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.     

Modeling the effects of omalizumab over 5 years among patients with moderate-to-severe persistent allergic asthma

Abstract

Objective:

Omalizumab is a monoclonal antibody indicated for adults and adolescents with moderate-to-severe persistent allergic asthma whose symptoms are inadequately controlled with inhaled corticosteroids. Omalizumab has been demonstrated to improve health outcomes of asthmatic patients as compared to placebo. However, to date, the trials conducted have been relatively short (less than 1 year) and have been restricted to a limited set of patients who met the clinical study criteria. This study examined the expected effects of omalizumab over 5 years on a representative sample of all patients eligible for omalizumab in the US.     

Improvement in quality of life with omalizumab in patients with severe allergic asthma

ABSTRACT

Background: Patients with severe persistent asthma experience daily symptoms and frequent serious exacerbations that contribute to a significant impairment of health-related quality of life (QoL).

Methods: A pooled analysis was completed of six controlled clinical trials that evaluated the effect of add-on omalizumab on asthma-related QoL in patients with severe persistent allergic (IgE-mediated) asthma. Asthma-related QoL was assessed at baseline and treatment endpoint using the well-validated Juniper Asthma Quality of Life Questionnaire (AQLQ). Change from baseline in AQLQ total score was compared between treatments using analysis of covariance methods. The percentage of patients who achieved a clinically meaningful (≥ 0.5-point) improvement in AQLQ total score was compared using the Mantel–Haenszel Chi-square test.

Results: The pooled patient population comprised 2548 patients (omalizumab, n = 1342; control, n = 1206), of whom 96% had severe persistent asthma according to the GINA 2002 classification. Omalizumab produced significantly greater improvements in AQLQ total score vs the control group (mean increases of 1.01 and 0.61 points, respectively; p < 0.001). In addition, significantly more omalizumab-treated patients achieved a clinically meaningful improvement in AQLQ total score than patients in the control group (66.3% vs 52.4%; p < 0.001).

Conclusions: Add-on therapy with omalizumab improves QoL to a significant and clinically meaningful level in patients with severe persistent allergic asthma.     

Oral corticosteroid sparing with omalizumab in severe allergic (IgE-mediated) asthma patients

Abstract

Background:

Long-term oral corticosteroid (OCS) therapy and related adverse events are associated with a significant burden on patients and healthcare resources.     

Effect of omalizumab on the need for rescue systemic corticosteroid treatment in patients with moderate-to-severe persistent IgE-mediated allergic asthma: a pooled analysis

ABSTRACT

Background: Allergic asthma is an immunoglobulin E (IgE)-mediated disease characterized by frequent exacerbations following exposure to relevant allergens that leads to the development of chronic airway inflammation. Omalizumab, an anti-IgE antibody, reduces asthma exacerbation and hospitalization rates in patients with IgE-mediated allergic asthma. We investigated the effect of omalizumab on asthma outcomes in a retrospective pooled analysis of data from phase III clinical trials in patients (≥ 12 years) with moderate-to-severe persistent IgE-mediated allergic asthma.

Methods: Systemic corticosteroid bursts and physician and patient overall assessments of asthma control were assessed in patients who received add-on omalizumab or current asthma therapy (control). The association of physician and patient overall assessments with the number of steroid bursts were also evaluated.

Results: The analysis encompassed 4308 patients with moderate-to-severe persistent IgE-mediated allergic asthma (93% met GINA 2002 criteria for severe persistent asthma) from seven clinical trials. The number of systemic corticosteroid bursts was significantly lower in omalizumab-treated patients than in the control group (relative risk [95% CI]: 0.57 [0.48–0.66], p < 0.001). In addition, 58.5% of omalizumab recipients had complete/marked improvement in asthma control according to the physician's overall assessment (responders) vs. 36.9% in the control group (?p < 0.001). Similarly, 64.2% of omalizumab patients vs. 43.9% of control patients had complete/marked improvement according to the patient's overall assessment (?p < 0.001). There were statistically significant associations between systemic corticosteroid bursts and physician (Goodman–Kruskal gamma [95% CI]: 0.32 [0.26–0.38]) and patient (gamma [95% CI]: 0.29 [0.23–0.36]) overall assessments. This pooled analysis has limitations as it was not pre-specified.

