Uncontrolled Severe Allergic Asthma Research Articles

Impact of Omalizumab in Patients with Severe Uncontrolled Asthma and Possible Predictive Biomarkers of Response: A Real-Life Study

Most patients with asthma can control their symptoms with a basic standard of medical care and with maintenance and rescue medication. However, between 5% and 10% of asthmatics worldwide do not achieve control of their symptoms and have recurrent exacerbations and respiratory difficulties. The objective of the study was the real-life evaluation of the clinical improvement of patients with severe eosinophilic asthma treated with omalizumab, together with the search for biomarkers associated with the response. An observational retrospective cohort study was conducted that included patients with severe uncontrolled allergic asthma being treated with omalizumab. Three types of response were evaluated: lower use of oral corticosteroids, improvement in lung function, and reduction in exacerbations. A total of 110 patients under treatment with omalizumab were included, with a mean age of 48 ± 16 years. After 12 months had elapsed, significant reductions were found in the number of exacerbations, use of oral cortico-steroids and doses of inhaled corticosteroids (p < 0.001). Lung function and asthma control improved significantly (p < 0.001; p = 0.004) and eosinophil levels were significantly reduced (p = 0.004). Low scores in the Asthma Control Test were associated with the oral corticosteroid-saving effect; lower previous FEV1 levels and absence of chronic obstructive pulmonary disease (COPD) were related to improvement in lung function, and prior FEV1 values higher than 80% and absence of gastroesophageal reflux disease (GERD) with a reduction in exacerbations. The results of this study confirm the clinical benefit obtained after the introduction of omalizumab and the possible predictive biomarkers of response to the treatment.

Real-life Effectiveness of Omalizumab in Patients with Severe Allergic Asthma: RELIEF Study.

Patients with severe allergic asthma (SAA) are at risk of severe exacerbations. Omalizumab is recommended as an add-on treatment for patients with uncontrolled SAA, despite high-dose inhaled corticosteroids and long acting β2-agonist combination therapy (standard therapy).RELIEF was a prospective, open label, multicenter study conducted to assess the real-life effectiveness of omalizumab co-administered with standard therapy in patients with SAA for 24 months. A total of 347 patients aged ≥ 6 years with SAA were enrolled, 285 of whom (8 pediatrics and 277 adolescents and adults) completed this 24-month study. Compared with the 12 months prior to baseline, the mean number of exacerbations was reduced in the overall population at any time interval during the study. Proportion of patients with no exacerbations increased to 77.7% at 24 months from 32.6% at 12 months prior to baseline. A reduction in healthcare resource utilization was also observed. The mean number of specialist visits reduced from baseline (5.8 visits) to 2.4 visits at Month 24. The mean asthma control test score was >19 at every time-point during the study. The rate of Global Evaluation of Treatment Effectiveness (GETE) for asthma response significantly increased at Months 18 and 24 (P <0.05) compared to baseline. Pulmonary function remained relatively stable for the overall study population. There were no new or unexpected safety findings in the study. RELIEF study showed that add-on therapy with omalizumab is effective in reducing exacerbations, healthcare utilization, and improving GETE score in patients with SAA uncontrolled by standard therapy.

Understanding uncontrolled severe allergic asthma by integration of omic and clinical data.

