Cost effectiveness of omalizumab for severe asthma in Colombia.

BACKGROUND: Omalizumab is a humanized monoclonal antibody that specifically binds to free human immunoglobulin E. The introduction of this drug raises concerns about economic impact in scenarios with constrained. This study aimed to estimate the cost utility of omalizumab in adults with severe asthma uncontrolled in Colombia. METHODS: We used a Markov state-transition model to estimate the cost and QALYs associated with omalizumab compared to standard of care; from a third payer perspective over a lifetime horizon. This model used local costs while utilities were derived from international literature. Cost and transition probabilities were obtained from a mixture of Colombian-specific and internationally published data. RESULTS: The mean incremental cost of omalizumab versus standard of care is US$3 481. The mean incremental benefit of omalizumab versus standard of care 0.094 QALY. The incremental expected cost per unit of benefit is estimated at US$36846 per QALY. There is only a probability of 0.032 that Omalizumab is more cost-effective than standard of care at a threshold of US$5180 per QALY. CONCLUSION: Omalizumab is not cost-effective in adults with severe asthma uncontrolled in Colombia. If the cost of Omalizumab is reduced by 83%, this treatment would be cost-effective in our country. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.

Healthcare costs and resources utilization in children with difficult-to-control asthma treated with biologic therapies: A population-based cohort study.

INTRODUCTION: Asthma is one of the most common diseases in children, with a variable range of severity. In recent years, treatment for severe asthma has been largely improved by the availability of targeted biologic therapies. Nevertheless, studies reporting real-world data and cost-effectiveness analyses are lacking. The aim of this study was to evaluate, on a population-based cohort of children with asthma, the impact of the treatment with biologics on healthcare service utilization and associated costs. METHODS: Data were retrieved from Healthcare Utilization database of Lombardy region (Italy). A cohort of 46 asthmatic children aged 6-11 in treatment with dupilumab, mepolizumab or omalizumab was identified during 2017-2021. We compared healthcare resources use between the year before ("baseline period") and the year after the treatment initiation ("follow-up period"). Average 1-year healthcare costs were also calculated. RESULTS: Comparing the baseline with the follow-up period, the number of patients with at least one exacerbation-related hospitalization and ER access decreased by 75.0% and 85.7%, respectively. The use of biologic agents, namely omalizumab, mepolizumab and dupilumab, significantly reduced oral corticosteroids (OCS), short-acting ß2-agonists and the association inhaled corticosteroids/long-acting ß2-agonists use. ER admissions for non-respiratory causes were also significantly reduced, while discontinuation rate was low (6.5%). The overall costs increased, due to the costs of the biologic agents, but the hospital admission-related costs due to respiratory causes reduced significantly. CONCLUSIONS: Our real-world investigation suggests that biologic agents reduced hospital admissions for respiratory causes and use of anti-asthmatic drugs, including OCS. However, long-term healthcare sustainability still needs more in-depth assessments.

Cost-effectiveness analysis of dupilumab versus omalizumab, mepolizumab, and benralizumab added to the standard of care in adults with severe asthma in Colombia.

BACKGROUND: Cost-effectiveness studies evaluate health technologies and help choose treatments. The current study compared dupilumab to omalizumab, mepolizumab, and benralizumab in Colombian adults with severe uncontrolled type 2 asthma. METHODS: Over a 5-year period, a Markov model was utilized to assess the costs of biological treatments and management of exacerbations, comparing various doses of exacerbations, comparing various doses of dupilumab, omalizumab, mepolizumab, and benralizumab as add-on treatments. It included a 5% annual discount rate per local HTA, and set willingness-to-pay at three times GDP per capita per quality-adjusted life year (QALY) in Colombia. RESULTS: Dupilumab (200 mg) exhibited greater QALYs and reduced overall costs compared to mepolizumab (100 mg), benralizumab (30 mg), and omalizumab (450 mg and 600 mg), with the incremental cost-effectiveness ratio (ICER) per QALYgained being -$5.429, -$6.269, -$196.567 and -$991.007, respectively. Dupilumab had greater QALYs and costs versus omalizumab 300 mg (ICERof $200.653 per QALY, above the willingness-to-pay threshold of 3 × GDP per capita). Sensitivity analyses were consistent with base case results. CONCLUSIONS: Dupilumab 200 mg was strongly dominant versus omalizumab 450 mg and 600 mg, mepolizumab 100 mg, and benralizumab 30 mg; however, cost-effectiveness was not demonstrated versus omalizumab 300 mg. These results could assist healthcare professionals in choosing an appropriate biologic for treating severe type 2 asthma.

