Outcomes before and after treatment escalation to Global Initiative for Asthma steps 4 and 5 in severe asthma.

BACKGROUND: Little is known about health outcomes in severe asthma reflected by Global Initiative for Asthma steps 4 and 5. OBJECTIVE: To analyze control, risk, economic, and health resource use (HRU) outcomes associated with treatment escalation to Global Initiative for Asthma steps 4 and 5. METHODS: This was a before-vs-after retrospective cohort study of patients (12-75 years old) with asthma newly initiated to omalizumab, high-intensity corticosteroids (HICS; ≥1,000 µg/day of inhaled fluticasone equivalent or oral prednisone), or high-dose inhaled corticosteroid (HDICS; ≥500 to <1,000 µg/day of fluticasone equivalent) using 2002 to 2011 MarketScan data. Poisson regression was used to model HRU outcomes; Tobit regression was used to model medical expenditures. RESULTS: Of 19,227 patients, 856 initiated omalizumab, 6,926 initiated HICS, and 11,445 initiated HDICS. Use of ß-agonist increased for the HDICS and HICS cohorts and decreased for the omalizumab cohort; acute care visits and oral corticosteroid use decreased during follow-up for the HDICS and omalizumab cohorts. Annual health care expenditures, polypharmacy burden, and outpatient visits were high for all cohorts and increased in the follow-up year (baseline to follow-up; general health care expenditures: omalizumab $14,071 to $34,887, HICS $12,030 to $15,557, HDICS $7,570 to $9,826; annual number of asthma prescriptions: omalizumab 11.74 to 19.46, HICS 7.8 to 12.44, HDICS 5.17 to 9.69; outpatient visits: omalizumab 26.79 to 34.06, HICS 18.78 to 21.37, HDICS 15.06 to 16.64). CONCLUSION: Omalizumab use was associated with improvements in risk and control accompanied by large increases in expenditures per HRU. Patients on HDICS and HICS showed improvements in risk but worsening control and increased expenditures per HRU. Innovations in disease management and available treatment options are needed to more optimally achieve treatment goals.

Cost-effectiveness of omalizumab in severe persistent asthma in Spain: a real-life perspective.

OBJECTIVES: To determine the cost-effectiveness of omalizumab compared with routine clinical practice in the treatment and control of severe persistent asthma. METHODS: Cost-effectiveness analysis using pre- and post-treatment with omalizumab after 10 months of 47 patients diagnosed with uncontrolled severe persistent asthma attended by the Pneumology Service, Hospital Universitario Virgen de la Victoria, Malaga. Effectiveness was assessed by the number of emergency room (ER) visits for exacerbations and quality-adjusted life years (QALY) gained. The costs of treatment with omalizumab and ER visits were analyzed using the National Health System perspective. Results are expressed in cost per QALY gained and cost per ER visit avoided (costs €2012). RESULTS: Exacerbations with ER visits decreased significantly (p < 0.001) after 10 months of omalizumab treatment compared with the previous 10 months [7.94 (6.52-9.37) vs 0.19 (0.03-0.35)]. Health utilities increased significantly (p < 0.001) during the same period [0.5967 (0.5722-0.6212) vs 0.7566 (0.7232-0.7900)], representing 0.1333 (0.1053-0.1612) QALYs gained (p < 0.001).The mean cost per patient was €1850.78 (1519.46-2182.10) in the 10 months before treatment and €5431.87 (4930.72-5933.02) after 10 months of omalizumab treatment. The incremental cost-effectiveness ratios (ICERs) were €462.08/exacerbation avoided (347.65-606.22) and €26 864.89/QALY gained (21 632.07-33 859.49). CONCLUSIONS: Our results confirm that adding omalizumab to the treatment of patients with uncontrolled severe persistent asthma reduces the number of exacerbations with ER visits and increases health-related quality of life after 10 months of treatment and produces ICERs favorable to omalizumab and acceptable from the health system perspective.

Optimizing the position and use of omalizumab for severe persistent allergic asthma using cost-effectiveness analysis.

