Treatment of severe persistent asthma with IL-6 receptor blockade (original) (raw)

Immunomodulatory and biologic therapies for severe refractory asthma

Respiratory Medicine, 2008

Despite undoubted efficacy of the combination of inhaled corticosteroids and b 2 -agonists for most asthmatic patients with moderate-to-severe disease, there remains w10% of the asthmatic population with serious unremitting symptoms, resulting in considerable impact on quality of life, disproportionate use of health care resources, and adverse effects from regular systemic steroid use. In an ideal world, optimal treatment of severe refractory asthma should achieve the best possible asthma control and quality of life with the least dose of systemic corticosteroids. The choice and formulation of therapeutic agent are dictated by the severity of disease and may include immunological modifiers and biologic therapies. Unfortunately, current asthma guidelines offer little contribution to the management of the challenging patient with severe refractory asthma and none of them have addressed therapeutic alternatives to oral corticosteroids. This article reviews the current evidence for immunomodulating and biologic approaches in severe refractory asthma. ª

Clinical impact of omalizumab treatment in children with severe asthma. Report of a local experience

Archivos Argentinos de Pediatria, 2019

Omalizumab, an anti-IgE monoclonal antibody, is indicated for the treatment of severe asthma. A longitudinal (pre-/post-intervention), observational, analytical study was conducted to assess the clinical and functional course of patients with uncontrolled severe asthma, 16 weeks before and after treatment. Asthma was controlled in 17 cases (p = 0.00001). Exacerbations were reduced by 48.5 % (p = 0.009) and severe crises, by 100 % (p = 0.001). Before omalizumab treatment, 16 patients (94 %) had exacerbations, whereas 10 (59 %) had them after treatment (p = 0.005). None of the patients was hospitalized (p = 0.007). The dose of inhaled corticosteroids was reduced by 20 % (0.002); the number of patients using continuous oral corticosteroids (p = 0.01), salbutamol (p = 0.001), and oral corticosteroids (p = 0.003) also decreased. Pulmonary function was not affected. Two patients had mild adverse reactions. Omalizumab achieved an adequate asthma control in patients with severe asthma.

Therapeutic interventions in severe asthma

The World Allergy Organization journal, 2016

The present paper addresses severe asthma which is limited to 5-10% of the overall population of asthmatics. However, it accounts for 50% or more of socials costs of the disease, as it is responsible for hospitalizations and Emergency Department accesses as well as expensive treatments. The recent identification of different endotypes of asthma, based on the inflammatory pattern, has led to the development of tailored treatments that target different inflammatory mediators. These are major achievements in the perspective of Precision Medicine: a leading approach to the modern treatment strategy. Omalizumab, an anti-IgE antibody, has been the only biologic treatment available on the market for severe asthma during the last decade. It prevents the linkage of the IgE and the receptors, thereby inhibiting mast cell degranulation. In clinical practice omalizumab significantly reduced the asthma exacerbations as well as the concomitant use of oral glucocorticoids. In the "Th2-high as...

Severe Asthma and Biological Therapy: When, Which, and for Whom

Pulmonary therapy, 2019

Asthma is a heterogeneous chronic inflammatory disease of the airways that affects approximately 300 million people worldwide. About 5-10% of all asthmatics suffer from severe or uncontrolled asthma, associated with increased mortality and hospitalization, reduced quality of life, and increased health care costs. In recent years, new treatments have become available, and different asthma phenotypes characterized by specific biomarkers have been identified. Biological drugs are currently indicated for patients with severe asthma that is not controlled with recommended treatments. They are mostly directed against inflammatory molecules of the type 2 inflammatory pathway and are effective at reducing exacerbations, maintaining control over asthma symptoms, and reducing systemic steroid use, which is associated with well-known adverse events. Although biological drugs for severe asthma have had a major impact on the management of the disease, there is still a need for head-to-head comparison studies of biologics and to identify new biomarkers for asthma diagnosis, prognosis, and response to treatment. Identifying novel biomarkers could facilitate the development of therapeutic strategies that are precisely tailored to each patient's requirements.