Combined analytical assays for the characterization of drugs binding to human IgE: Applicability to omalizumab-bearing biosimilar candidates assessment.

Analytical and functional comparison is key for substantiating the level of convergence (essential sameness) or divergence between versions or variants of a given biological medicine. Accordingly, an overlapping biological activity between products meant to be equal probably reflects a highly similar structure and anticipates a comparable pharmacodynamic behavior. We developed an orthogonal approach to compare the human IgE binding features of different lots and versions of Xolair® (omalizumab), an anti-human IgE monoclonal antibody. The IgE binding affinity and kinetics were measured by surface plasmon resonance. Ability to prevent mast cell activity was assessed in vitro and in vivo in mast cell-based models. The variability of monoclonal antibodies with identical amino acid sequences produced either in Chinese hamster ovarian cells or in human HEK293 cells, was compared. Monoclonal antibodies from the two sources exhibited slightly different human IgE binding and neutralizing features. A known variant exhibiting a three amino acid replacement in the Fab region had lower IgE binding affinity than the original omalizumab. The lower binding affinity translated into reduced IgE neutralizing capacity and, in turn, a difference in the ability to prevent mast cell activation in vitro and in vivo. The proposed set of analytical and functional assays was sensitive enough to detect Fab-linked differences between anti-IgE antibody versions exhibiting an identical aminoacid sequence. In addition to add value to the comparative assessment of biosimilar candidates bearing omalizumab, these methods can aid pre-assessments of new anti-IgE agents that aim to improve therapeutic performance.

Impact of benralizumab on asthma exacerbation-related medical healthcare resource utilization and medical costs: results from the ZEPHYR 2 study.

BACKGROUND AND AIM: Benralizumab is a biologic add-on treatment for severe eosinophilic asthma that can reduce the rate of asthma exacerbations, but data on the associated medical utilization are scarce. This retrospective study evaluated the economic value of benralizumab by analyzing healthcare resource utilization (HRU) and medical costs in a large patient population in the US. METHODS: Insurance claims data (11/2016-6/2020) were analyzed. A pre-post design was used to compare asthma exacerbation rates, medical HRU and medical costs in the 12 months pre vs. post index (day after benralizumab initiation). Patients were aged ≥12 years, with ≥2 records of benralizumab and ≥2 asthma exacerbations pre index, and constituted non-mutually exclusive cohorts: biologic-naïve, biologic-experienced (switched from omalizumab or mepolizumab to benralizumab), or with extended follow-up (18 or 24 months). RESULTS: In all cohorts (mean age 51-53 years; 67-70% female; biologic-naïve, N = 1,292; biologic-experienced, N = 349; 18-month follow-up, N = 419; 24-month follow-up, N = 156), benralizumab treatment reduced the rate of asthma exacerbation by 53-68% (p < .001). In the biologic-naïve cohort, inpatient admissions decreased by 58%, emergency department visits by 54%, and outpatient visits by 58% post index (all p < .001), with similar reductions in exacerbation-related medical HRU in other cohorts. Exacerbation-related mean total medical costs decreased by 51% in the biologic-naïve cohort ($4691 pre-index, $2289 post-index), with cost differences ranging from 16% to 64% across other cohorts (prior omalizumab: $2686 to $1600; prior mepolizumab: $5990 to $5008; 18-month: $3636 to $1667; 24-month: $4014 to $1449; all p < .001). Medical HRU and cost reductions were durable, decreasing by 64% in year 1 and 66% in year 2 in the 24 month follow-up cohort. CONCLUSION: Patients treated with benralizumab with prior exacerbations experienced reductions in asthma exacerbations and exacerbation-related medical HRU and medical costs regardless of prior biologic use, with the benefits observed for up to 24 months after treatment initiation.