BACKGROUND: There has been some controversy on whether the costs of omalizumab outweigh its benefits for severe persistent allergic asthma. OBJECTIVES: This study aimed to resolve the uncertainties and limitations of previous analyses and establish the cost-effectiveness of omalizumab under the list price and Patient Access Scheme (PAS) discounted price for the UK National Health Service. METHODS: A decision-analytic model was developed to evaluate the long-term cost-effectiveness of omalizumab under the perspective of the National Health Service. Outcomes were expressed as quality-adjusted life-years (QALYs). Patient subgroups were defined post hoc on the basis of data collected in clinical trials: previous hospitalization, on maintenance oral corticosteroids, and three or more previous exacerbations. RESULTS: The incremental cost-effectiveness ratio varied from £30,109 to £57,557 per QALY gained depending on the population considered using the PAS price; incremental cost-effectiveness ratios were over a third higher using the list price. Omalizumab is likely to be cost-effective at the threshold of £30,000 per QALY gained in the severe subgroups if the improvement in health-related quality of life from omalizumab is mapped from an asthma-specific measure to the EuroQol five-dimensional questionnaire (vs. the EuroQol five-dimensional questionnaire directly collected from patients) or asthma mortality refers to death after hospitalization from asthma (vs. asthma-mortality risk in the community). CONCLUSIONS: Although the cost-effectiveness of omalizumab is more favorable under the PAS price, it represents good value for money only in severe subgroups and under optimistic assumptions regarding asthma mortality and improvement in health-related quality of life. For these reasons, omalizumab should be carefully targeted to ensure value for money.

An overview of the effects of anti-IgE therapies.

Omalizumab, a humanized mAb that binds to the CH3 domain near the binding site for the high-affinity type-I IgE Fc receptors of human IgE, can neutralize free IgE and inhibit the IgE allergic pathway without sensitizing mast cells and basophils. We found that omalizumab in patients with severe persistent asthma (SPA) was an effective therapy for asthma and the following co-morbid conditions: chronic urticaria (CU), bee venom allergy, latex allergy, atopic dermatitis, food allergy and Samter's syndrome. Information on the use of omalizumab in treatment of asthma and other allergic diseases has improved our understanding that treatment acts on many levels, including regulating levels of inflammatory proteins, including cytokines (copper-containing alpha- 2-glycoprotein, total antioxidant capacity, MDA, NO, H2O2, CXCL8, IL-10, TGF-ß, GMCSF, IL-17, IL-1ß), MPV, Hs-CRP, eosinophil cationic peptide, vitamin-D (25(OH)D), homocysteine (Hcy), OX-2, d- dimer, albumin, and sApo-2L. The decrease in Hcy concentrations and increase in 25(OH)D also support the existence of a vascular endothelial protection mechanism. Mediators and cells classically involved in pro-coagulant and anticoagulant pathways together play a role in SPA and CU pathophysiology and omalizumab effect. The mechanism of action of omalizumab in the treatment of asthma is believed to be multifactorial, and includes effects mediated through altered production of redox metabolites, extrinsic coagulation pathway, oxidative markers-related mi RNA, TRAIL-related mi RNA, and regulation of production of known inflammatory proteins.

The "e" in cost-effectiveness analyses. A case study of omalizumab efficacy and effectiveness for cost-effectiveness analysis evidence.

This article is a call for increased use of real-world evidence in health technology assessment and related policy and decision making. There is currently a disconnect between evidence used to guide regulatory approval of therapies and evidence used to inform therapeutic coverage and reimbursement decisions. Public and private payers need to understand not only whether an intervention works but also whether it offers good value compared with licensed alternatives (not placebo) as they are used in the real-world practice and population (not in a controlled trial environment). Addressing such concerns requires evidence to be drawn from a wide range of study designs, but with consideration and weighting given to their relative strengths and weaknesses, as well as their position on the pragmatic-explanatory (i.e., effectiveness-efficacy) continuum. The potential impact of using different types of evidence to inform cost-effectiveness analysis (CEA) is discussed for omalizumab, comparing and contrasting a CEA model informed by an omalizumab efficacy trial to a CEA model drawing primarily on evidence from effectiveness observational studies of omalizumab. There was reasonable agreement between the two omalizumab CEA models, although the incremental cost-effectiveness ratio generated by the effectiveness observational study-driven model was more favorable for omalizumab. Health technology assessment bodies and payers must use their judgment to determine which components of efficacy-based and effectiveness-based CEA evidence are most closely aligned with their goals. For each CEA evidence component, perhaps the two E's form bounds of the truth as well as a fuller picture of the uncertainty surrounding the truth.

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.

Omalizumab for the treatment of severe persistent allergic asthma: a systematic review and economic evaluation.

