Management Of Severe Allergic Asthma Research Articles

Necesidades no cubiertas en asma alérgica grave

Severe asthma affects 3%-10% of the world's population, according to estimates by the Global Initiative for ASTHMA (GINA). Allergic asthma is one of the most common phenotypes of severe asthma and it is characterized by allergen-induced type2 inflammation in which immunoglobulinE (IgE) is a key mediator, making it an important therapeutic target. The introduction of targeted biological therapies or treatments has entered the management for severe asthma in the era of precision medicine, and the goal of treatment is clinical remission of the disease. There is a significant percentage of patients with severe allergic asthma who do not respond to treatments and whose symptoms are not controlled. In this paper, a group of experts in the management of severe allergic asthma reviewed and evaluated the most relevant evidence regarding the pathophysiology and phenotypes of severe allergic asthma, the role of IgE in allergic inflammation, allergen identification, techniques, biomarkers and diagnostic challenges, available treatments and strategies for disease management, with a special focus on biological treatments. From this review, recommendations were developed and validated through a Delphi consensus process with the aim of offering improvements in the management of severe allergic asthma to the professionals involved and identifying the unmet needs in the management of this pathology.

Relevance of TH2 Markers in the Assessment and Therapeutic Management of Severe Allergic Asthma: A Real-Life Perspective.

Although blood eosinophils are currently recognized as the main clinical marker of TH2-type inflammation, their relevance in identifying asthma severity remains a matter of debate. Our retrospective real-life study on severe asthmatics included in the NEONet Italian database aimed to investigate the relevance of blood eosinophil count and fractional exhaled nitric oxide (FeNO) in the clinical assessment of severe asthma and their role as potential predictors of responsiveness to anti-IgE therapy. The cut-off values chosen were 300 eosinophils/mm3 and FeNO of 30 ppm. We evaluated 132 adult patients. No significant differences were observed between the groups (high and low baseline eosinophil counts) in terms of demographic data, total IgE, lung function, patient-reported outcomes, or nasal comorbidities. The Asthma Control Test score and Asthma Quality of Life Questionnaire scores were poorer in patients with FeNO ≥30 ppb than in patients with FeNO <30 ppb. In the high FeNO subgroup, more frequent hospital admissions and a higher number of working days lost in the previous year were registered. A combined score including both eosinophils and FeNO did not improve the accuracy of the individual parameters. In the high-eosinophil subgroup, the proportion of responders to omalizumab was greater and increased at each follow-up time point. Our findings show that blood eosinophil count is not an unequivocal marker of asthma severity, whereas a higher FeNO level is associated with more frequent hospital admissions and more working days lost. Blood eosinophils seem to act as a predictor of response to omalizumab.

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.

Asthma and the Biologics Revolution, Part 2: Failures and the Future Potential

To highlight the evidence behind the various biologics that are being developed for asthma along with their specific targets in the inflammatory cascade and the potential role they serve in the management of allergic asthma. The mainstay of asthma management for the majority of asthmatics is inhaled corticosteroids with or without long-acting beta-agonists and/or leukotriene modifiers and/or tiotropium. However, in the small group of individuals with severe asthma uncontrolled with conventional therapy, biologics have emerged as an effective therapeutic option. Asthma is a chronic heterogenous disease affecting both children and adults. In its severe form, asthma is associated with significant morbidity and mortality along with increased healthcare utilization and costs. Several biologics targeting different areas of the asthmatic inflammatory cascade such as IgE and IL-5 have been approved for the management of severe allergic asthma. Recent advances have helped to further uncover the pathophysiology of asthma which have identified other potential targets for therapy in the moderate-to-severe difficult to treat asthmatic population.