Asthma is a complex, multifactorial disease often linked with sensitization to house dust mites (HDM). There is a subset of patients that does not respond to available treatments, who present a higher number of exacerbations and a worse quality of life. To understand the mechanisms of poor asthma control and disease severity, we aim to elucidate the metabolic and immunologic routes underlying this specific phenotype and the associated clinical features. Eighty-seven patients with a clinical history of asthma were recruited and stratified in 4groups according to their response to treatment: corticosteroid-controlled (ICS), immunotherapy-controlled (IT), biologicals-controlled (BIO) or uncontrolled (UC). Serum samples were analysed by metabolomics and proteomics; and classifiers were built using machine-learning algorithms. Metabolomic analysis showed that ICS and UC groups cluster separately from one another and display the highest number of significantly different metabolites among all comparisons. Metabolite identification and pathway enrichment analysis highlighted increased levels of lysophospholipids related to inflammatory pathways in the UC patients. Likewise, 8 proteins were either upregulated (CCL13, ARG1, IL15 and TNFRSF12A) or downregulated (sCD4, CCL19 and IFNγ) in UC patients compared to ICS, suggesting a significant activation of T cells in these patients. Finally, the machine-learning model built including metabolomic and clinical data was able to classify the patients with an 87.5% accuracy. UC patients display a unique fingerprint characterized by inflammatory-related metabolites and proteins, suggesting a pro-inflammatory environment. Moreover, the integration of clinical and experimental data led to a deeper understanding of the mechanisms underlying UC phenotype.

Omalizumab and modification of bronchial asthma natural course

Clinical and molecular heterogeneity of bronchial asthma has been documented in recent years. The search for novel solutions to enhance efficient patient support related first of all to understanding of asthma heterogenic nature and allows to personalize each patient treatment. Biological therapy application can influence to achieve better control at greater extent for patients with severe uncontrolled asthma. Nowadays 5 biological drugs are registered on Russian Federation territory and implemented according to severe asthma phenotypes: anti-IgE, anti-IL-4,13 and anti-IL-5 class therapies. Omalizumab become the first target drug for uncontrolled allergic asthma patients (monoclonal antibody against IgE). This medication is prescribed for uncontrolled moderate and severe allergic (atopic) asthma in patients on basic asthma therapy according GINA step 4 and 5 (Level of evidence A). Clinical trials confidently reported that anti- IgE-therapy reduces the rate of asthma exacerbations, severity of disease in patients with chronic severe asthma on high doses of inhaled steroids or systemic steroids and allows to reduce or withdraw systemic steroids doses in case of steroid-dependent asthma. For the last years special attention led to and demonstrated omalizumab positive effect on airways remodeling and modification of bronchial asthma natural course in adults and children. Antiinflammatory effect of omalizumab is documented. Omalizumab significantly reduces eosinophilic infiltration of submucosal bronchi layer among patients with atopic asthma, sputum eosinophilia, which correlates with reduction of FeNO during biologic treatment, reduces mast cells infiltration of smooth muscle cells in bronchi. Omalizumab significantly reduces the thickness of the bronchial wall, increases the lumen of the bronchi (positive dynamics of CT-scan parameters), which is clinically manifested by increased of FEV1.

Cost-utility of omalizumab for the treatment of uncontrolled moderate-to-severe persistent pediatric allergic asthma in a middle-income country.

Although several randomized clinical trials performed in children 6 years and older with Omalizumab as add-on therapy have reported improvements in diverse clinical outcomes, the evidence regarding its cost effectiveness is not sufficient, especially in less-affluent countries, where the clinical and economic burden of the disease is the greatest. The aim of the present study was to perform a cost-utility analysis of adding omalizumab to standard treatment for treating pediatric patients with uncontrolled severe allergic asthma in Colombia, a middle-income country (MIC). A Markov-type model was developed to estimate costs and health outcomes of a simulated cohort of pediatric patients with persistent asthma treated over a 5-year period. The effectiveness data and transition probabilities were obtained from various sources, including systematic reviews with meta-analysis. Cost data were obtained from official databases provided by the Colombian Ministry of Health. The study was carried out from the perspective of the national healthcare system in Colombia. The main outcome was the variable ''quality-adjusted life-years'' (QALYs). For the base-case analysis, the cost-utility analysis showed that compared with the standard treatment strategy, the omalizumab strategy involved higher costs (US$72,142.3 vs. $20,243.4 average cost per patient) and greater gain in QALYs (0.8718 vs. 0.8222 QALYs on average per patient). The incremental cost-utility ratio (ICUR) of omalizumab compared with standard treatment was US$82,748.1 per QALY CONCLUSIONS: This study shows that in Colombia, an MIC, compared with standard treatment, omalizumab is not a cost-effective strategy for treating pediatric patients with uncontrolled severe allergic asthma.