BACKGROUND: Allergic asthma is a long-term disorder of the airways resulting from overexpression of immunoglobulin E (IgE) in response to environmental allergens. Patients with poorly controlled asthma are at high risk of exacerbations requiring additional treatment, including hospitalisations. Severe exacerbations are potentially life threatening. Guidelines identify five treatment steps for both adults and children. Omalizumab (Xolair(®)) is a recombinant DNA-derived humanised monoclonal antibody indicated as an add-on therapy in patients aged ≥ 6 years with severe persistent allergic asthma uncontrolled at treatment step 4 or 5. OBJECTIVE: To determine the clinical effectiveness, safety and cost-effectiveness of omalizumab, as an add-on therapy to standard care, within its licensed indication, compared with standard therapy alone for the treatment of severe persistent allergic asthma in adults and adolescents aged ≥ 12 years and children aged 6-11 years. DATA SOURCES: Eleven electronic databases (including MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials) and additional sources including regulatory agency reports were searched from inception to October 2011. Additional data sources include: the manufacturer's submission (MS); two previous National Institute for Health and Care Excellence (NICE) single technology appraisal (STA) submissions; and existing reviews on the safety of omalizumab and oral corticosteroids (OCSs). REVIEW METHODS: Systematic reviews of the clinical effectiveness and cost-effectiveness evidence for omalizumab were performed. The primary outcome was number of clinically significant (CS) exacerbations. Other outcomes included asthma symptoms, unscheduled health-care use, asthma-related mortality, OCS use and health-related quality of life (HRQoL). Because of methodological and clinical heterogeneity between trials, a narrative synthesis was applied. Pragmatic reviews with best evidence syntheses were used to assess adverse events of omalizumab and OCSs. The cost-effectiveness of omalizumab was assessed from the perspective of the UK NHS in the two separate populations: adults and adolescents, and children, using a cohort Markov model. Costs and outcomes were discounted at 3.5% per annum. Results are presented for additional subgroup populations: (1) hospitalised for asthma in the previous year, (2) adults and adolescents on maintenance OCSs and (3) three or more exacerbations in the previous year. RESULTS: Eleven randomised controlled trials (RCTs) and 13 observational studies were identified, including four RCTs/subgroups in the adult licensed population and one subgroup in children. A minority of patients were on maintenance OCSs. No evidence comparing omalizumab with OCSs was identified. Omalizumab significantly reduced the incidence of CS exacerbations in both adults and children [adults: INvestigatioN of Omalizumab in seVere Asthma Trial (INNOVATE): rate ratio 0.74; 95% CI 0.55 to 1.00; children IA-05 EUP (the a priori subgroup of patients who met the European Medicines Agency license criteria) 0.66; 95% CI 0.44 to 1.00]. Significant benefits were observed for a range of other outcomes in adults. Subgroup evidence showed benefits in adults on maintenance OCSs. Evidence for an OCS-sparing effect of omalizumab was limited but consistent. Omalizumab is available as 75 mg and 150 mg prefilled syringes at prices of £128.07 and £256.15 respectively. The incremental cost-effectiveness ratio (ICER) for adults and adolescents is £83,822 per quality-adjusted life-year (QALY) gained, whereas the ICER for children is £78,009 per QALY gained. The results are similar for the subgroup population of ≥ 3 exacerbations in the previous year, whereas the ICER for the other subgroup populations are lower; £46,431 for the hospitalisation subgroup in adults and adolescents, £44,142 for the hospitalisation subgroup in children and £50,181 for the maintenance OCS subgroup. CONCLUSION: Omalizumab reduces the incidence of CS exacerbations in adults and children, with benefits on other outcomes in adults. Limited, underpowered subgroup evidence exists that omalizumab reduces exacerbations and OCS requirements in adults on OCSs. Evidence in children is weaker and more uncertain. The ICERs are above conventional NHS thresholds of cost-effectiveness. The key drivers of cost-effectiveness are asthma-related mortality risk and, to a lesser extent, HRQoL improvement and OCS-related adverse effects. An adequately powered double-blind RCT in both adults and children on maintenance OCSs and an individual patient data meta-analysis of existing trials should be considered. A registry of all patients on omalizumab should be established. STUDY REGISTRATION: The study was registered as PROSPERO CRD42011001625. FUNDING: This report was commissioned by the National Institute for Health Research Health Technology Assessment programme on behalf of NICE as project number HTA 10/128/01.

Cost-effectiveness of omalizumab for uncontrolled allergic asthma in the Netherlands.

