Cost-effectiveness of omalizumab for the treatment of chronic spontaneous urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a skin disease with itchy hives and/or angio-oedema that last for at least 6 weeks without an obvious external trigger. OBJECTIVES: To determine the cost-effectiveness of omalizumab relative to standard of care (SoC; up to four times the daily dose of H1 -antihistamines) in the Netherlands from a societal perspective. METHODS: The Markov model used consisted of five health states based on Urticaria Activity Score over 7 days. Model settings and characteristics of the Dutch patient population were based on an online survey among clinical experts and were validated during an expert committee meeting. Transition probabilities were derived from the GLACIAL trial. Healthcare consumption, quality of life (using EuroQol-5D) and productivity losses were derived from a burden-of-illness study (ASSURE-CSU) among 93 Dutch patients. Healthcare consumption and productivity losses were evaluated using the Dutch costing manual. The comparator treatment was SoC, consisting of (updosed) antihistamines. A 10-year time horizon was used. RESULTS: The incremental cost-effectiveness ratio (ICER) of omalizumab vs. SoC was €17 502 per quality-adjusted life-year (QALY) gained. Productivity costs played an important role in the value of the ICER; discarding productivity costs resulted in an ICER of €85 310 per QALY. CONCLUSIONS: Omalizumab is cost-effective compared with SoC. The outcomes of this study were used to establish omalizumab as third-line therapy in the Dutch treatment guidelines for CSU.

Health-care utilization and costs with fluticasone propionate and fluticasone propionate/salmeterol in asthma patients at risk for exacerbations.

Although studies have established that adding long-acting beta agonists (LABA) to inhaled corticosteroid (ICS) monotherapy among patients with inadequately controlled asthma is associated with better outcomes than increasing ICS dosage, outcomes with ICS versus fixed-dose ICS/LABA combination among patients with recent asthma exacerbation or frequent use of rescue medication are unavailable. This study was designed to compare health-care utilization/costs among patients with recent asthma exacerbation or frequent rescue medication use who received fluticasone propionate (FP) alone versus fixed-dose FP/salmeterol combination (FSC). A retrospective cohort study was conducted using a large health insurance data set. Patients with one or more claims with asthma diagnosis, two or more prescriptions for FSC (250/50- or 100/50-mg formulations) or FP (220- or 110-mg formulations), and one or more asthma exacerbations or five or more short-acting beta agonist (SABA) prescriptions within 1 year before initial receipt of study medications were included. Health-care utilization/costs and controller therapy compliance were compared for patients receiving FSC versus FP using multivariate regression analysis controlling for FP dose and baseline characteristics. A total of 7779 patients met inclusion criteria (5769, FSC, and 2010, FP) with comparable mean follow-up (FSC, 685 days; FP, 670 days; p = 0.151). Controlling for FP dosage and baseline characteristics, FSC patients had lower risks of asthma-related exacerbations, fewer SABAs and systemic corticosteroids, higher costs of asthma medications and total asthma-related health care, and lower total asthma-related health-care costs excluding study medication cost. In asthma patients with recent exacerbation or frequent SABA use, receipt of FSC reduced asthma-related exacerbation risks and rescue medication use versus receipt of FP.

Chronic idiopathic urticaria: treatment with omalizumab.

Chronic idiopathic urticaria (CIU) is a common autoimmune skin condition characterized by spontaneously recurring hives for 6 weeks or longer. The new terminology used for CIU in most countries including Canada is chronic spontaneous urticaria (CSU). CSU is associated with significant psychosocial morbidity with a markedly negative impact on overall quality of life. Conventional approaches with antihistamines, even at high doses, is effective in about 50% of patients suffering from CSU. A new treatment option, omalizumab, a humanized monoclonal antibody against the Fc domain of IgE, has undergone the scrutiny of randomized research studies evaluating the efficacy in CSU. This editorial reviews mechanisms of action of omalizumab, efficacy, cost and potential side effect profile. Omalizumab has emerged as a very promising treatment option for patients with CSU. Future research is necessary to establish standardized protocols related to dosing as well as monitoring possible adverse effects of long-term treatment.

Subcutaneous immunotherapy in Northern Israel: efficacy and safety.