Conclusions: Omalizumab therapy reduced the need for systemic corticosteroid bursts and improved effectiveness of asthma treatment as judged by both physicians and patients.     

In the strategies to prevent asthma exacerbations,allergic asthma needs specific treatment

No generally accepted definition of asthma exacerbation is thus far available, though in 2012 an expert committee endorsed by the National Institute of Health proposed such definition as “a worsening of asthma requiring the use of systemic corticosteroids to prevent a serious outcome”. Graham and Eid reviewed the impact of asthma exacerbations, and noted that, analysing the outcomes with existing treatments, many patients with asthma remain symptomatic and experience exacerbations. This requires the introduction of new strategies to more effectively reduce the exacerbation risk, based on correct diagnosis, stopping smoking, correct inhaler technique, consistent adherence, weight management, and gaining control with the addition of medication”. Indeed, as allergic asthma is the most common form, a specific approach by allergen immunotherapy should receive more attention. Actually, the efficacy of immunotherapy in allergic asthma, by the subcutaneous or the sublingual route, is supported by robust meta-analyses. The most important allergen source causing asthma is the house dust mite, but an increasing role for molds is apparent due to the ongoing climate change.     

Efficacy of Omalizumab,an Anti-immunoglobulin E Antibody,in Patients with Allergic Asthma at High Risk of Serious Asthma-related Morbidity and Mortality

Summary

Aim: Add-on therapy with omalizumab, an anti-immunoglobulin E antibody, is effective in improving disease control in patients with allergic asthma of varying severity. The aim of the present study was to determine the efficacy of omalizumab in a subgroup of patients at high risk of serious asthma-related morbidity and mortality.

Methods: A meta-analysis was performed of three randomised, double-blind, placebo-controlled studies (studies 1, 2 and 3) that enrolled 1412 patients with moderate or severe allergic asthma, all requiring daily treatment with inhaled corticosteroids (ICS). Omalizumab was administered subcutaneously every 2 or 4 weeks at a total 4-weekly dose of at least 0.016mg/kg/IgE [IU/ml]. Each study consisted of a 16-week steroid-stable phase and a 12-16-week steroid-reduction phase, followed by a 24-week extension phase (studies 1 and 2 only). The primary outcome measure was the annualised rate of significant asthma exacerbation episodes (sAEEs) during the steroid-stable phase for the pooled subgroup of 254 high-risk patients (omalizumab, n?=?135; placebo, n?=?119). sAEEs were those requiring a doubling of baseline ICS dose (studies 1 and 2 only) or use of systemic steroids (all three studies).

Results: Overall, the number of patients with at least one sAEE during the steroid-stable phase was reduced from 35% (42/119) with placebo to 18% (24/135) with omalizumab. Mean sAEE rates were 1.56 and 0.69 per patient-year, respectively, a reduction of 56% with omalizumab (p?=?0.007). Similar reductions in exacerbations in favour of omalizumab were observed for the whole study period and for all AEEs. In those with a history of hospitalisation in the last year, 6/49 (12%) on placebo vs. 2/44 (4.5%) on omalizumab were re-hospitalised during the study period. Patients treated with omalizumab also showed significantly greater improvements from baseline in PEFR (p?=?0.026), overall AQoL (p?=?0.042) and mean nocturnal (p?=?0.007) and mean total (p?=?0.011) asthma symptom scores compared with placebo.

Conclusions: In patients at high risk of serious asthma-related morbidity and mortality, treatment with omalizumab offers the potential to halve the rate of asthma exacerbations and improve disease control.     