Benralizumab is a biologic approved as an add-on treatment for severe eosinophilic asthma. Previous real-world studies and clinical trials have shown that benralizumab can reduce the rate of asthma exacerbations and systemic corticosteroid use. However, there is little information on the economic value of benralizumab in real-world patient populations. This study showed that patients with severe asthma in the United States had lower rates of asthma exacerbations after starting treatment with benralizumab. The patients also had fewer asthma exacerbation-related hospitalizations, emergency department visits, and outpatient visits as well as lower medical costs related to asthma exacerbations compared with before the treatment. These benefits were observed in patients who had never taken and those who had been previously treated with biologic therapies, and for up to 24 months after starting benralizumab treatment. These results show that the clinical value of benralizumab translates into reduced medical utilization for patients with severe asthma.

Real-world patient-level cost-effectiveness analysis of omalizumab in patients with severe allergic asthma treated in four major medical centers in Turkey.

AIMS: To evaluate the cost-effectiveness of standard-of-care treatment (SoC) to SoC in combination with omalizumab (OML + Soc) in patients with severe asthma using real-world prospective clinical data from four major medical centers in Turkey. MATERIALS AND METHODS: Between February 2018 and November 2019, a total of 206 patients with severe asthma, including 126 of whom were in the OML + SoC group and 80 in the SoC group, were followed for 12 months to evaluate their asthma status and quality of life. Cost data for this patient-level economic evaluation were sourced from the MEDULA database of the hospitals and expressed in Turkish Lira (₺). Efficacy data were obtained by means of Turkish versions of the Asthma Control Test for asthma status, the 5-level EQ-5D-5L version (EQ-5D-5L), and the Asthma Quality of Life Scale for quality of life. A Markov model with 2-week cycles was specified, comparing costs and treatment effects of SoC vs. OML + SoC over a lifetime from the Turkish payer perspective. RESULTS: Per-patient costs were ₺23,607.08 in the SoC arm and ₺425,329.81 in the OML + Soc arm, for a difference of ₺401,722.74. Life years (LY) and quality-adjusted life years (QALY) were 13.60 and 10.08, respectively, in the SoC group; and 21.26 and 13.35, respectively, in the OML + SoC group, for differences of 7.66 LYs and 3.27 QALYs. This yielded an incremental cost-effectiveness ratio of an additional ₺52,427.04 to gain 1 LY and an incremental cost-utility ratio of an incremental ₺122,675.57 to gain 1 QALY; the latter being below the ₺156,948 willingness-to-pay threshold for Turkey referenced by WHO. One-way and multivariate sensitivity analyses confirmed the base-case results. CONCLUSION: Whereas most economic evaluations are based on aggregate data, this independent cost-effectiveness analysis using prospective real-world patient-level data suggests that omalizumab in combination with standard of care is cost-effective for severe asthma from the Turkish public payer perspective.

What is the context? Severe asthma, a subset of difficult-to-treat asthma, refers to asthma that cannot be controlled despite adherence to optimized maximal therapy and treatment of contributing factors, or asthma that worsens when high-dose therapy is reduced.Omalizumab is the first biologic therapy approved for the treatment of allergic asthma. Its main role is to prevent the release of various inflammation factors that cause severe asthma episodes.Cost-effectiveness analysis is an economic method of determining how much more a new and better treatment costs relative to the current treatment in terms of how many life years (LY) and how many quality-adjusted life years (QALY) are gained with the new treatment. Cost-effectiveness results tell us how much more money is needed over the cost of the current treatment to achieve one additional LY, regardless of the quality of life, or one additional LY with good quality of life.No cost-effectiveness data obtained from actual clinical patient data are available for Turkey. What is new? Our study found that the addition of omalizumab to the current standard of care for severe asthma increases costs but also increases life years and quality-adjusted life years. The additional cost was less than what the World Health Organization assumes is reasonable for Turkey.This study used actual clinical patient data and noted that asthma patients in the omalizumab group used fewer health services, had a better clinical course, had a better quality of life, and lived longer with their disease under control.What is the impact? In severe asthmatic patients, adding omalizumab to standard-of-care, while more costly, yields better outcomes and is therefore cost-effective.The cost-effectiveness estimates fall within the margins of being cost-responsible. The Turkish public payer should strongly consider making omalizumab available to all eligible patients. This will enable working-age patients to work, and contribute to their families, while also strengthening the Turkish economy.