Asthma and the Biologics Revolution, Part 1: Here and Now

To highlight the evidence behind the various approved biologics indicated for asthma along with their specific targets in the inflammatory cascade and the role they serve in the management of allergic asthma. The mainstay of asthma management for the majority of asthmatics is inhaled corticosteroids with or without long-acting beta-agonists and/or leukotriene modifiers and/or tiotropium. However, in the small group of individuals with severe asthma uncontrolled with conventional therapy, biologics have emerged as an effective therapeutic option. Asthma is a chronic heterogenous disease affecting both children and adults. In its severe form, asthma is associated with significant morbidity and mortality along with increased healthcare utilization and costs. Several biologics targeting different areas of the asthmatic inflammatory cascade have been approved and continue to be assessed for the management of severe allergic asthma. Uncovering the pathophysiology of asthma not only has identified potential targets for therapy but also has brought to light the importance of uncovering specific biomarkers that will help aid therapeutic decision-making.

Omalizumab et immunothérapie allergénique : cas clinique et revue de la littérature

Several authors have proposed combined omalizumab and allergen immunotherapy (AIT) in patients suffering from severe allergic asthma to both increase disease control and decrease the severity through targeting the main allergen responsible for the respiratory symptoms. In a female pediatric patient suffering from severe asthma, followed-up at the University Hospital of Montpellier (France), we prescribed an AIT to Alternaria after obtaining symptom control with omalizumab. The patient showed an overall improvement in symptoms after AIT was administered and the disease remained controlled long after cessation of omalizumab. There are only a few publications evaluating the efficacy of the association of these two biotherapies in the management of severe allergic asthma. In addition there is, as yet, no common protocol for the administration of the two prescriptions. This approach to treatment would benefit from standardization in order to optimize the management of severe allergic asthma.

An Update on Anti-IgE Therapy in Pediatric Respiratory Diseases.

Anti-IgE treatment represents a major breakthrough in the therapeutic management of severe allergic asthma. Omalizumab is the unique biologic treatment registered for asthma therapy in children. The clinical efficacy and safety of omalizumab treatment in the pediatric population has been extensively documented in specific trials and consistently expanded from real-life studies. In addition, new experimental evidence suggests that omalizumab may also interfere with the cellular and molecular mechanisms underlying airway remodeling. Novel investigational anti-IgE monoclonal antibodies with improved pharmacodynamic properties are in the pipeline, potentially offering alternative mechanisms of modulating IgE pathway.The aim of this review is to update current knowledge on anti-IgE therapy in pediatric respiratory diseases.

Omalizumab in Children with Severe Allergic Asthma: The Italian Real-Life Experience.

Background: Anti-IgE treatment represents a major breakthrough in the therapeutic management of severe allergic asthma. To date, omalizumab is the only biological drug currently licensed as add-on therapy in children aged > 6 years with moderate-to-severe and severe allergic asthma uncontrolled after treatment with high dose of inhaled corticosteroids plus long-acting inhaled beta2-agonist. The clinical efficacy and safety of omalizumab treatment in the pediatric population has been extensively documented in specific trials and consistently expanded from real-life studies. Our aim is to describe the impact of omalizumab on asthma management, by reporting the results of the first Italian multicenter observational study conducted in children and adolescents with severe allergic asthma.Methods: The study was a 1-year real-life multicenter survey conducted in 13 pediatric allergy and pulmonology tertiary centers in Italy. All patients with confirmed severe allergic asthma from whom Omalizumab add-on treatment was initiated between 2007 and 2015 were included in the study.Results: Forty-seven patients with severe allergic asthma were included in the study. A significant reduction in the number of asthma exacerbations was observed during treatment with omalizumab, when compared with the previous year (1.03 vs 7.2 after 6 months (p<0.001) and 0.8 after 12 months (p<0.001), respectively). Hospital admissions were reduced by 96%. At 12 months, forced expiratory volume in 1 s improved and a corticosteroid sparing effect was observed.No serious adverse events were reported during the follow-up period of 12 months.Conclusion: The results of the first Italian multicenter observational study confirmed that omalizumab is an effective and safe add-on therapy in uncontrolled severe allergic asthma in children.

Challenges in the management of severe allergic asthma in the elderly.