BACKGROUND: Omalizumab, licensed for patients with uncontrolled persistent allergic (IgE mediated) asthma, was found to be cost-effective based upon its clinical trial data. Observational studies have been undertaken to determine the real life outcomes of using omalizumab in the community. OBJECTIVE: To determine the cost-effectiveness of omalizumab based upon observational data from the Netherlands and compare to its cost-effectiveness using clinical trial data. METHODS: An observational study (eXpeRience) recruited allergic asthma patients eligible for Omalizumab therapy and followed them while on treatment. At 1 year, data from the Dutch patients enrolled in eXpeRience were examined to estimate the number of exacerbations and resource use while on omalizumab therapy compared to the year prior to omalizumab use. Observational data were used in a Markov model to calculate the lifetime cost-effectiveness ratios. RESULTS: In the 1 year prior to omalizumab therapy the per-person rate of exacerbations was 3.39 compared to 1.07 in the year taking omalizumab. The discounted incremental lifetime additional costs for omalizumab were €55,865 for 1.46 additional quality-adjusted life years (QALY), resulting in €38,371/QALY. Using the INNOVATE clinical trial outcomes and current resource use, the prior ratio was €34,911/QALY, similar to the observational ratio. As in all observational studies, the main limitation is obtaining complete and accurate data. Patients with missing exacerbation or response data were excluded from this analysis. CONCLUSION: Non-clinical trial experience with omalizumab supported the finding of fewer exacerbations in the allergic asthma population while treated with omalizumab, and therapy was found to continue to have an attractive cost-effectiveness ratio.

Omalizumab for the treatment of severe persistent allergic asthma in children aged 6-11 years: a NICE single technology appraisal.

Following a licence extension to include those aged 6-11 years, the National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of omalizumab (Novartis Pharmaceuticals UK) to submit evidence for the clinical and cost effectiveness of this drug for patients with severe persistent allergic asthma in this age bracket. NICE had previously considered the use of omalizumab in patients aged 12 years and over. The Centre for Reviews and Dissemination (CRD) and the Centre for Health Economics (CHE) at the University of York were commissioned as the Evidence Review Group (ERG) to critically appraise the evidence presented by the manufacturer. This article summarizes that review of the evidence, the deliberations of the NICE Appraisal Committee and the resulting NICE guidance. The ERG critically reviewed the evidence presented in the manufacturer's submission and identified areas requiring clarification, for which the manufacturer provided additional evidence. The relevant patient population was patients aged 6-11 years of age with severe persistent allergic immunoglobulin E-mediated asthma whose condition remained uncontrolled despite best standard care with high-dose inhaled corticosteroids and a long-acting inhaled ß2-agonist. The main clinical effectiveness data were derived from a pre-planned subgroup analysis of a single randomized controlled trial comparing omalizumab plus standard therapy against standard therapy alone. At a 52-week follow-up, the only outcome to show a statistically significant benefit of omalizumab compared with placebo was the number of exacerbations defined as 'clinically significant' [CS] (relative risk [RR] 0.504; 95% CI 0.350, 0.725; p < 0.001). At the ERG's request, the manufacturer provided analyses stratified by baseline exacerbation rate, which indicated the effect of omalizumab on CS exacerbations was statistically significant only for those children with ≥3 exacerbations as baseline. The ERG identified a number of issues relating to the clinical effectiveness results: it was unclear whether the pre-planned subgroup analysis had sufficient power; the definition of CS exacerbation was less severe than that used in UK clinical practice; and the method for imputing exacerbations for those who withdrew from treatment may have underestimated the exacerbation rate. The incremental cost-effectiveness ratio based on the manufacturer's results was considerably above the threshold range stated in the NICE Guide to the Methods of Technology Appraisal. The ERG identified numerous issues relating to the cost-effectiveness results, which included the following: the 10-year time horizon for treatment may exceed that in clinical practice; the assumption of constant exacerbation rates over a lifetime given that adolescence is expected to impact on the severity of asthma; and whether it is appropriate to use health-related quality-of-life data collected in adults for children. The ERG concluded that omalizumab appears to reduce CS exacerbations but there was no evidence of improvement in daily symptoms, CS severe (CSS) exacerbations or hospitalization rates. The main driver of cost effectiveness was the reduction in asthma-related mortality associated with a reduction in CSS exacerbations. As the number of CSS exacerbations avoided was low, as is asthma-related mortality in children, the potential small gain in QALYs associated with omalizumab was not sufficient to compensate for the high treatment cost even under the most favourable scenario analyses. The Appraisal Committee recommended that omalizumab should not be routinely provided for the treatment of severe persistent allergic asthma in children aged 6-11 years.

