen immunotherapy in Denmark: A nationwide registry-based study - 1998-2016.

BACKGROUND: Allergen immunotherapy (AIT) is a cost-effective treatment option in moderate-severe allergic rhino-conjunctivitis. Inequality in access to AIT and variation in compliance related to socioeconomic status or geographical location have not been described previously. OBJECTIVE: The aim of the study was to evaluate access to grass pollen AIT at various educational attainment levels in the five regions of Denmark. Furthermore, grass pollen AIT treatment compliance was evaluated with respect to age, educational attainment and geographical area. METHODS: The unique civil registration number of every citizen in Denmark was combined with the nationwide Danish National Health Service Prescription Database and Statistics Denmark Database to extract age, gender, residence and educational attainment of every citizen who collected prescribed AIT medication from 1998 to 2016. Then, compliance and use of AIT were calculated with respect to age, geographical location and educational attainment. RESULTS: The use of subcutaneous AIT (SCIT) was significantly higher in the Capital Region; this difference was less predominant for sublingual AIT (SLIT). People who were educated only to primary school or vocational training levels were less frequent users of AIT. Compliance was especially low in the Capital Region and among people educated only to primary school level. In the age groups, compliance was similar, apart from SLIT users aged 0-9, for whom compliance was higher. CONCLUSION: This nationwide study finds that SLIT has the potential to reduce inequality in access to AIT. A focus intervention is needed to facilitate access to and compliance with AIT in groups with lower socioeconomic status.

Biologic Agents for the Treatment of Anaphylaxis.

Several biologic therapies and new devices are emerging as potential preventive treatment of anaphylaxis. However, adrenaline (epinephrine) is still the first-line treatment of any type of anaphylaxis. Biologic drugs, such as omalizumab, although not US Food and Drug Administration approved for anaphylaxis, have been used as therapeutic adjuvants in the preventive treatment of anaphylaxis, but cost-effectiveness should be considered individually.

Biologics and Allergy Immunotherapy in the Treatment of Allergic Diseases.

Allergic diseases represent some of the most chronic and costly chronic conditions. Medical management may require long-term pharmacotherapy, which is often associated with poor adherence. Although medications provide symptomatic control, they do not modify the allergic disease. Patients may prefer disease-modifying treatments that provide lasting benefits after discontinuation. To date, allergy immunotherapy is the only proved disease modification therapy associated with lasting benefits after discontinuation. However, allergy immunotherapy safety and efficacy has only been established in allergic rhinitis, mild to moderate asthma, and some patients with atopic dermatitis.

Health and Economic Outcomes of Home Maintenance Allergen Immunotherapy in Select Patients with High Health Literacy during the COVID-19 Pandemic: A Cost-Effectiveness Analysis During Exceptional Times.

BACKGROUND: Allergen immunotherapy (AIT) is safe and effective but is typically administered under strict clinic observation to mitigate the risk of a systemic reaction to immunotherapy (SRIT). However, in the setting of the global coronavirus disease 2019 pandemic, alternative care models should be explored. OBJECTIVE: To evaluate the cost-effectiveness of home immunotherapy self-administration (HITSA) in a highly idealized circumstance for provision of maintenance AIT in a shelter-in-place or other scenarios of unforeseen reduction in nonessential medical services. METHODS: Markov modeling was used to compare in-office clinic AIT in selected patients using cohort analysis and microsimulation from the societal and health care perspectives. RESULTS: Assuming similar SRIT rates, HITSA was found to be a cost-effective option with an incremental cost-effectiveness ratio of $44,554/quality-adjusted life-year when considering both incremental epinephrine autoinjector costs and coronavirus disease 2019 risks. Excluding epinephrine autoinjector costs, HISTA dominated other options. However, outside of pandemic considerations, HITSA was not cost-effective (incremental cost-effectiveness ratio, $198,877,286) at annual epinephrine autoinjector costs above $287. As the incremental HITSA SRIT rate increased above 15%, clinic AIT was the most cost-effective strategy. Excluding both pandemic risks and risk of motor vehicle accident fatality from round-trip clinic transit, clinic AIT dominated other strategies. Clinic AIT was the more cost-effective option at very high fatality relative risk for HITSA or at very low annual risk of contracting coronavirus disease 2019. CONCLUSIONS: Under idealized assumptions HITSA can be a safe and cost-effective option during a global pandemic in appropriately selected patients provided home rates of SRIT remain stable.