Cost-effectiveness of omalizumab for the treatment of severe pediatric allergic asthma-Results of a real-life study in Spain.

BACKGROUND: Severe pediatric allergic asthma (SPAA) induces a huge economic burden in terms of direct, indirect, and intangible costs. The use of omalizumab for the treatment of these patients has produced a significant improvement in several clinical outcomes, but at the same time, the cost for the management of the disease has also increased. The aim of this report was to evaluate whether the use of omalizumab is cost-effective. METHODS: A sample of 426 children with SPAA from the ANCHORS (Asthma iN CHildren: Omalizumab in Real-life in Spain) study was used to calculate the incremental cost-effectiveness ratio (ICER) for the avoidance of moderate-to-severe exacerbations (MSE) and also for the improvement in childhood Asthma Control Test (c-ACT) or the Asthma Control Questionnaire (ACQ5). We retrospectively collected data on health encounters and drug consumption before and up to 6 years after the beginning of the treatment with omalizumab. RESULTS: The ICER per avoided MSE was €2107 after 1 year, and it consistently decreased to €656 in those followed up to 6 years. Similarly, the ICER for the minimally important difference in control tests showed a decrease from €2059 to €380 per each 0.5 points of improvement in ACQ5 and from €3141 to €2322 per each 3 points improvement in c-ACT, at years 1 and 6, respectively. CONCLUSION: The use of OMZ is a cost-effective option for most children with uncontrolled SPAA, especially those who have frequent exacerbations; the costs are progressively reduced in successive years of treatment.

Incremental net monetary benefit of biologic therapies in moderate to severe asthma: a systematic review and meta-analysis of economic evaluation studies.

OBJECTIVES: This meta-analysis was conducted to quantitatively pool the incremental net benefit (INB) of using biologic therapies as an add-on treatment to standard therapy in patients with moderate to severe asthma. METHODS: We performed a comprehensive search in several databases published until April 2022. Studies were included if they were cost-effectiveness analyses reporting cost per quality-adjusted life-year or life-year on any biologic therapies as an add-on treatment for moderate to severe asthma in patients of all ages. Various monetary units were converted to purchasing power parity, adjusted to 2021 US dollars. The INBs were pooled across studies using a random-effects model, stratified by country income level (high-income countries (HICs) and low- and middle-income countries (LMICs)) and perspectives (health care or payer perspective (HCPP) and societal perspective (SP)) and age group (>12 years and 6-11 years). Heterogeneity was assessed using the I2 statistic. RESULTS: A total of 32 comparisons from 25 studies were included. Pooled INB indicated that the use of omalizumab as an add-on treatment to standard therapy in those aged >12 years was not cost-effective in HICs from the HCPP (n = 8, INB, -6,341 (95% CI, -$25,000 to $12,210), I2=86.18%) and SP (n = 5, -$14,000 (-$170,000 to $140,000), I2=75.64%). A similar finding was observed in those aged 6-11 years from the HCPP in LMICs (n = 2, -$45,000 (-$73,000 to $17,000), I2=00.00%). Subgroup analyses provided no explanations of the potential sources of heterogeneity. CONCLUSION: The use of biologic therapies in moderate to severe asthma is not cost-effective compared to standard treatment alone.

Incorporating Dynamic Pricing in Cost-Effectiveness Analysis: Are Known Unknowns Valuable?