BACKGROUND: The efficacy of subcutaneous immunotherapy for the treatment of allergic rhinitis, allergic conjunctivitis, allergic asthma and stinging insect hypersensitivity has been demonstrated in several studies. OBJECTIVES: To investigate the effectiveness and side effects of immunotherapy in Israel and the relationship between local and systemic side effects. METHODS: This retrospective study was based on patient records and a computerized database for drug dispensing over a 5 year period. Success was rated as partial or complete. Side effects were classified as local or systemic. Systemic side effects were further classified according to severity, as mild (cutaneous), moderate (respiratory symptoms), or severe (cardiovascular). RESULTS: Of the 135 patients on aero-allergen immunotherapy who reached maintenance, 120 (88.9%) exhibited complete or partial improvement and 15 (11.1%) did not improve. All of the 44 patients on hymenoptera immunotherapy reached effective maintenance doses. The mean percent side effects calculated per treatment (injection) were 2.49 for local and 1.58 for a systemic reaction during the build-up phase, and 1.13 and 1.12 during the maintenance phase, respectively. Rates of systemic reactions were 1.3% for cutaneous, 1.14% for respiratory and 0.97% for cardiovascular reactions during the build-up phase, and 1.11%, 0.53%, and 0.51% during the maintenance phase, respectively. The odds of systemic reactions were significantly higher in patients with local reactions both in the build-up phase (P = 0.03) and in the maintenance phase (P = 0.0003). The number of annual medications dispensed per patient decreased from 31.5 to 26.0 during the first year after reaching maintenance, and to 22.5 in the second year. Pharmaceutical costs were 67% lower 1 year after the start of the maintenance phase, compared to the year before the start of immunotherapy, and 63% lower in the second year (P = NS). CONCLUSIONS: Immunotherapy was effective and safe. Recognizing the benefits and safety of immunotherapy by physicians and health authorities is necessary to provide better care for allergic patients.

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

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

[Cost-effectiveness analysis of pre-seasonal medication for cedar pollinosis in Japan].

Pre-seasonal medication is recommended for cases of cedar pollinosis that are expected to manifest severe symptoms during the season, according to the standard clinical guideline in Japan. This study aims to appraise the value for money of additional costs that accompany the choice of pre-seasonal medication from payer's perspective. Based on the 12 reports of controlled clinical trials with Symptom Score (SS) and Medication Score (MS) comparing pre-seasonal medication with intra-seasonal symptomatic medication, 15 incremental cost-effectiveness ratios (ICERs) and 4 integrated ICERs of each group of targeted agents are estimated. Incremental effects are estimated by reading SS charts, and incremental costs are estimated by reading MS charts and using National Health Insurance Medical Fee Schedule and National Health Insurance Drug Price Standard. Estimated ICERs range from ¥322,195 per quality-adjusted life-year (QALY) to ¥57,088,063 per QALY. Integrated ICERs are: ¥1,128,286 per QALY for 2nd generation histamine H(1) receptor antagonists, ¥2,248,018 per QALY for leukotriene receptor antagonists, ¥2,692,911 per QALY for prostaglandin D(2) and thromboxane A(2) receptor antagonists, ¥1,150,943 per QALY for Th2 cytokine suppressors, and ¥1,291,341 per QALY for all agents. Pre-seasonal medication for cedar pollinosis is cost-effective regardless of the choice of the prophylactic agent among 2nd generation histamine H(1) receptor antagonists, leukotriene receptor antagonists, prostaglandin D(2) and thromboxane A(2) receptor antagonists, or Th2 cytokine suppressors, taking the suggested threshold of ¥5,000,000 per 1 QALY gain in Japan. The use of 2nd generation histamine H(1) receptor antagonists and Th2 cytokine suppressors are found more favourable.

Comparison of corticosteroid nasal sprays in relation to concomitant use and cost of other prescription medications to treat allergic rhinitis symptoms: retrospective cohort analysis of pharmacy claims data.