Mechanisms of Subcutaneous and Sublingual Aeroallergen Immunotherapy: What Is New?

Allergen immunotherapy (AIT) is considered to be the only treatment option with the promise of healing and induction of long-lasting allergen tolerance, persisting even after discontinuation of therapy. Despite a more than 100-year-long history, still only a minority of patients are being treated with AIT. Substantial developments took place in the last decade to overcome problems in standardization, efficacy, safety, high costs, long duration of treatment; and new guidelines have also been implemented. Major advancements in the understanding of AIT mechanisms with the focus on recent findings of subcutaneous and sublingual AIT have been summarized.

The Cost-Effectiveness of Allergen Immunotherapy Compared with Pharmacotherapy for Treatment of Allergic Rhinitis and Asthma.

This article evaluates the cost-effectiveness of allergy immunotherapy (AIT) in the treatment of allergic rhinitis, asthma, and other allergic conditions. An extensive search of the PubMed and Medline databases (up to December 2018) was conducted. There is strong evidence in the collective literature, which included individual studies and systematic reviews, that AIT is cost-effective in the management of allergic rhinitis and asthma as compared with standard drug treatment alone. The magnitude of AIT's cost-effectiveness is likely underestimated because most of the studies considered during-treatment costs and not the long-term benefits or preventive or prophylactic effects of AIT.

Allergen Immunotherapy and Atopic Dermatitis: the Good, the Bad, and the Unknown.

PURPOSE OF REVIEW: In light of the recent advancements in atopic dermatitis treatment, this review aims to summarize the utility and efficacy of allergy immunotherapy in atopic dermatitis patients. We examine its mechanism, pathophysiology, cost-efficacy, and current guidelines for clinical practice. RECENT FINDINGS: The literature supports the use of allergy immunotherapy in atopic conditions such as allergic rhinitis and asthma but insufficient evidence exists to suggest its efficacy in atopic dermatitis. The use of allergy immunotherapy has been shown to provide long-term cost savings in both the USA and the European Union in certain populations but differences in prescribing patterns and manufacturing make it difficult to study its impact on a larger, generalizable scale. Conflicting meta-analyses data and conclusions highlight the need for better, higher quality research to better understand allergy immunotherapy utility in atopic dermatitis.

Sulfonamide desensitization in solid organ transplant recipients: A protocol-driven approach during the index transplant hospitalization.

Trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line agent for Pneumocystis jiroveci pneumonia (PJP) prophylaxis for solid organ transplant (SOT) recipients because of its efficacy for this indication, extended antimicrobial coverage, and favorable cost. Reported sulfonamide allergy is not uncommon and often results in TMP-SMX avoidance. Desensitization offers an efficacious and cost-effective alternative to TMP-SMX avoidance. Herein, we reviewed our experience with desensitization during the index transplant hospitalization among 52 SOT recipients with history of a non-anaphylactic sulfonamide allergy. Of those enrolled in the desensitization protocol, 92% (48/52) completed the protocol, with nearly 80% (41/52) still on TMP-SMX at 3 months without adverse reaction. Eleven patients discontinued TMP-SMX (7 for allergic reactions and 4 for non-allergic reasons) and switched to pentamidine. A cost savings of $575 per desensitization was calculated based on annual wholesale drug prices, for a total savings of $23 575. Additionally, the protocol did not delay discharge in any patient nor was it associated with any severe allergic reactions. These findings suggest TMP-SMX desensitization is safe and effective in SOT recipients with a history of non-anaphylactic, non-life-threatening sulfonamide hypersensitivity.