TOPIC SESSIONS

TOPIC SESSIONS

Severe asthma: adding new evidence – Latin American Thoracic Society

This document constitutes a summary of the clinical practice guidelines (CPGs) prepared at the initiative of the Latin American Thoracic Society (ALAT). Due to new evidence in the treatment of severe asthma, it was agreed to select six clinical questions, and the corresponding recommendations are provided herein. After considering the quality of the evidence, the balance between desirable and undesirable impacts and the feasibility and acceptance of procedures, the following recommendations were established. 1) We do not recommend the use of an inhaled corticosteroid (ICS) plus formoterol as rescue medication in the treatment of severe asthma. 2) We suggest performing many more high-quality randomised studies to evaluate the efficacy and safety of tiotropium in patients with severe asthma. 3) Omalizumab is recommended in patients with severe uncontrolled allergic asthma with serum IgE levels above 30 IU. 4) Anti-interleukin (IL)-5 drugs are recommended in patients with severe uncontrolled eosinophilic asthma (cut-off values above 150 cells·µL−1 for mepolizumab and above 400 cells·µL−1 for reslizumab). 5) Benralizumab is recommended in adult patients with severe uncontrolled eosinophilic asthma (cut-off values above 300 cells·µL−1). 6) Dupilumab is recommended in adult patients with severe uncontrolled allergic and eosinophilic asthma and in adult patients with severe corticosteroid-dependent asthma.

Effect of individual allergen sensitization on omalizumab treatment outcomes in patients with severe allergic asthma determined using data from the Czech Anti-IgE Registry

BackgroundOmalizumab is an efficient drug for patients with uncontrolled severe allergic asthma (SAA). However, little is known about the differences in omalizumab treatment outcomes among patients with different types of atopic sensitization. Here, we assessed the effect of sensitization to individual allergens or their combinations on the outcomes of anti-IgE therapy in patients with SAA.MethodsWe performed a post hoc analysis of data of subgroups of patients enrolled in the Czech Anti-IgE Registry (CAR). The patients were evaluated at baseline and 16 weeks and 12 months after omalizumab treatment initiation. We analyzed the dependence of primary treatment outcomes [global evaluation of treatment effectiveness (GETE) after 16 weeks of treatment, a reduction in severe exacerbation rate (ER), and an improvement in the asthma control test (ACT) result during 12 months of treatment] and secondary outcomes [a reduction in systemic corticosteroid (SCS) use, an improvement in lung functions, and a fraction of exhaled nitric oxide] of patients with SAA treated with omalizumab for 12 months on sensitization to different perennial aeroallergens. We assessed sensitization to house dust mites, molds, and pets at baseline using skin prick tests and/or specific IgE measurement (semiquantitative evaluation). We compared polysensitized patients (sensitized to all tested allergens) with monosensitized (single positivity) or partially polysensitized patients (combined positivity but not to all allergens).ResultsWe enrolled 279 patients (58.3% women, mean age 52.9 years). Omalizumab treatment presented an 82.8% response rate (according to GETE). It significantly reduced severe asthma exacerbations and SCS use, and improved the ACT result in 161 responders. We identified a subgroup of responders with distinct sensitization patterns (polysensitization to all tested perennial allergens) with higher odds of being responders (OR = 2.217, p = 0.02) and lower tendency to improve ACT result (OR 0.398, p = 0.023) and reduce ER (OR 0.431, p = 0.034) than non-polysensitized patients.ConclusionsThe clinical benefit of sensitization for patients with SAA receiving omalizumab may be particularly dependent on sensitization pattern. Polysensitized patients showed a higher tendency to be responders (GETE), but a lower tendency to improve the ACT result and reduce ER than non-polysensitized patients.