BACKGROUND AND OBJECTIVE: Intranasal corticosteroids are considered to be highly effective in patients with perennial or seasonal allergic rhinitis. Multiple intranasal corticosteroid products are available; however, an intranasal corticosteroid that treats nasal and ocular seasonal allergic rhinitis symptoms may be more cost effective by reducing the need for concomitant drugs. The purpose of this study was to compare the utilization and costs of concomitant allergic rhinitis drugs among commonly used branded intranasal corticosteroid drugs. METHODS: Pharmacy claims data between 1 April 2006 and 31 January 2008 were obtained from the Wolters Kluwer SourceLx dataset. Patients with at least one pharmacy claim for a branded intranasal corticosteroid agent (fluticasone furoate, budesonide, mometasone or triamcinolone) during the index period of 1 April 2007 through 31 July 2007 were included. Study outcomes assessed were time to concomitant use of prescription allergic rhinitis drugs (other than intranasal corticosteroids) and costs of those medications and intranasal corticosteroid drugs during a 60-day post-index period. RESULTS: A total of 793 349 patients were included in the study. At index, a majority of the patients were using mometasone (62.9%), followed by triamcinolone (21.1%), budesonide (15.1%) and fluticasone furoate (1.0%). After controlling for other covariates, patients receiving fluticasone furoate had on average a 21% lower risk of concomitant prescription allergic rhinitis drug use (adjusted hazard ratio [HR] 0.79; 95% CI 0.75, 0.83) compared with the other three branded intranasal corticosteroid agents. Compared with fluticasone furoate, all other branded intranasal corticosteroid agents incurred statistically significant higher costs of concomitant allergic rhinitis drugs (6.3%, p = 0.002), resulting in increased costs to health plans of $US5-$US6 per patient over a 60-day period. Mean intranasal corticosteroid costs per patient during the 60-day follow-up period were lowest for budesonide ($US70.15), followed by fluticasone furoate ($US70.86), triamcinolone ($US73.23) and mometasone ($US75.48). CONCLUSION: In this cohort of intranasal corticosteroid users, fluticasone furoate was shown to reduce the need for concomitant prescription allergic rhinitis medications compared with other leading branded intranasal corticosteroid therapies, resulting in lower costs per patient and potentially leading to significant savings for health plans.

Cost-effectiveness of omalizumab in adults with severe asthma: results from the Asthma Policy Model.

BACKGROUND: Omalizumab (trade name Xolair) is approved by the US Food and Drug Administration for treatment of moderate-to-severe allergic asthma. Given the high acquisition cost of omalizumab, its role and cost-effectiveness in disease management require definition. OBJECTIVE: We sought to identify the clinical and economic circumstances under which omalizumab might or might not be a cost-effective option by using a mathematic model. METHODS: We merged published data on clinical and economic outcomes (including acute event incidence, frequency/severity of hospitalizations, and health-related quality of life) to project 10-year costs, quality-adjusted life years (QALYs), and cost-effectiveness of treatment with omalizumab in addition to inhaled corticosteroids. Sensitivity analyses were conducted by using input data ranges from a variety of sources (published clinical trials and observational databases). RESULTS: For patients with baseline acute event rates, omalizumab conferred an additional 1.7 quality-adjusted months at an incremental cost of $131,000 over a 10-year planning horizon, implying a cost-effectiveness ratio of $821,000 per QALY gained. For patients with 5 times the baseline acute event rate, the cost-effectiveness ratio was $491,000 per QALY gained. The projected cost-effectiveness ratio could fall within a range of other programs that are widely considered to be cost-effective if the cost of omalizumab decreases to less than $200. CONCLUSION: Omalizumab is not cost-effective for most patients with severe asthma. The projected cost-effectiveness ratios could fall within a favorable range if the cost of omalizumab decreases significantly. CLINICAL IMPLICATIONS: Based on the high cost of omalizumab, it is especially important that clinicians explore alternative medications for asthma before initiating omalizumab.

[Allergic rhinitis--an epidemiological, economical and social problem of the XXI century]. / Alergiczny niezyt nosa--problem epidemiologiczny, ekonomiczny i spoleczny XXI wieku.

Exposure of nasal mucosa to various allergic and/or non-allergic stimuli might result in rhinitis. Allergic rhinitis affects 10-25% of population making it the most prevalent allergic disorder. Seasonal and perennial allergic rhinitis affect up to 30% and 10% of pediatric population, respectively. Prevalence of allergic rhinitis varies between studies: in Poland, Breborowicz et al. reported allergic rhinitis in 16.7% of children aged 6-7, whereas Emeryk et al. observed perennial allergic rhinitis in 3.6% and seasonal allergic rhinitis in 6.2% of 8-15 year olds. Allergic rhinitis similarly to other diseases results in direct, indirect and hidden costs. In the USA (2002) direct costs were estimated at $4.195 billions and indirect at $665 millions (total of $4.863 billions). Allergic rhinitis co-exists with multiple respiratory conditions, significantly increasing treatment costs incurred by patients' and places additional burden on public finances. It also has a detrimental effect on patients' and their families' quality of life. Allergic rhinitis--although non-life threatening--significantly worsens quality of daily life and as such should be perceived as a serious medical condition not only by patients but also by medical professionals who are in position to diagnose it and implement appropriate therapeutic interventions.

Pharmacoeconomic assessment of specific immunotherapy versus current symptomatic treatment for allergic rhinitis and asthma in France.