The cost-effectiveness of requiring universal vs contextual self-injectable epinephrine autoinjector for allergen immunotherapy.

BACKGROUND: Aeroallergen immunotherapy (AIT) is a safe and effective disease-modifying treatment associated with rare therapy-associated fatality. Significant practice variation surrounds universal or contextual prescription of self-injectable epinephrine (SIE) for patients receiving AIT. OBJECTIVE: To characterize the cost-effectiveness of a universal vs contextual SIE requirement for patients receiving AIT. METHODS: An economic evaluation using cohort and microsimulation was performed from both the societal and health care sector perspectives for patients undergoing AIT, assessing a universal requirement to fill SIE prescriptions at the outset of therapy compared with requiring this only after a systemic reaction to immunotherapy (SRIT). RESULTS: A universal SIE requirement for AIT is not cost-effective, with the incremental cost-effectiveness ratio for this strategy estimated at $669,327,730 per quality-adjusted life-year (QALY). In the microsimulation (n = 10,000), the mean (SD) costs of a universal approach exceeded that of a more context-specific strategy where SIE was only prescribed for patients after an initial SRIT ($19,653.36 [$4296.66] vs $16,232.14 [$5204.32]), and given the effects on rates of AIT discontinuation, the universal approach was less effective (mean [SD], 25.555 [2.285] QALYs) compared with a contextualized approach (mean [SD], 25.579 [2.345] QALYs). Universal SIE prescription could be cost-effective if it provided a 1000 times protection against AIT fatality at a value-based cost of $24, and the annual AIT fatality rates unrealistically exceed 2.6 per 10,000 patients. CONCLUSION: In a simulation of potential SIE-prescribing strategies for patients receiving AIT, a universal approach to an epinephrine autoinjector requirement was not cost-effective when compared with an approach in which an SIE is prescribed only to patients with prior SRIT.

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.

Estimation of Health and Economic Benefits of Commercial Peanut Immunotherapy Products: A Cost-effectiveness Analysis.

Importance: Commercial epicutaneous peanut immunotherapy (EPIT) and peanut oral immunotherapy (POIT) may offer significant quality-of-life improvements for patients with peanut allergy, but the cost-effectiveness of commercial peanut immunotherapies is uncharacterized. Objective: To evaluate critical inputs associated with the cost-effectiveness of EPIT and POIT from a societal perspective. Design, Setting, and Participants: Economic evaluation in which microsimulations with Markov modeling were performed evaluating virtual children aged 4 years over an 80-year time horizon. The base-case costs included a caregiver-reported willingness to pay of $3839 annually for safe and effective food allergy treatment. Estimates of predictive biomarkers or oral challenges were incorporated after the first year of therapy with additional analyses of immunotherapy risk reduction of anaphylaxis and probability of sustained unresponsiveness (SU) to peanut after 4 years. Exposures: Children received EPIT, POIT, or no immunotherapy treatment (n = 10 000 per treatment strategy). Main Outcomes and Measures: Rates of therapy-associated adverse reactions and quality-of-life improvements associated with changes in eliciting or tolerated peanut doses were modeled along with quality-adjusted life-years (QALYs), anaphylaxis, therapy-associated anaphylaxis, and fatalities. Results: In the base-case analysis without SU to peanut, the EPIT strategy cost less than POIT (mean [SD] cost, $154 662 [$46 716] vs $163 524 [$56 800]) and had fewer total episodes of anaphylaxis (mean [SD], 1.33 [1.55] vs 3.83 [5.02] episodes) and fewer episodes of therapy-associated anaphylaxis (mean [SD], 0.62 [1.30] vs 3.10 [4.94] episodes) but had lower QALY accumulation (mean [SD], 26.932 [2.241] vs 26.945 [2.320] QALYs). The incremental cost-effectiveness ratio was $216 061 for EPIT and $255 431 for POIT. Models were sensitive to therapy cost, SU rates, health state utility, and risk reduction of anaphylaxis. With health state utility sensitivity analyses, the ceiling value-based cost (willingness-to-pay threshold $100 000/QALY) was between $1568 and $6568 for EPIT and between $1235 and $5235 for POIT. If high rates of SU to peanut can be achieved in longer-term models, EPIT and POIT could produce savings in terms of both cost and QALY. Conclusions and Relevance: In this simulated analysis, findings showed that EPIT and POIT may be cost-effective under some assumptions. Further research is needed to understand the degree of health state utility improvement associated with each therapy, degree of protection against anaphylaxis, and rates of SU.