Pragmatic Clinical Perspective on Biologics for Severe Refractory Type 2 Asthma

Patients with severe refractory asthma present a challenging clinical conundrum for practicing clinicians. Biologics that target key mediators in the type 2 inflammation cascade, including IL-4, IL-5, IL-13, and IgE, can be effective strategies for these patients. However, with various biologics available, choosing the optimal one for a particular patient becomes a nuanced decision. We propose a pragmatic algorithm that identifies the optimal biologic class for patients who have specific type 2 disease endotypes. Patients with eosinophilic endotypes fare well with anti-IL-5(rα) medications, comprising mepolizumab, benralizumab, and reslizumab because they have been shown to reduce exacerbations in severe eosinophilic asthma by approximately 50%. In patients with fractional exhaled nitric oxide-high endotypes, anti-IL-4rα such as dupilumab is deemed to be most effective and has demonstrated a 47% reduction in asthma exacerbations. For patients with severe uncontrolled allergic asthma, anti-IgE (omalizumab) is effective and has been shown to confer a 25% reduction in asthma exacerbations. Type 2 comorbidities including chronic rhinosinusitis with nasal polyps, atopic dermatitis, chronic idiopathic urticaria, and eosinophilic esophagitis are important to bear in mind before the prescription of biologics. Further head-to-head studies are indicated to compare biologics in patients with mixed endotypes according to peripheral blood eosinophils, fractional exhaled nitric oxide, and allergic status. The evidence strongly supports endotype-driven prescribing of biologics to achieve clinically relevant outcomes in severe refractory asthma and related comorbidities.

Efficacy and safety of treatment with biologicals (benralizumab, dupilumab and omalizumab) for severe allergic asthma: A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma.

Allergic asthma is a frequent asthma phenotype. Both IgE and type 2 cytokines are increased, with some degree of overlap with other phenotypes. Systematic reviews assessed the efficacy and safety of benralizumab, dupilumab and omalizumab (alphabetical order) vs standard of care for patients with uncontrolled severe allergic asthma. PubMed, Embase and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. All three biologicals reduced with high certainty the annualized asthma exacerbation rate: benralizumab incidence rate ratios (IRR) 0.63 (95% CI 0.50-0.81); dupilumab IRR 0.58 (95%CI 0.47-0.73); and omalizumab IRR 0.56 (95%CI 0.42-0.73). Benralizumab and dupilumab improved asthma control with high certainty and omalizumab with moderate certainty; however, none reached the minimal important difference (MID). Both benralizumab and omalizumab improved QoL with high certainty, but only omalizumab reached the MID. Omalizumab enabled ICS dose reduction with high certainty. Benralizumab and omalizumab showed an increase in drug-related adverse events (AEs) with low to moderate certainty. All three biologicals had moderate certainty for an ICER/QALY value above the willingness to pay threshold. There was high certainty that in children 6-12years old omalizumab decreased the annualized exacerbation rate [IRR 0.57 (95%CI 0.45-0.72)], improved QoL [relative risk 1.43 (95%CI 1.12 -1.83)], reduced ICS [mean difference (MD) -0.45 (95% CI -0.58 to -0.32)] and rescue medication use [ MD -0.41 (95%CI -0.66 to -0.15)].

Omalizumab for Severe Allergic Asthma Treatment in Italy: A Cost-Effectiveness Analysis from PROXIMA Study.