BACKGROUND: Current practice in health technology assessment (HTA) of pharmaceuticals conducts cost-effectiveness analyses (CEAs) based on a static price or the estimated price at market launch. Recent publications suggest incorporating dynamic pricing. To test the feasibility and importance of including dynamic pricing, we compared the standard static approach to four dynamic scenarios by replicating US-based HTA evaluations with dynamic pricing inputs. METHODS: The four case examples included omalizumab (Xolair®) for the treatment of allergic asthma, elagolix (Orilissa®) for the treatment of endometriosis, ocrelizumab (Ocrevus®) for the treatment of primary progressive multiple sclerosis (PPMS), and dupilumab (Dupixent®) for the treatment of atopic dermatitis (AD). The primary outcome was the relative percentage change in incremental cost-effectiveness ratios (ICERs) per quality-adjusted life-year (QALY) for two dynamic pricing scenarios versus static pricing. Secondary outcomes included the absolute difference in ICERs versus base-case and an assessment of decision uncertainty. RESULTS: Base-case ICERs were $327,000, $102,000, $700,000, and $102,000 for allergic asthma, endometriosis, PPMS, and AD, respectively. Across scenarios and case examples, the range of ICERs versus base-case varied from decreases of 56% to increases of 232%. The absolute difference in ICERs versus base-case ranged from decreases of $120,000 to increases of $758,000. Conclusions on cost effectiveness were altered in 2/16 scenarios across the four case examples. CONCLUSIONS: Given the decision context that US payers face, with prices varying over time, findings suggest further research to reduce uncertainty around price trajectories, as well as conducting or updating multiple assessments over the lifecycle of pharmaceutical products.

Cost comparison of dupilumab and omalizumab for the treatment of severe allergic asthma patients from the Brazilian private healthcare system perspective / Comparação dos custos de dupilumabe e omalizumabe para o tratamento de pacientes com asma alérgica grave na perspectiva do sistema de saúde privado brasileiro

Objective: To compare the costs of dupilumab and omalizumab for treating severe allergic asthma patients from the perspective of the Brazilian private healthcare system. Methods: Using clinical and demographic inputs from the literature, we simulated a cohort of 5,000 severe allergic asthma patients and estimated the treatment cost with omalizumab. Results: In the simulated cohort, 81.3% were female, the mean body weight was 75.1 kg (SD 13.1), and the mean serum IgE was 532 IU/mL (SD 688). All patients were eligible for treatment with dupilumab, but 830 (16.6%) were ineligible for treatment with omalizumab due to serum IgE level and/or body weight combinations, according to the product label. Over four weeks, the mean dose of omalizumab was 537 mg (SD 285). The annual mean per-patient cost for treatment with omalizumab was BRL 110,783.89 (SD 58,385.81), ranging from BRL 31,797.49 to BRL 246,643.15. The treatment cost with dupilumab is BRL 111,724.21 for the first year and BRL 107,599.91 for subsequent years. Conclusions: We observed slightly lower mean treatment costs with dupilumab than with omalizumab. However, while the treatment cost with dupilumab is fixed and predictable, the treatment cost with omalizumab is highly variable, depending on patients' characteristics. Health managers should consider these findings for reimbursement and clinical protocol development decisions.

Objetivo: Comparar os custos de dupilumabe e omalizumabe para o tratamento de pacientes com asma alérgica grave na perspectiva do sistema de saúde privado brasileiro. Métodos: Utilizando parâmetros clínicos e demográficos a partir de dados da literatura, simulamos uma coorte com 5.000 pacientes com asma alérgica grave e estimamos o custo de tratamento com o omalizumabe. Resultados: Na coorte simulada, 81,3% eram do sexo feminino, com peso médio de 75,1 kg (DP 13,1) e IgE sérica de 532 IU/mL (DP 688). Todos os pacientes eram elegíveis para o tratamento com dupilumabe, porém 830 (16,6%) não eram elegíveis para o tratamento com omalizumabe devido a combinações específicas de IgE sérica e/ou peso corporal, de acordo com a bula do produto. Para o período de 4 semanas, a dose média de omalizumabe foi de 537 mg (DP 285). O custo médio anual por paciente do tratamento com omalizumabe foi de R$ 110.783,89 (DP 58.385,81), variando de R$ 31.797,49 a R$ 246.643,15. O custo do tratamento com dupilumabe é de R$ 111.724,21 no primeiro ano e R$ 107.599,91 nos anos seguintes. Conclusões: Foi observado que o custo médio do tratamento com dupilumabe é ligeiramente menor que o custo com omalizumabe. Todavia, enquanto o custo do tratamento com dupilumabe é fixo e previsível, o custo do tratamento com omalizumabe é altamente variável, dependendo de características dos pacientes. Esses achados devem ser considerados pelos gestores de saúde para decisões sobre reembolso e desenvolvimento de protocolos clínicos.