A 36-month study on the cost/utility of add-on omalizumab in persistent difficult-to-treat atopic asthma in Italy.

OBJECTIVE: Omalizumab is a biological treatment for difficult-to-treat allergic asthma. Its mechanism of action relies on impeding the binding of immunoglobulin E (IgE) to specific cellular receptors, thus blocking the inflammatory cascade. At present, no long-term data are available on its cost/effectiveness. The aim of this study is to assess long-term clinical outcomes and to measure the cost/utility of long-term omalizumab use in difficult-to-treat allergic asthmatics. METHODS: The clinical, economic, and quality-of-life (QoL) outcomes of 36-month add-on omalizumab therapy were compared to equivalent outcomes for the year before the therapy's introduction in a cohort (n = 16) of adults with severe uncontrolled atopic asthma on chronic high-dose antiasthma treatments. The variables considered were lung function, IgE levels, health status, Asthma Control Test (ACT) score, QoL (St. George Questionnaire), general practitioner (GP) and specialist visits, number and duration of hospitalizations, emergency room admission, and pharmacological treatment (both dose and duration). Derived calculated indicators were changes in health-related QoL, total healthcare costs, and incremental cost/utility. Data from the two periods were tested for statistically significant differences according to Student's t test and p < .05 was accepted. RESULTS: Add-on omalizumab significantly and progressively improved asthma control and patient health-related QoL. Symptomatic drug and hospital care costs for these patients dropped significantly. A €450 increase in overall monthly costs was observed; however, when health benefits were considered, this cost increase translated into an incremental cost/utility ratio of €23,880 per quality-adjusted life year gained, which is quite a favorable and convenient figure in terms of the willingness to pay for health benefits in industrialized countries. CONCLUSIONS: The 36-month add-on omalizumab therapy persistently improved all clinical outcomes in difficult-to-treat asthmatic patients. Costs were also optimized and related to the extent of long-term health benefits achieved.

Impact of omalizumab on emergency-department visits, hospitalizations, and corticosteroid use among patients with uncontrolled asthma.

BACKGROUND: Omalizumab is a monoclonal antibody indicated for moderate to severe allergic asthma patients with inadequately controlled symptoms. OBJECTIVE: To evaluate the impact of omalizumab on emergency department (ED) visits, hospitalizations, and corticosteroid use among patients with uncontrolled asthma using high-dose inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA). METHODS: Health insurance claims from the MarketScan database (2002Q1-2009Q1) were analyzed. Patients with 12 months or more of continuous insurance coverage before and after the first omalizumab dispensing, 8 or more weeks of high-dose ICS use, 8 or more weeks of LABA use, and uncontrolled asthma at baseline were included. A retrospective analysis was conducted to quantify the impact of omalizumab on resource use by comparing ED visits, hospitalizations, and corticosteroid use 1 year before and after omalizumab initiation. A 1-year period was chosen to cover any potential seasonality impacts. RESULTS: In total, 644 patients (mean age, 49.9; female, 59.2%) formed the study population. Omalizumab was associated with a 48.6% reduction in the proportion of patients with 1 or more asthma-related ED visits (pre vs post-omalizumab period: 21.4% vs 11.0%; P < .001) and a 40.8% reduction in asthma-related hospitalizations (25.0% vs 14.8%, respectively, P < .001). Compared with the pre-omalizumab period, the use of ICS decreased significantly after omalizumab initiation (7.8 vs 6.5 dispensings, P < .001; 41.9% of patients had a reduction in ICS use). A similar reduction in oral corticosteroid use was observed (5.0 vs 3.6 dispensings, P < .001; 53.3% of patients had a reduction in oral corticosteroid use). CONCLUSION: The current analysis showed that omalizumab treatment initiation was associated with significant reductions in ED visits, hospitalizations, and corticosteroid use.

Clinical and pharmacoeconomic aspects of omalizumab: a 4-year follow-up.