IntroductionInadequately controlled severe asthma patients require additional therapy accounting for significant clinical and economic burden. Our analysis aims to determine the cost-effectiveness of omalizumab in the management of severe allergic asthma in Italy based on observational data from the PROXIMA study.MethodsObservational data on efficacy, healthcare resource utilization and changes in quality of life at 12 months after the initiation of omalizumab were examined to estimate the cost-effectiveness compared to pre-omalizumab period and results were expressed with Incremental Cost-Effectiveness Ratio (ICER). The cost–utility analysis estimated the cost per quality-adjusted life-year (QALY) gained. Direct health costs were assessed from the perspective of the Italian National Health Service (NHS).ResultsOmalizumab reduced the incidence of exacerbations, number of hospitalizations, physician visits, and improved quality of life after 12 months of treatment. Omalizumab had a greater effectiveness than pre-omalizumab treatment involving 0.132 QALYs gained and led to a €3729 per patient reduction in direct healthcare costs, excluding the add-on treatment cost. Nevertheless, the addition of omalizumab cost led to €7478 increase in total direct costs with respect to pre-omalizumab period. Based on difference in total direct cost and difference in QALY between post and pre-omalizumab period, the ICER was €56,847. According to sensitivity analysis, omalizumab provided a cost-effective use of NHS resources, already at 20% discounted price.ConclusionThis study offers a real-world evidence of omalizumab effectiveness in Italy. Despite the high acquisition cost of the innovative drug, omalizumab is a sustainable treatment option for patients with uncontrolled severe allergic asthma.

Real-life effectiveness of omalizumab in difficult-to-treat versus severe asthma: a national cohort study in Belgium.

BackgroundGuidelines recommend omalizumab in patients with uncontrolled severe allergic asthma. We investigated real-life use of omalizumab, the proportion of patients fulfilling eligibility criteria, its costs and its effectiveness.MethodIn a cohort of asthma patients initiating treatment with omalizumab in Belgium between 2010 and 2016, we investigated fulfilment of eligibility criteria (chronic use of high-dose inhaled corticosteroids (ICSs) plus long-acting β2-agonists (LABAs) and ≥2 severe asthma exacerbations in previous year), and compared hospitalisations and systemic corticosteroid consumption in the year before and after omalizumab initiation. We computed healthcare costs in the respective time periods and compared the cost per prevented hospitalisation in patients fulfilling eligibility criteria versus those who did not.ResultsBetween 2010 and 2016, omalizumab treatment was initiated in 2068 patients with asthma; only 24% fulfilled the eligibility criteria, mainly due to nonadherence to high-dose ICSs + LABAs. The proportion of patients hospitalised for asthma decreased from 41% to 21% in eligible patients (absolute risk reduction, 20%), whereas the absolute risk reduction was 5% (from 19% to 14%) in noneligible patients. The cost per prevented hospitalisation was €44 238 versus €139 495, respectively. Chronic use of systemic corticosteroids was discontinued in 35% of eligible patients versus 15% of noneligible patients.ConclusionIn Belgium, omalizumab is mostly initiated in uncontrolled asthma patients who are nonadherent to ICSs + LABAs. Omalizumab decreases hospitalisations and the use of systemic corticosteroids, but at a high cost. Careful management of patients with difficult-to-treat asthma should be a priority before prescribing omalizumab.

Omalizumab in children with severe allergic disease: a case series

BackgroundCurrently, severe allergic asthma and food allergy in children represent an important public health problem with medical, psychosocial and economic impacts. Omalizumab is a humanized monoclonal anti-IgE antibody, approved for refractory allergic asthma and chronic urticaria. It has been widely used in clinical practice as add-on therapy in patients with severe uncontrolled allergic asthma. In recent years there has seen the emergence of an allergic epidemic with increasing food allergy, which represents the main cause of anaphylaxis in children. The standard of care for food allergy is strictly dietary allergen avoidance and emergency treatment, but recent clinical trials have suggested that omalizumab may have a role to play as an adjuvant to oral immunotherapy (OIT). We present a case series of patients treated at our institution with omalizumab for severe allergic asthma and food allergy.MethodsPatients received omalizumab according to a standard reference nomogram after failing standard therapies. In children with comorbid severe food allergy, omalizumab was administered in conjunction with an oral immunotherapy protocol.ResultsOmalizumab was effective in controlling symptoms of allergic asthma, allergic rhinitis and rhinosinusitis, but not eosinophilic esophagitis, while aiding successful oral desensitization of comorbid severe food allergies.ConclusionsOmalizumab appears to be an excellent therapeutic option in children with inadequately controlled severe allergic asthma, allergic rhinitis and rhinosinusitis, with or without food allergy.