Inclusão de nova apresentação de omalizumabe (150 mg/mL) solução injetável em seringa preenchida para tratamento da asma alérgica grave não controlada apesar do uso de corticoide inalatório (CI) associado a um beta2- agonista de longa ação (LABA) / Inclusion of new presentation of omalizumab (150 mg/mL) solution for injection in pre-filled syringe for treatment of severe allergic asthma that is uncontrolled despite use of inhaled corticosteroids (ICS) associated with a beta2- long-acting agonist (LABA)

INTRODUÇÃO: A asma é uma doença inflamatória crônica das vias aéreas inferiores que se caracteriza por aumento da responsividade dessas vias a diferentes estímulos, com consequente obstrução ao fluxo aéreo, de forma recorrente e reversível. A OMS estima que cerca de 235 milhões de pessoas sofrem de asma. No Brasil, a asma foi a 3ª causa de internação hospitalar pelo SUS em 2008, com cerca de 300.000 hospitalizações naquele ano. Em 2013, ocorreram 129.728 internações e 2.047 mortes. Já em 2018, o número de internações foi de aproximadamente 87.000. De acordo com o PCDT de asma, do Ministério da Saúde, o omalizumabe é uma terapia inespecífica anti-IgE indicada exclusivamente para adultos e crianças com pelo menos 6 anos de idade com asma alérgica, moderada a grave (etapas IV e V), cujos sintomas são inadequadamente controlados apesar do uso de corticoide inalatório associado a um beta-2 agonista de longa ação. RECOMENDAÇÃO PRELIMINAR: Os membros do Plenário, presentes na 111ª Reunião Ordinária da Conitec, no dia 03 de agosto de 2022, deliberaram por unanimidade que a matéria fosse disponibilizada em consulta pública com recomendação preliminar favorável à inclusão da nova apresentação de omalizumabe (150 mg/mL) solução injetável em seringa preenchida, ao SUS, para tratamento da asma alérgica grave não controlada apesar do uso de corticoide inalatório (CI) associado a um beta2-agonista de longa ação (LABA). A matéria foi disponibilizada em consulta pública. CONSULTA PÚBLICA: Foram recebidas 14 contribuições, sendo nove pelo formulário de experiência e opinião e cinco pelo formulário técnico-científico. Os nove respondentes do formulário de experiência e opinião apresentaram-se favoráveis à recomendação inicial da Conitec. Os participantes mencionaram a facilidade de administração do omalizumabe em seringa preenchida, a melhora na qualidade de vida e a necessidade de incorporação dessa apresentação do medicamento no SUS. Os benefícios desse formato de administração foram mencionados como uma facilidade do medicamento. No formulário para contribuições técnico-científicas quatro não apresentaram argumentação técnica sobre as evidências, mas argumentação de cunho pessoal acerca do uso da tecnologia, três foram positivas à incorporação. A contribuição enviada pela empresa fabricante do omalizumabe teceu comentários sobre as justificativas científicas e sobre o impacto orçamentário apresentadas na apreciação inicial da matéria, reforçando que não haverá ônus ao Ministério da Saúde na incorporação da nova apresentação de omalizumabe. RECOMENDAÇÃO FINAL DA CONITEC: Os membros do Plenário presentes na 113ª Reunião Ordinária da Conitec, realizada no dia 06 de outubro de 2022, deliberaram por unanimidade, recomendar a incorporação da nova apresentação de omalizumabe (150 mg/mL) solução injetável em seringa preenchida, ao SUS, para tratamento da asma alérgica grave não controlada apesar do uso de corticoide inalatório (CI) associado a um beta2-agonista de longa ação (LABA). Não foram adicionadas evidências, durante a Consulta Pública, que alterassem a recomendação preliminar da Comissão. Foi assinado o Registro de Deliberação nº 774/2022. DECISÃO: Incorporar, no âmbito do Sistema Único de Saúde - SUS, a nova apresentação de omalizumabe (150 mg/mL), solução injetável em seringa preenchida, para tratamento da asma alérgica grave não controlada apesar do uso de corticoide inalatório (CI) associado a um beta2- agonista de longa ação (LABA), conforme a Portaria nº 143, publicada no Diário Oficial da União nº 214, seção1, página 92, em 11 de novembro de 2022.

Characterization and pre-clinical assessment of a proposed biosimilar to its originator Omalizumab.