Efficacy and effectiveness of omalizumab in the treatment of childhood asthma

Expert review of respiratory medicine, 2018

Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E, a mediator involved in the clinical manifestations of allergic asthma. Evidence for its efficacy and safety in the treatment of moderate-to-severe allergic asthma is based primarily on studies in adolescents and adults. However, there is increasing evidence of its utility in children with allergic asthma aged 6-12 years. Areas covered: This article reviews efficacy, safety, and effectiveness of omalizumab in the treatment of moderate-to-severe allergic asthma in children aged 6-12 years in clinical trials and in studies in clinical practice. Pharmacoeconomic aspects of its use among this population and the positioning of omalizumab in pediatric asthma management guidelines are also discussed. Additionally, an algorithm for the management of poorly controlled severe pediatric asthma in children older than 6 years is proposed. Electronic databases, such as PubMed, were searched for terms Asthma an...

Tailored therapy for severe asthma

Multidisciplinary respiratory medicine, 2015

Patients with severe asthma or COPD have often a suboptimal symptom control due to inadequate treatment. A better understanding of pathogenetic mechanisms, phenotypes, endotypes and the new technologies available in the fields of molecular biology and immunogenetics have made it possible to synthesize specific monoclonal antibodies virtually able to interact with any target antigen, or to open a way for new therapeutic target options. At the moment, the only biologic drug available in clinical practice is omalizumab. To overcome the limits of omalizumab, the research has focused on new monoclonal antibodies presenting higher avidity for IgE (e.g. ligelizumab and lumiximab) and ability to interact also with low affinity IgE receptor (FcϵRII). At present, many new biological drugs with different mechanisms of action and targets are matter of research. It is very important to identify the asthmatic phenotype in order to select the most appropriate drug for the individual patient. The m...

Daclizumab Improves Asthma Control in Patients with Moderate to Severe Persistent Asthma

American Journal of Respiratory and Critical Care Medicine, 2008

Rationale: Airway inflammation in asthma is associated with increased activated CD25 1 T cells, IL-2, and soluble IL-2 receptors (IL-2Rs). Objectives: A randomized, double-blinded, placebo-controlled study was used to evaluate the safety and efficacy of daclizumab, a humanized IgG1 monoclonal antibody against the IL-2R a chain (CD25) of activated lymphocytes, in adults with moderate to severe persistent asthma. Methods: Patients with obstructive pulmonary functions, despite inhaled corticosteroids (ICS), were switched to equivalent dose inhaled triamcinolone acetate acetonide (TAA). Patients dependent on ICS were randomized (3:1) to daclizumab (intravenous loading dose, 2 mg/kg, then 1 mg/kg) or placebo every 2 weeks, added to stable-dose TAA through Week 12 (Treatment Period 1). Over Weeks 12-20 (Treatment Period 2), patients tapered TAA while on the study drug, and were followed for 16 weeks off the study drug. Measurements and Main Results: Among 115 evaluable patients (88 daclizumab, 27 placebo), groups had similar age, disease duration, and length of ICS use. During Treatment Period 1, daclizumab improved FEV 1 (daclizumab, 4.4 6 1.80% vs. placebo, 1.5 6 2.39%; P 5 0.05), and reduced daytime asthma symptoms (P 5 0.018) and short-acting inhaled b 2-agonist use (P 5 0.009). Daclizumab treatment prolonged time to exacerbation (P 5 0.024). Adverse events were evenly distributed between groups, although there were more serious adverse events in the patients treated with daclizumab. Conclusions: Daclizumab improved pulmonary function and asthma control in patients with moderate to severe chronic asthma inadequately controlled on ICS. The mechanism of action likely involves inhibition of proinflammatory cytokine generation by IL-2R blockade in activated T cells. Clinical trial registered with www.clinicaltrials.gov (NCT00028288).

Update on optimal use of omalizumab in management of asthma

Journal of Asthma and Allergy, 2011

Omalizumab is a humanized monoclonal anti-IgE antibody recently approved for the treatment of severe allergic asthma. This drug inhibits allergic responses by binding to serum IgE, thus preventing interaction with cellular IgE receptors. Omalizumab is also capable of downregulating the expression of high affinity IgE receptors on inflammatory cells, as well as the numbers of eosinophils in both blood and induced sputum. The clinical effects of omalizumab include improvements in respiratory symptoms and quality of life, paralleled by a reduction of asthma exacerbations, emergency room visits, and use of systemic corticosteroids and rescue bronchodilators. Omalizumab is relatively well-tolerated, and only rarely induces anaphylactic reactions. Therefore, this drug represents a valid option as add-on therapy for patients with severe persistent allergic asthma inadequately controlled by high doses of standard inhaled treatments.