急性危重型哮喘抢救的经验及教训(附39例报告)

目的：本文旨在探索急性危重型哮喘抢救的经验及教训。方法：观察并分析了３９例住院患者。结果：抢救成功３５例，成功率８９７％（３５／３９）；死亡４例，占同期住院哮喘患者的５１３％（４／８４）。结论：及时正确地评估病情，合理应用糖皮质激素等药物，适时建立人工通气等均是抢救成败的关键。而血糖浓度的监测对于指导糖皮质激素量的应用有一定的意义。     

Patient and Physician Satisfaction with Rofecoxib in Osteoarthritis: Results of the EVA (Experience with VIOXX in Arthritis) Survey. Current Medical Research and Opinion, 17(2): 81-8, 2001

Abstract

Background:

Several studies have demonstrated the beneficial effects of omalizumab in asthma patients. Here we describe the drug’s tolerance and oral corticosteroid sparing capacity in a long-term observational study.     

Therapeutic treatment with heat-killed Mycobacterium vaccae (SRL172) in a mild and severe mouse model for allergic asthma

The hypothesis that a lack of early childhood bacterial infections would favor the development of allergic disease suggests that bacteria can be used as a potential treatment for allergic asthma. Therefore, in this study, we investigated the therapeutic potential of heat-killed Mycobacterium vaccae in two mouse models of allergic asthma. For this purpose, mice were sensitized i.p. with ovalbumin/alum (severe model) or ovalbumin alone (mild model) and challenged on days 77, 80 and 83 by inhalation of either ovalbumin or saline aerosols. Treatment of mice with M. vaccae (s.c. 10⁷ or 10⁸ colony-forming units) on days 56 and 63, however, did not reduce airway hyperresponsiveness and eosinophilia, IgE and interleukin-5 production 24 h after ovalbumin challenge in either mouse model. We therefore conclude that treatment of sensitized mice with M. vaccae before allergen exposure is not able to reduce the allergic and asthma-like response in a mild and a severe model of allergic asthma.     

Omalizumab decreases IgE production in patients with allergic (IgE-mediated) asthma; PKPD analysis of a biomarker, total IgE

AIMTo determine whether excessive IgE production by patients with atopic allergic asthma decreases with omalizumab therapy.METHODSOmalizumab, free and total IgE data were obtained from an epidemiological study and six randomized, double-blind, placebo-controlled trials in patients with allergic asthma. The binding between omalizumab and IgE together with the production and elimination of IgE were modelled as previously, except that, in order to explain why total IgE was decreasing over a period of 5 years, the expression of IgE was allowed to change.RESULTSThe prior constant IgE production model failed to converge on the data once long-term observations were included, whereas models allowing IgE production to decrease fitted. A feedback model indicated that, on average, IgE production decreased by 54% per year. This model was further developed with covariate searches indicating clinically small but statistically significant effects of age, gender, body mass index and race on some parameters. Model predictions were checked internally and externally against 3–5 year data from paediatric and adult atopic asthmatic patients and externally against extensive total IgE data from a long-duration (>1 year) phase 1 study which was not used in the model building.CONCLUSIONSA pharmacokinetic–pharmacodynamic model incorporating omalizumab–IgE binding and feedback for control of IgE production indicates that omalizumab reduces production of IgE. This raises the possibility that indefinite treatment may not be required, only for perhaps a few years. After the initial accumulation, total IgE should provide a means to monitor IgE production and guide individual treatment decisions.     