OBJECTIVES: The aim of this study was to assess the stability of the effectiveness of omalizumab as add-on treatment in 11 patients with severe persistent allergic asthma followed for 4 years. Secondary outcomes were safety and economic impact, in terms of use of healthcare resources. METHODS: This retrospective study was designed to analyse a series of patients with severe allergic asthma treated with omalizumab. Patients were initially enrolled as part of the CIGE025A2425 international multicentre clinical trial. At the end (week 32), 11 responsive patients went on to complete the study and continued omalizumab treatment until June 2010. The monitoring visits coincided with the timescales planned for administering the drug and for the follow up. To estimate the economic impact, the PRE-POST treatment comparison was obtained by comparing the annual pretreatment costs with an annual average of the 4-year posttreatment period costs RESULTS: After 4 years, 81.8% of patients showed a good/excellent Global Evaluation of Treatment Effectiveness scale score and 81.2% showed an excellent increase (>1.5) in the Asthma Quality of Life Questionnaire score. The average forced expiratory volume in one second (FEV(1)) at 4 years was 75.3% compared with the predicted normal value for each patient, with a net increase (p = 0.009) compared with baseline FEV(1) values (58.6%). The frequency of serious exacerbations dropped by 94.7% compared with the pretreatment period, while mild-moderate exacerbations fell by 41.8%. A reduction in costs was observed for hospital admissions (97.3%), visits to emergency department (ED) (97.5%) and mild-moderate exacerbations (84%). The average cost reduction of concomitant drugs remained at 36%. CONCLUSIONS: This study confirms the effectiveness and reliability of omalizumab over the long term, while providing an excellent safety profile. The additional cost due the use of omalizumab was offset by the medium- and long-term savings associated with the reduction in hospital admissions and access to ED.

Omalizumab for the treatment of severe persistent allergic asthma in children aged 6-11 years.

This paper presents a summary of the evidence review group report into the clinical effectiveness and cost-effectiveness of omalizumab for the treatment of severe persistent asthma in children aged 6-11 years, based upon the evidence submission from Novartis Pharmaceutical UK Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The manufacturer's submission was generally considered to be of good quality. The submission was based primarily on a preplanned subgroup IA-05 EUP (European Union Population) from the IA-05 trial, with outcomes including the number of clinically significant (CS) and clinically significant severe (CSS) exacerbations. Omalizumab therapy was associated with a statistically significant reduction in the rate of CS exacerbations, but the reduction in the rate of CSS exacerbations was not statistically significant. The benefit in terms of CS exacerbations was achieved mainly in patients with more than three exacerbations per year at baseline. The manufacturer found no previous published cost-effectiveness studies of omalizumab in children aged 6-11 years, so their de novo economic evaluation formed the basis of the submitted economic evidence. The economic model was considered appropriate for the decision problem. The results from the model indicated that omalizumab in addition to standard therapy compared with standard therapy alone did not appear cost-effective in either the overall population or a subgroup of patients hospitalised in the year prior to enrollment, with incremental cost-effectiveness ratios of £ 91,169 and £ 65,911 per quality-adjusted life-year, respectively. These findings were found to be robust across a wide range of alternative assumptions through one-way sensitivity analyses. The guidance issued by NICE states that omalizumab is not recommended for the treatment of severe persistent allergic asthma in children aged 6-11 years.

The costs and consequences of omalizumab in uncontrolled asthma from a USA payer perspective.

BACKGROUND: Omalizumab, an anti-immunoglobulin E antibody, reduces exacerbations and symptoms in uncontrolled allergic asthma. The study objective was to estimate the costs and consequences of omalizumab compared to usual care from a US payer perspective. METHODS: We estimated payer costs, quality-adjusted survival (QALYs), and the incremental cost-effectiveness ratio (ICER) of omalizumab compared to usual care using a state-transition simulation model that included sensitivity analyses. Every 2 weeks, patients could transition between chronic asthma and exacerbation health states. The best available evidence informed the clinical and cost input estimates. Five years of omalizumab treatment followed by usual care was assumed to estimate a lifetime horizon. Omalizumab responders (60.5% of treated) were modeled as a separate scenario where nonresponders reverted back to usual care after 16 weeks of active treatment. RESULTS: The mean lifetime discounted costs and QALYs were $83,400 and 13.87 for usual care and $174,500 and 14.19 for omalizumab plus usual care resulting in $287 200/QALY (95% interval: $219,300, $557, 900). The ICER was $172 300/QALY when comparing omalizumab to usual care in the responder scenario. One-way sensitivity analyses indicated that the results were sensitive to the difference in treatment-specific utilities for the chronic state, exacerbation-associated mortality, omalizumab price, exacerbation rates, and response definition. CONCLUSIONS: The results suggest that adding omalizumab to usual care improves QALYs at an increase in direct medical costs. The cost-effectiveness of omalizumab is similar to other chronic disease biologics. The value increases when omalizumab response is used to guide long-term treatment.