OBJECTIVES: The therapeutic benefit of specific immunotherapy (SIT) in allergic rhinitis and asthma has been endorsed by expert consensus. This study compared the cost/efficacy (C/E) of SIT with current symptomatic treatments (CST) for allergic rhinitis and asthma. METHODS: A C/E analysis was performed using a decision tree model. The decision tree and medical and economic hypotheses were defined by a panel of experts. The perspective adopted was that of the French Social Security. The costs and efficacy of SIT and CST were compared for dust-mite and pollen allergies, in adults and children. Direct medical costs included diagnosis and follow-up, consultations, CST and SIT. End-point economic criteria were cost per stabilised patient and cost per asthma case avoided. A sensitivity analysis was performed for each model. RESULTS: In adults, the incremental costs per asthma case avoided with injectable SIT were 393 Euro and 1327 Euro for dust-mite and pollen allergy, respectively, over a 6-year period. For sublingual SIT, the costs per asthma case avoided were 3158 Euro and 1708 Euro, respectively. In children, over a 7-year period, the incremental costs per asthma case avoided with injectable SIT were 583 Euro and 597 Euro for dust-mite and pollen allergy, respectively. For sublingual SIT the incremental costs were 3938 Euro and 824 Euro. CONCLUSION: Compared to CST, SIT is a cost-effective treatment in pollen and dust-mite-induced allergic rhinitis and asthma. Sublingual SIT is an attractive option in pollen-induced rhinitis, particularly in children. SIT appears to be an economically relevant strategy compared to CST.

Cost Utility of Omalizumab Compared with Standard of Care for the Treatment of Chronic Spontaneous Urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) negatively impacts patient quality of life and productivity and is associated with considerable indirect costs to society. OBJECTIVE: The aim of this study was to assess the cost utility of add-on omalizumab treatment compared with standard of care (SOC) in moderate or severe CSU patients with inadequate response to SOC, from the UK societal perspective. METHODS: A Markov model was developed, consisting of health states based on Urticaria Activity Score over 7 days (UAS7) and additional states for relapse, spontaneous remission and death. Model cycle length was 4 weeks, and total model time horizon was 20 years in the base case. The model considered early discontinuation of non-responders (response: UAS7 ≤6) and retreatment upon relapse (relapse: UAS7 ≥16) for responders. Clinical and cost inputs were derived from omalizumab trials and published sources, and cost utility was expressed as incremental cost-effectiveness ratios (ICERs). Scenario analyses included no early discontinuation of non-responders and an altered definition of response (UAS7 <16). RESULTS: With a deterministic ICER of £3183 in the base case, omalizumab was associated with increased costs and benefits relative to SOC. Probabilistic sensitivity analysis supported this result. Productivity inputs were key model drivers, and individual scenarios without early discontinuation of non-responders and adjusted response definitions had little impact on results. ICERs were generally robust to changes in key model parameters and inputs. CONCLUSIONS: In this, the first economic evaluation of omalizumab in CSU from a UK societal perspective, omalizumab consistently represented a treatment option with societal benefit for CSU in the UK across a range of scenarios.

Comparison of efficacy, safety, and cost-effectiveness of montelukast-levocetirizine and montelukast-fexofenadine in patients of allergic rhinitis: A randomized, double-blind clinical trial.

OBJECTIVES: Allergic rhinitis (AR) is a global health problem. Almost 10%-25% of population worldwide is affected by AR. Oral/intranasal H1-antihistamine, decongestants, leukotriene receptor antagonists, and intranasal corticosteroids are the pillars in the management of AR. The combination therapy of montelukast with antihistaminic provides enhancing and complimentary effects, thereby reducing the symptoms effectively, but there are scanty data regarding the comparisons of combinations. Therefore, we aimed to compare the efficacy, safety, and cost-effectiveness of montelukast-levocetirizine and montelukast-fexofenadine combination in patients of AR. MATERIALS AND METHODS: Seventy patients with AR participated in a prospective, randomized, double-blind, parallel, active-controlled, comparative 4-week trial. The patients between the age group of 18-65 years of either gender having moderate-severe intermittent or mild persistent AR were included in the study. The study inclusion criteria required the patients with total nasal symptom score (TNSS) of 5 or higher. The patients were randomly divided into two treatment groups with montelukast-levocetirizine (10 mg and 5 mg) in one group and montelukast-fexofenadine (10 mg and 120 mg) in another group. TNSS parameter was the main effectiveness parameter. RESULTS: Evaluation of TNSS revealed significant difference (P < 0.05) when compared from baseline to 4th week in both groups. The mean change of TNSS, i.e., 9.46 was significant (P < 0.05) in montelukast-fexofenadine group. The cost-effectiveness ratio was less in montelukast-levocetirizine group than in montelukast-fexofenadine group. CONCLUSION: The decrease in TNSS was more in montelukast-fexofenadine group, but the cost-effectiveness is more with montelukast-levocetirizine combination.