Non-eosinophilic asthma: current perspectives.

Although non-eosinophilic asthma (NEA) is not the best known and most prevalent asthma phenotype, its importance cannot be underestimated. NEA is characterized by airway inflammation with the absence of eosinophils, subsequent to activation of non-predominant type 2 immunologic pathways. This phenotype, which possibly includes several not well-defined subphenotypes, is defined by an eosinophil count <2% in sputum. NEA has been associated with environmental and/or host factors, such as smoking cigarettes, pollution, work-related agents, infections, and obesity. These risk factors, alone or in conjunction, can activate specific cellular and molecular pathways leading to non-type 2 inflammation. The most relevant clinical trait of NEA is its poor response to standard asthma treatments, especially to inhaled corticosteroids, leading to a higher severity of disease and to difficult-to-control asthma. Indeed, NEA constitutes about 50% of severe asthma cases. Since most current and forthcoming biologic therapies specifically target type 2 asthma phenotypes, such as uncontrolled severe eosinophilic or allergic asthma, there is a dramatic lack of effective treatments for uncontrolled non-type 2 asthma. Research efforts are now focusing on elucidating the phenotypes underlying the non-type 2 asthma, and several studies are being conducted with new drugs and biologics aiming to develop effective strategies for this type of asthma, and various immunologic pathways are being scrutinized to optimize efficacy and to abolish possible adverse effects.

PRS17 - Omalizumab Is Cost-Effective Compared To Standard of Care in Uncontrolled Severe Allergic Asthma Patients

To systematically review published cost-effectiveness analyses of omalizumab in asthma and to identify drivers of cost-effectiveness. We performed a systematic literature review by searching key biomedical databases (from inception until Jan 2018) by combining asthma, omalizumab and economic key words (limited to English language studies). Two reviewers independently screened the identified studies and extracted data; a third independent reviewer resolved any discrepancies. Drummond checklist was used to assess the quality of studies. A total of 31 studies were included. The studies evaluated add-on omalizumab in patients with severe (87%) or moderate-to-severe (13%) uncontrolled allergic asthma vs standard therapy alone (mostly inhaled corticosteroids [ICS] ± long-acting beta-agonists [LABA]). The included studies covered different geographies: US (5 studies), LaCan (7), EU (14), Asia (5); 35% evaluated cost effectiveness from health-care perspective, 19% each from payer and societal perspective, 25% did not report perspective; 74% of studies used decision-analytic models (time horizon: lifelong/range: 2–30 years). Efficacy data from clinical studies (58%), observational studies (55%; national database, real-world data and patient data from single institution) and literature (19%) were used. In majority of the studies (n=23; 74%), omalizumab was found to be cost-effective vs standard therapy. Of these, 74% (17 of 23) studies reported quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) for omalizumab ranged from US$13,841/QALY to US$67,907/QALY. Overall, 29% (9 of 31) studies reported cost-effectiveness acceptability curves; the probability of omalizumab being cost effective according to local willingness-to-pay thresholds ranged from 50% to 95%. The ICER was most sensitive to cost and duration of omalizumab therapy, discount rate, exacerbations, time horizon, and utility gain. The majority of peer-reviewed cost-effectiveness analysis inferred omalizumab to be a cost effective add-on therapy for patients with severe allergic asthma who are symptomatic despite standard therapy (ICS/LABA).

Real-world effectiveness and safety of omalizumab in patients with uncontrolled severe allergic asthma from the Czech Republic.