哮喘控制测试表在支气管哮喘患者健康教育中应用的意义

目的探讨哮喘控制测试（ACT）量表在支气管哮喘健康教育中应用对控制好坏的影响。方法支气管哮喘患者52例随机分为干预组（A组）和对照组（B组），B组由护理人员在患者住院期间对患者进行简明扼要的健康教育，告知患者哮喘是可以应用正确的方法预防和控制的，尽可能消除患者的焦虑抑郁心理，同时介绍如何规范正确地用药及怎样进行预防发作等知识。患者在病情缓解出院后按支气管哮喘防治指南规范使用沙美特罗替卡松治疗，A组在B组的基础上在患者住院期间向患者讲解ACT量表各项的意义及填写，患者出院后以电话形式进行跟踪随访，每周1次。若患者达不到满意的25分，嘱患者进行自检吸入方法是否正确，若吸入方法不正确则予以告知纠正；若吸入方法正确则说明吸入量不足，嘱患者增加吸人量。治疗2个月后复诊进行肺通气功能检查（第1秒用力呼气量、清晨呼气流速及气道反应性）。结果A组患者FEV。及清晨PEF均比B组患者改善（P〈0．05），A组患者气道反应性比B组患者减轻（P〈0．01）。结论用ACT评价支气管哮喘控制的好坏并以指导患者治疗用药比常规的健康教育指导可使患者肺功能得到较好的改善。     

Impact of asthma controller medications on medical and economic resource utilization in adult asthma patients

Abstract

Objective:

To compare asthma-related resource utilization, adherence and costs among adults prescribed asthma controller regimens.     

甲基强的松龙两种不同用法在成人哮喘重度持续发作中的疗效比较

目的:比较甲基强的松龙两种用法在成人哮喘重度持续发作中的治疗效果.方法:将2010年1月～12月在我院就诊的成人哮喘重度持续发作的患者80例随机分为两组,每组各40例,治疗组采用负荷量(80 mg/8 h)为起始治疗量,对照组采用常规治疗量(40 mg/8 h)为起始治疗量,逐步增加至负荷量.结果:治疗组平均缓解时间为(16±3.5)h,对照组为(27±4.7)h,两组比较差异有统计学意义(P＜0.05).结论:以负荷量为起始治疗量有助于成人哮喘持续发作的快速缓解.     

The cost-effectiveness of treatment with desloratadine in patients with persistent allergic rhinitis

Abstract

Objectives:

A new classification of persistent allergic rhinitis (PER) has been developed by the ARIA working group. Although the burden of AR is significant, treatment itself is also costly. It is unclear if treatment based on the new definition of PER is cost-effective.     

Role of anti-IgE monoclonal antibody (omalizumab) in the treatment of bronchial asthma and allergic respiratory diseases

IgE molecules play a crucial role in allergic respiratory diseases and may cause chronic airway inflammation in asthma through activation of effector cells via high-affinity (FcepsilonRI) or low-affinity (FcepsilonRII) IgE receptors. Since the discovery of IgE antibodies our understanding of the mechanisms of allergy has improved to such an extent that we can differentiate allergic/atopic from intrinsic respiratory diseases. Therapeutic anti-IgE antibodies, able to reduce free IgE levels and to block the binding of IgE to FcepsilonRI without crosslinking IgE and triggering degranulation of IgE-sensitized cells have been developed. This non-anaphylactogenic anti-IgE monoclonal antibody (omalizumab) binds IgE at the same site as these antibodies bind FcepsilonRI and FcepsilonRII. Consequently, omalizumab inhibits IgE effector functions by blocking IgE binding to high-affinity receptors on IgE effector cells and does not cause mast cell or basophil activation because it cannot bind to IgE on cell surfaces where the FcepsilonR1 receptor already masks the anti-IgE epitope. Studies in patients with atopic asthma showed that omalizumab decreases serum IgE levels and allergen-induced bronchoconstriction during both the early and late-phase responses to inhaled allergen. In several clinical controlled trials omalizumab resulted effective in reducing asthma-related symptoms, decreasing corticosteroid use and improving quality of life of asthmatic patients. Recent studies show the benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled by optimal pharmacological therapy. The anti-IgE approach to asthma treatment has several advantages, including concomitant treatment of other IgE-mediated diseases such as allergic rhinitis, a favorable safety profile and a convenient dosing frequency.