Outcomes, complications, and economic impact of ABO-incompatible living kidney transplantation: A single-center Japanese cohort study.

ABO-incompatible kidney transplantation (ABO-ILKT) has been reported to have a higher rate of early complications and higher medical costs than ABO-compatible kidney transplantation (ABO-CLKT). We aimed to compare the clinical outcomes, complications, and medical costs between ABO-ILKTs and ABO-CLKTs at 2 years post-transplantation. We included 65 ABO-ILKTs and 94 ABO-CLKTs in this retrospective analysis. The patient survival, graft survival, rejection incidence, and graft function were similar between ABO-CLKT and ABO-ILKT. The hospitalization costs for ABO-CLKT and ABO-ILKT were 26 544 ± 4168 USD and 34 906 ± 18 732 USD, respectively (P = 0.0001). Total 2-year medical costs were 77 117 ± 15 609 USD and 85 325 ± 33 997 USD for ABO-CLKT and ABO-ILKT, respectively, indicating that the medical costs of ABO-ILKT recipients were non-significantly higher than those of ABO-CLKT recipients at 2 years post-transplantation (P = 0.0866). ABO-ILKT and ABO-CLKT recipients showed similar infectious adverse events and complications. In conclusion, medical cost at 2 years post-transplantation, including transplant hospitalization cost, and the frequency of early complications were not significantly higher in the ABO-ILKT group than in the ABO-CLKT group. ABO-ILKT is an acceptable treatment for patients with ESRD and is comparable to ABO-CLKT not only in terms of outcomes but also in terms of medical cost.

Adherence to Subcutaneous Allergen Immunotherapy in Southeast Turkey: A Real-Life Study.

BACKGROUND Subcutaneous immunotherapy (SCIT) in allergic rhinitis (AR) and asthma is a very effective treatment, but adherence is still a serious problem. Studies addressing real-life adherence to SCIT are rare in the literature. The aim of this study was to evaluate the adherence to SCIT in AR and asthma. MATERIAL AND METHODS The medical records of patients prescribed SCIT for treatment of AR and/or asthma were evaluated. Patients who continued the SCIT treatment as prescribed were defined as adherent, patients who stopped the treatment before the recommended period were defined as nonpersistent, and those who never started the treatment were defined as primary poor adherence. Age, gender, residence, type of SCIT, comorbidities, occupation, income, and adverse reactions were evaluated between these groups. RESULTS Ninety-five patients prescribed SCIT for the treatment of AR and/or asthma formed our cohort (female/male: 51/44). The mean (SD) age and duration of SCIT were 32.2±10.0 (range, 17-63) years, 14.4±12.7 (1.0-58.5) months, respectively. Sixty-two (65.3%) patients were adherent, (28.4%) patients were nonpersistent, and 6 (6.3%) patients were primary poor adherent. Nineteen (21.4%) patients had local adverse reactions and one (1.1%) had anaphylaxis. There were no differences between groups for age, gender, residence, type of SCIT, comorbidities, income, or occupation. The most frequent reason of nonpersistence was the cost of treatment. CONCLUSIONS Our study found that adherence to SCIT is low in a real-life setting in southeast Turkey, similar to most previous adherence studies.

Does evidence support the use of cat allergen immunotherapy?