IntroductionThis was a sub-group analysis of patients with uncontrolled persistent allergic asthma (AA) in the healthcare setting of the Czech Republic, from a global non-interventional, 2-year post-marketing, observational eXpeRience registry.AimTo evaluate the real-life effectiveness and safety of omalizumab.Material and methodsPatients with uncontrolled persistent AA (currently defined by the Global Initiative for Asthma (GINA) as uncontrolled severe AA) who started omalizumab treatment 15 weeks before inclusion in the registry were analysed for physicians’ global evaluation of treatment effectiveness (GETE), asthma symptoms, corticosteroid use, exacerbation rate, asthma control, quality of life, healthcare utilisation and safety during a 24-month observation period.ResultsOne hundred and fourteen patients from the Czech Republic were enrolled in the eXpeRience registry. A total of 88.9% of the patients were evaluated as responders to omalizumab according to the GETE assessment at week 16. From baseline to month 24: mean change in forced expiratory volume in 1 s (FEV1) was 137 ml and the daily dose of OCS decreased (11.6 mg to 6.4 mg prednisolone equivalent); the percentage of patients with no severe clinically significant exacerbations increased (29.5% to 95.1%); Asthma Control Test scores improved (12.4 to 17.3) and mean total number of days of asthma-related medical healthcare use decreased (6.8 days to 0.4 days).ConclusionsThe results of this subgroup analysis support the evidence that add-on omalizumab therapy is effective and well tolerated for management of patients with uncontrolled persistent AA in the Czech Republic. Global evaluation of treatment effectiveness assessment is a reliable predictor of long-term response to omalizumab treatment.

Cost Effectiveness of Pharmacological Treatments for Asthma: A Systematic Review.

The objective of this article was to summarize the findings of all the available studies on alternative pharmacological treatments for asthma and assess their methodological quality, as well as to identify the main drivers of the cost effectiveness of pharmacological treatments for the disease. A systematic review of the literature in seven electronic databases was conducted in order to identify all the available health economic evidence on alternative pharmacological treatments for asthma published up to April 2017. The reporting quality of the included studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. A total of 72 studies were included in the review, classified as follows: medications for acute asthma treatment (n = 5, 6.9%); inhaled corticosteroids (ICS) administered alone or in conjunction with long-acting β-agonists (LABA) or tiotropium for chronic asthma treatment (n = 38, 52.8%); direct comparisons between different combinations of ICS, ICS/LABA, leukotriene receptor antagonists (LTRA), and sodium cromoglycate for chronic asthma treatment (n = 14, 19.4%); and omalizumab for chronic asthma treatment (n = 15, 20.8%). ICS were reported to be cost effective when compared with LTRA for the management of persistent asthma. In patients with inadequately controlled asthma taking ICS, the addition of long-acting β-agonist (LABA) preparations has been demonstrated to be cost effective, especially when combinations of ICS/LABA containing formoterol are used for both maintenance and reliever therapy. In patients with uncontrolled severe persistent allergic asthma, omalizumab therapy could be cost effective in a carefully selected subgroup of patients with the more severe forms of the disease. The quality of reporting in the studies, according to the CHEERS checklist, was very uneven. The main cost-effectiveness drivers identified were the cost or rate of asthma exacerbations, the cost or rate of the use of asthma medications, the asthma mortality risk, and the rate of utilization of health services for asthma. The present findings are in line with the pharmacological recommendations for stepwise management of asthma given in the most recent evidence-based clinical practice guidelines for the disease. The identified reporting quality of the available health economic evidence is useful for identifying aspects where there is room for improvement in future asthma cost-effectiveness studies.

In search of clinically relevant parameters to monitor successful omalizumab therapy in allergic asthma.