Anti-IgE therapy with omalizumab in asthma and allergic rhinitis.

The pharmacology, efficacy, dosage, adverse effects, and economics of anti IgE (omalizumab) are discussed. Omalizumab is the generic name for the human/murine chimeric (recombinant humanized) monoclonal IgG antibody. Anti-IgE prevents IgE from attaching to effector cells, and thereby blunts IgE-mediated inflammatory responses. After subcutaneous administration its absorption is slow, reaching peak concentration in serum after an average of 7-8 days. At recommended doses, serum free IgE levels decrease within 1 hour following the first dose and are maintained between doses. Dose and dosing frequency are adjusted according to body mass and serum total IgE concentration before the start of treatment. Omalizumab administered subcutaneously is an effective treatment for add-on therapy in patients with poorly controlled, moderate-to-severe allergic asthma and allergic rhinitis (adults and adolescents > 12 years). It reduces the requirement for inhaled corticosteroids while protecting against disease exacerbation. Omalizumab is well tolerated, but the safety profile requires long-term assessment in adults as well as in children.

Medication-related expenditures by individuals with allergic rhinitis in Nigeria.

OBJECTIVE: To assess the medication-related expenditures in individuals with allergic rhinitis (AR) and identify contributory factors that affect these expenditures. STUDY DESIGN: Cross-sectional study from August 2013 to January 2014. SETTING: Kwara state has 16 local government areas, a total land mass of 36,825 km(2), and a population of 2,591,555. SUBJECTS AND METHODS: Of the 308 adult subjects, 66 had AR using the Score for Allergic Rhinitis (SFAR). Information on medication-related expenditure and associated factors in AR was obtained using a structured questionnaire. Descriptive and comparative analyses between AR and non-AR subjects were performed using an independent-sample t test and χ(2) test. Factors associated with cost of care were assessed using logistic regression analysis. RESULTS: The AR crude prevalence rate was 21.4%. Of the subjects, the mean ± SD age was 37.6 ± 10.0 years, and 87.9% were married, 72.7% were self-employed, and 69.7% were in the low socioeconomic class. In total, 69.7% had intermittent symptoms, while 66.7% had a positive family history of allergy. Polypharmacy care was employed in 76.1%, and 30.3% had comorbidity with asthma. The mean monthly income was 842 US dollars (USD), while the mean monthly cost of care was 81 USD, constituting 9.6% of mean monthly income. All payments were through out-of-pocket-expenses. Factors associated with convenience of cost of care were positive family history (odds ratio [OR], 7.93; P = .021) and presence of intermittent symptoms (OR, 9.36; P = .013). CONCLUSION: The medication-related expenditure of AR is burdensome with an average expenditure of almost 10% of monthly income.

A comparison of costs and efficacy of intranasal fluticasone propionate and terfenadine tablets for seasonal allergic rhinitis.

This paper compares cost-efficacy ratios for intranasal fluticasone propionate and terfenadine tablets within a sample of patients with seasonal allergic rhinitis symptoms due to mountain cedar allergy. Efficacy was assessed using secondary data analysis of patient ratings of symptoms and their overall assessment of response to treatment within a previously conducted clinical trial. Costs include direct costs of the drugs used for therapy. Patients with documented mountain cedar allergy who were 12 years of age or older (N = 232) had been randomized to either receive intranasal fluticasone propionate, terfenadine, or placebo. The cost-efficacy ratios for intranasal fluticasone propionate 200 micrograms once daily were more favorable than the ratios for terfenadine 60 mg twice daily. This relationship remained throughout the sensitivity analysis. Because intranasal fluticasone propionate is only available in a fixed package size, the number of efficacy-adjusted days of terfenadine therapy that could be purchased to reach break-even costs for a 30-day supply of fluticasone was calculated. Cost efficacy-adjusted days ranged from 11 to 18 days. If cost-efficacy adjustments are not conducted, the upper end of the range increases from 18 to 22 days, since 22 days of terfenadine could be purchased for the price of a 30-day supply of intranasal fluticasone propionate. Depending on which of the efficacy measures the reader believes, if patients use terfenadine for longer than 11 to 22 days, fluticasone propionate is the more cost-efficacious choice. Because most allergies are seasonal and allergy seasons typically last longer than 11 to 22 days, it is likely that fluticasone propionate will frequently be the more cost-efficacious choice in the patient population represented in this study.