PURPOSE OF REVIEW: Cat allergy can manifest as allergic rhinitis, conjunctivitis and/or asthma. With widespread cat ownership and exposure, cat allergy has emerged as a major cause of morbidity. Cat allergen immunotherapy is a potential disease modifying treatment for patients with cat allergy. We examine evidence on the effectiveness, cost-effectiveness and safety of cat allergen immunotherapy and consider the clinical contexts in which it should be prescribed. RECENT FINDINGS: The European Association of Allergy and Clinical Immunology systematic reviews on allergic rhinitis and asthma along with the accompanying guidelines on allergic rhinitis were used as primary sources of evidence. Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) are most common routes of administration for allergen immunotherapy (AIT). A limited number of high-quality studies related to cat dander have shown mixed results in improvements in ocular and nasal symptoms, asthma symptoms, peak expiratory flow rate and medication use scores with subcutaneous immunotherapy. Two studies examining cat dander and cat-related allergy response with sublingual immunotherapy have shown mixed results in terms of symptomatic response. One randomized trial examining intralymphatic immunotherapy has shown a positive symptom response and a favourable safety profile. Although studies have reported mixed results regarding safety of SCIT, adverse events have been reported more commonly with SCIT than SLIT. SUMMARY: There is a limited body of high-quality evidence on the effectiveness and safety of cat AIT and no high-quality data on its cost-effectiveness. The available evidence on effectiveness is mixed based on studying a limited array of immunological, physiological and patient-reported outcome measures. Based on this evidence and extrapolating on the wider evidence base in AIT, it is likely that some patients may benefit from this modality of treatment, particularly those with moderate-to-severe disease who are inadequately controlled on allergen avoidance measures and pharmacotherapy and those who are monosensitized to Felix Domesticus 1. Further evidence is, however, required from larger trials before more definitive advice can be offered.

Health economic analysis of allergen immunotherapy for the management of allergic rhinitis, asthma, food allergy and venom allergy: A systematic overview.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is developing guidelines for allergen immunotherapy (AIT) for the management of allergic rhinitis, allergic asthma, IgE-mediated food allergy and venom allergy. To inform the development of clinical recommendations, we undertook systematic reviews to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT for these conditions. This study focusses on synthesizing data and gaps in the evidence on the cost-effectiveness of AIT for these conditions. METHODS: We produced summaries of evidence in each domain, and then, synthesized findings on health economic data identified from four recent systematic reviews on allergic rhinitis, asthma, food allergy and venom allergy, respectively. The quality of these studies was independently assessed using the Critical Appraisal Skills Programme tool for health economic evaluations. RESULTS: Twenty-three studies satisfied our inclusion criteria. Of these, 19 studies investigated the cost-effectiveness of AIT in allergic rhinitis, of which seven were based on data from randomized controlled trials with economic evaluations conducted from a health system perspective. This body of evidence suggested that sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) would be considered cost-effective using the (English) National Institute for Health and Clinical Excellence (NICE) cost-effectiveness threshold of £20 000/quality-adjusted life year (QALY). However, the quality of the studies and the general lack of attention to characterizing uncertainty and handling missing data should be taken into account when interpreting these results. For asthma, there were three eligible studies, all of which had significant methodological limitations; these suggested that SLIT, when used in patients with both asthma and allergic rhinitis, may be cost-effective with an incremental cost-effectiveness ratio (ICER) of £10 726 per QALY. We found one economic modelling study for venom allergy which, despite being based largely on expert opinion and plausible assumptions, suggested that AIT for bee and wasp venom allergy is only likely to be cost-effective for very high-risk groups who may be exposed to multiple exposures to venom/year (eg bee keepers). We found no eligible studies investigating the cost-effectiveness of AIT for food allergy. CONCLUSIONS: Overall, the evidence to support the cost-effectiveness of AIT is limited and of low methodological quality, but suggests that AIT may be cost-effective for people with allergic rhinitis with or without asthma and in high-risk subgroups for venom allergy. We were unable to draw any conclusions on the cost-effectiveness of AIT for food allergy.