Background: Omalizumab is approved as add-on therapy for the treatment of severe uncontrolled allergic asthma. Increase in quality of life and decrease of exacerbations and hospital admission, as well as immunmodulatory effects have been described with omalizumab therapy. However, to date there are few parameters to monitor success and to evaluate the individual advantage of this therapy for the patient. Furthermore, no reliable parameter to predict response to treatment exists so far. The aim of this study was to define an easily applicable parameter for response to treatment with omalizumab. Method: 43 patients with allergic asthma were treated with omalizumab at a dose of at least 0,016 mg/kg/IgE every 4 weeks. Before, and 12 weeks after initiation of therapy, bodyplethysmography including airway resistance was performed. Efficacy of treatment was judged by the attending physician on the basis of a five point chart. Furthermore, a differential blood count was performed before, and 12 weeks after initiation of treatment. Total and specific IgE against all relevant antigens were determined before start of therapy. Results: Airway resistance in patients with response to treatment with omalizumab (responders) was significantly decreased in comparison to patients without clinical benefit (non-responder). The number of eosinophil granulocytes in the peripheral blood was decreased in both groups without significant difference. Response to therapy was associated with younger age and lower levels of specific IgE against the allergen with the highest sIgE-level (seasonal and perennial), but not with the sIgE level of the perennial allergens in general. Conclusion: Measurement of airway resistance might be an additional parameter for monitoring response to therapy with omalizumab. High specific IgE levels, for both perennial and concomitant seasonal allergens as well as increasing age, seem to predict less favorable treatment outcomes.

Innovative treatments for severe refractory asthma: how to choose the right option for the right patient?

The increasing understanding of the molecular biology and the etiopathogenetic mechanisms of asthma helps in identification of numerous phenotypes and endotypes, particularly for severe refractory asthma. For a decade, the only available biologic therapy that met the unmet needs of a specific group of patients with severe uncontrolled allergic asthma has been omalizumab. Recently, new biologic therapies with different mechanisms of action and targets have been approved for marketing, such as mepolizumab. Other promising drugs will be available in the coming years, such as reslizumab, benralizumab, dupilumab and lebrikizumab. Moreover, since 2010, bronchial thermoplasty has been successfully introduced for a limited number of patients. This is a nonpharmacologic endoscopic procedure which is considered a promising therapy, even though several aspects still need to be clarified. Despite the increasing availability of new therapies, one of the major problems of each treatment is still the identification of the most suitable patients. This sudden abundance of therapeutic options, sometimes partially overlapping with each other, increases the importance to identify new biomarkers useful to guide the clinician in selecting the most appropriate patients and treatments, without forgetting the drug-economic aspects seen in elevated direct cost of new therapies. The aim of this review is, therefore, to update the clinician on the state of the art of therapies available for refractory asthma and, above all, to give useful directions that will help understand the different choices that sometimes partially overlap and to dispel the possible doubts that still exist.

Cost-effectiveness of omalizumab add-on to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting

Objective: Omalizumab add-on to standard-of-care therapy has proven to be efficacious in severe asthma patients for whom exacerbations cannot be controlled otherwise. Moreover, evidence from different healthcare settings suggests reduced healthcare resource utilization with omalizumab. Based on these findings, this study aimed to assess the cost-effectiveness of the addition of omalizumab to standard-of-care therapy in patients with uncontrolled severe allergic asthma in a Brazilian healthcare setting.Methods: A previously published Markov model was adapted using Brazil-specific unit costs to compare the costs and outcomes of the addition of omalizumab to standard-of-care therapy vs standard-of-care therapy alone. Model inputs were largely based on the eXpeRience study. Costs and health outcomes were calculated for lifetime-years and were annually discounted at 5%. Both one-way and probabilistic sensitivity analyses were performed.Results: An additional cost of R$280,400 for 5.20 additional quality-adjusted life-years was estimated with the addition of omalizumab to standard-of-care therapy, resulting in an incremental cost-effectiveness ratio of R$53,890. One-way sensitivity analysis indicated that discount rates, standard-of-care therapy exacerbation rates, and exacerbation-related mortality rates had the largest impact on incremental cost-effectiveness ratios.Limitations: Assumptions of lifetime treatment adherence and rate of future exacerbations, independent of previous events, might affect the findings. The lack of Brazilian patients in the eXpeRience study may affect the findings, although sample size and baseline characteristics suggest that the modeled population closely resembles Brazilian severe allergic asthma patients.Conclusion: Results indicate that omalizumab as an add-on therapy is more cost-effective than standard-of-care therapy alone for Brazilian patients with uncontrolled severe allergic asthma, based on the World Health Organization’s cost-effectiveness threshold of up to 3-times the gross domestic product.