Omalizumab is an anti-IgE monoclonal antibody (mAb) approved for the treatment of moderate-to-severe asthma. Herein, we report physicochemical, biological, pharmacological, and toxicological characteristics of an Omalizumab biosimilar mAb named KA. We show that KA and its originator present only minimum differences. Their charge heterogeneity and primary, secondary structures are similar. The two molecules are comparable regarding in vitro activity, including molecular binding and cell-based inhibition. Pharmacological and toxicological properties were assessed using a mouse model of allergy and cynomolgus monkeys, and we determined that the efficacy, safety, and pharmacokinetic characteristics of KA are comparable to its originator. Our data, which demonstrated that KA has similar activity to the Omalizumab reference product in relevant preclinical models, calls for a clinical evaluation of its bio-similarity.

Trends in the Cost and Utilization of Omalizumab in the Medicare Population: 2013-2017.

Background: Omalizumab has been demonstrated to be effective in treating chronic spontaneous urticaria (CSU) and was FDA approved for this indication in 2014. Previous work has shown that access to injectable biologics varies across US counties. In the present study we evaluate geographic and temporal trends in the utilization of omalizumab in the Medicare population by dermatologists, with its use by allergists and pulmonologists as comparators. Methods: We analyzed year-over-year trends in omalizumab utilization across geographic regions using the Medicare Provider Utilization and Payment Data: Part D files. Results: Utilization of omalizumab by dermatologists increased rapidly after its FDA approval, from 0.08 claims/100,000 enrollees totaling $209/100,000 enrollees in 2014 to 1.45 claims/100,000 enrollees totaling $3115/100,000 enrollees in 2017. Nonetheless, prescribing dermatologists were present in only 2.8% (95% Confidence Interval (CI): 2.0%-3.9%) and 0.2% (95% CI: 0.0%-0.5%) of metropolitan and non-metropolitan counties, respectively, in 2017, demonstrating limited availability, especially in non-metropolitan counties. Similarly, prescribers of any specialty were available in 32.9% (95% CI: 30.2%-35.6%) and 3.8% (95% CI: 3.1%-4.8%) of metropolitan and non-metropolitan counties, respectively, in 2017. Conclusions: Our data suggest that despite increasing omalizumab utilization, there remains a lack of access across many counties, particularly in non-metropolitan regions. Efforts to expand omalizumab prescriber accessibility in these counties may improve outcomes for patients with CSU.

Cost-effectiveness of personalized omalizumab dosing for chronic spontaneous urticaria.

The licensed dose for omalizumab within Europe for chronic spontaneous urticaria (CSU) is 300 mg every 4 weeks, and is based on the most effective dose identified in clinical trials. However, many patients require longer-term treatment with omalizumab and there is limited guidance on how to manage these patients. We report on a large cohort of 357 patients with CSU who have been treated over a 10-year period on a personalized dosing regimen. Our results showed a 4% reduction in drug cost for this personalized dosing regimen compared with having all patients on the standard regimen of omalizumab 300 mg every 4 weeks. In addition, by increasing the dose, we were able to treat 22% of patients more effectively, using the principle aim of zero CSU symptoms; prior to this regimen, these patients had been achieving only partial response. Omalizumab doses and frequency should be adjusted depending on clinical response to allow for improved benefits for both patients and healthcare systems.

Prevalence, Management, and Anaphylaxis Risk of Cold Urticaria: A Systematic Review and Meta-Analysis.