The economic value of anti-IgE in severe persistent, IgE-mediated (allergic) asthma patients: adaptation of INNOVATE to Sweden.

BACKGROUND: Severe allergic asthma patients may not be controlled even with guideline recommended care, including inhaled corticosteroids, long-acting beta-2 agonists, theophylline, oral steroids and anti-leukotrienes. They experience exacerbations requiring intensive healthcare use and which may be fatal. Omalizumab, a new monoclonal antibody for use in IgE-mediated allergic diseases, reduces exacerbations and daily symptoms in this patient population. The aim of this study is to estimate the cost effectiveness of adding omalizumab to optimized standard therapy (ST) in patients with severe persistent IgE-mediated (allergic) asthma. METHODS: A Markov model comparing lifelong ST with a treatment period of omalizumab add-on therapy followed by ST, was developed based on efficacy data from the INNOVATE trial (28 weeks, N = 419) and Swedish life table and cost data. This model assumes that patients are at risk of having an exacerbation every 2 weeks and are at risk of dying from a clinically significant severe asthma exacerbation. Patients in a steady-state of having no exacerbations are defined to be in an 'optimized asthma control' state. Resource use data and utilities were obtained from INNOVATE and from a UK observational study. Costs from a societal perspective include estimates for drugs, routine care, exacerbations and costs in added years of life; benefits are expressed in QALYs. The response to omalizumab was evaluated after 16 weeks of trial, and non-responders stopped taking omalizumab for the remaining time. RESULTS: Total lifetime discounted costs and QALYs on ST were 52,702 euros and 11.60. Omalizumab add-on therapy cost an additional 42,754 euros for 0.76 additional QALYs, resulting in an incremental cost-effectiveness ratio of 56,091 euros. A probabilistic sensitivity analysis indicates that the 95% CI around the ICER is [31,328 euros; 120,552 euros]. One-way analyses indicate that the results are sensitive to the exacerbation-related mortality rate, the time horizon and the discount rates. CONCLUSIONS: Based on the model and the assumptions used, our results suggest that omalizumab provides cost offsets, improves quality of life and may have an attractive ICER in treating the severe allergic asthma population.

The role of omalizumab in the treatment of severe allergic asthma.

BACKGROUND: A novel anti-immunoglobulin E (anti-IgE) therapy for asthma, omalizumab, has been approved for use in Canada. OBJECTIVE: To review the basic and clinical data for omalizumab, and to examine its possible role for asthma management in Canada. METHODS: A literature search from 1960 to 2006 was conducted in MEDLINE to identify studies of omalizumab. In addition, abstracts from recent respiratory and allergy scientific meetings were sought, and any unpublished data were requested from the manufacturer. A consensus panel of respiratory and allergy specialists reviewed and summarized the data, and derived a set of recommendations for omalizumab use. RESULTS: Omalizumab is a humanized monoclonal antibody designed to bind to the C epsilon 3 domain of the IgE molecule, forming soluble immune complexes that are cleared by the reticuloendothelial system. Subcutaneous injections, given at two- or four-week intervals at the recommended dose, result in a rapid decrease in free circulating IgE levels. In two phase III clinical trials of 1405 adult and adolescent patients with moderate to severe asthma maintained on moderate doses of inhaled corticosteroids (ICS), omalizumab reduced exacerbation rates compared with placebo, and was associated with improved symptoms and a greater corticosteroid-sparing effect. In a trial of 419 patients with severe disease that was uncontrolled despite the use of high-dose ICS and concurrent long-acting beta2-agonists, severe exacerbations were 50% less frequent in omalizumab-treated patients than in control subjects. Retrospective analyses have identified the characteristics of patients most likely to respond to omalizumab treatment. RECOMMENDATIONS: Omalizumab may be considered as a potential adjunctive therapy in atopic patients with severe asthma uncontrolled by conventional therapy with optimal doses of ICS and appropriate adjunctive therapy (eg, long-acting beta2-agonists). Typically, patients are identified by the need for frequent short course or continuous oral corticosteroids. Therapy should be initiated only after review by a specialist to confirm the diagnosis and that conventional therapy is optimal.