Little is known about the features of asthma and allergy in the elderly. A significant number of elderly patients with asthma have uncontrolled and severe asthma. This review aims to provide an analysis of the literature on the assessment and phenotype of severe allergic asthma in the elderly. Gaps and pitfalls in diagnostic and therapeutic approaches, as well as management of severe allergic asthma in the elderly, are also discussed.

Omalizumab for Severe Asthma: Efficacy Beyond the Atopic Patient?

Several years ago, omalizumab became commercially available for the treatment of severe asthma. It remains the only monoclonal antibody to be marketed for this purpose. Since then, many studies have been published endorsing its efficacy and effectiveness. Concomitantly, evidence of an overlap between atopic and non-atopic severe asthma has emerged. However, there also appears to be some disagreement regarding the value of omalizumab in the management of non-atopic disease, as some studies have failed to show any benefit in these patients. The recent literature has also sought to identify appropriate prognostic biomarkers for the use of omalizumab, other than immunoglobulin (IgE) levels. This article briefly summarizes the evolution of asthma treatment, the pathophysiology of the condition, and the method of action of omalizumab. The author describes the controlled and uncontrolled studies (also named "real-life studies") published in adult and pediatric populations in different countries and expresses his view on the current place of the drug in the management of severe allergic asthma. He offers a personal perspective on the recent evidence for the use of omalizumab in non-atopic patients, highlighting the implications for current clinical practice and the gaps in our knowledge. The author justifies his belief that omalizumab is not only an IgE-blocking drug and should be considered as a disease-modifying therapy because of its multiple effects on different biologic pathways. Finally, some areas for future research are indicated.

Outcome Of Childhood Asthma Observational Follow-up Study In First 4 Years In Japan

M O N D A Y 553 Omalizumab Improves Patient-Reported Outcomes In Patients With Allergic (IgE-mediated) Asthma W.H. Yang, P. Georgiou, J. Canvin, C. Chen, G. Peachey; Allergy & Asthma Research Centre, Ottawa, ON, CANADA, Novartis Horsham Research Centre, Horsham, UNITED KINGDOM, Novartis Pharmaceuticals, East Hanover, NJ. RATIONALE: Goals of asthma management are to optimise asthma control and improve health-related quality of life (QoL). Patient-reported outcomes (PROs) such as the asthma control test (ACT), the asthma control questionnaire (ACQ), and the asthma quality of life questionnaire (AQLQ) are important in evaluating the impact of asthma treatment. Omalizumab has demonstrated QoL improvements in clinical trials, but real-world evaluation is desirable. METHODS: eXpeRience is a multicenter, non-interventional, singlearm, observational registry evaluating the efficacy and safety of omalizumab in patients with allergic asthma. Interim data are available forWeek 16 and Month 8 of this 2-year registry. Data are presented for the ACT, ACQ, AQLQ and mini-AQLQ. Values are means6SDs. RESULTS: This analysis included 876 patients (age 44.9615.12 years). The ACToverall score at baselinewas 12.964.49. Omalizumab resulted in clinically meaningful changes from baseline (>_3 point increase) at Week 16 (5.264.70) and Month 8 (6.165.30). Omalizumab recipients also had clinically relevant changes (>_0.5 point decrease) in ACQ overall scores at Week 16 (-0.9860.989) and Month 8 (-0.7461.174) compared with baseline (overall score at baseline 2.760.954). Asthma-related QoL also improved. Overall AQLQ and mini-AQLQ scores at baseline were 4.2261.281 and 3.8161.180, respectively. Clinically meaningful improvements (>_0.5 point increase) in QoL scores were observed following both 16 weeks (AQLQ, 0.8960.932 and; mini-AQLQ 1.1061.139) and 8 months of omalizumab treatment (AQLQ 1.0461.341; mini-AQLQ 1.2461.323). CONCLUSIONS: Treatment with omalizumab was associated with clinically meaningful and sustained improvements in patient reported outcomemeasures of asthma control and asthma-related QoL in real-world management of severe allergic asthma.