BACKGROUND: Cold urticaria is a subtype of chronic inducible urticaria (CIndU) associated with significant morbidity and a risk for anaphylaxis. Few studies have assessed the prevalence, management, and prevalence of associated anaphylaxis of cold urticaria. OBJECTIVES: To evaluate the prevalence of cold urticaria among CIndU and chronic urticaria (CU) cases, to assess the management of cold urticaria, and to determine the prevalence of associated anaphylaxis. METHODS: We searched PubMed and EMBASE for studies pertaining to cold urticaria and/or CIndU published in the past 10 years. We conducted meta-analyses to evaluate the prevalence of cold urticaria among CIndU and CU cases, the management of cold urticaria with H1-antihistamines and omalizumab, and the prevalence of associated anaphylaxis. RESULTS: Twenty-two studies were included in the systematic review and 14 in the meta-analysis. The pooled prevalence of cold urticaria among patients with CU and CIndU was 7.62% (95% confidence interval [CI], 3.45% to 15.99%; I2 = 98%) and 26.10% (95% CI, 14.17% to 43.05%; I2 = 97%), respectively. Cold urticaria was managed by H1-antihistamines in 95.67% (95% CI, 92.47% to 97.54%; I2 = 38%) of patients and omalizumab in 5.95% (95% CI , 2.55% to 13.27%; I2 = 83%) of patients. The pooled prevalence of anaphylaxis among patients with cold urticaria was 21.49% (95% CI, 15.79% to 28.54%; I2 = 69%). CONCLUSIONS: Cold urticaria constitutes an appreciable proportion of CIndU and CU cases and is predominantly managed with H1-antihistamines; few patients receive omalizumab. Anaphylaxis is common, and an epinephrine autoinjector prescription may be considered.

Cost­effectiveness of tiotropium versus omalizumab for uncontrolled allergic asthma.

OBJECTIVE: In patients with uncontrolled asthma, despite management with high doses of inhaled corticosteroids, the additional use of omalizumab and tiotropium is recommended. Omalizumab is an expensive medication and doubts arise as to whether the benefit of this drug outweighs the additional expense of the drug. The purpose of this study was to assess the cost-effectiveness of tiotropium versus omalizumab as add-on therapies to ICS + LABA for patients with uncontrolled allergic asthma. METHODS: A probabilistic Markov model was created to estimate the cost and quality-adjusted life years (QALYs) of patients with uncontrolled allergic asthma in Colombia. Total costs and QALYs of three interventions including standard therapy (ICS + LABA), add-on therapy with tiotropium, and add-on therapy with omalizumab, were calculated over a 10-year time horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000. RESULTS: The model showed that tiotropium was associated with lower cost than standard therapy and omalizumab (US$5590 vs. US$5693 vs. U$18,154 average annual cost per patient), and higher QALYs (11.8 vs. 11.3 vs. 11.9) average per patient), showing dominance respect to standard therapy. The probability that tiotropium provides a more cost-effective use of resources compared with standard therapy exceeds 99% for willingness-to-pay threshold. CONCLUSION: Add-on therapy with tiotropium was a cost-effective alternative to omalizumab and standard therapy for uncontrolled allergic asthma. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other middle-income countries.

Cost-Effectiveness Analysis of Omalizumab for Severe Allergic Asthma in Japan Using Real-World Evidence.

OBJECTIVES: Omalizumab is a recommended add-on therapy for patients with severe allergic asthma who remain uncontrolled despite treatment with standard of care (SoC). This study evaluated the cost-effectiveness of omalizumab compared with SoC applying real-world clinical outcomes in adult patients with severe allergic asthma in Japan. METHODS: A validated Markov model was adapted for Japan and compared the cost-effectiveness of omalizumab as an add-on therapy to SoC versus SoC alone using the most recently updated price of omalizumab. A Japanese real-world postmarketing surveillance and a pivotal randomized clinical trial were used as inputs for clinical effectiveness. Japanese life tables and literature were accessed for mortality data and unit costs were extracted from a Japanese insurance claims database. Quality of life data were retrieved from the clinical trial. RESULTS: In the base case, the incremental cost-effectiveness ratio for omalizumab add-on therapy was ¥2.85 million per quality-adjusted life-year gained (approximately €21 000; 1€ = ¥133.26) compared with SoC alone. The model appeared to be most sensitive to changes in clinically significant severe exacerbation fatality, day-to-day asthma symptom utilities for SoC, discount rates for benefits, day-to-day asthma symptom utilities for omalizumab responders, time horizon, and the annual cost of omalizumab. The results of the probabilistic sensitivity analysis showed that the probability of omalizumab being cost-effective was 93% to 98% at a threshold of ¥5 to ¥6 million (willingness-to-pay for 1 quality-adjusted life-year). CONCLUSIONS: Omalizumab add-on therapy is cost-effective compared with SoC alone in Japan in severe allergic asthma population who are uncontrolled with high-dose inhaled corticosteroid and other controllers.