Profile of anti-IL-5 mAb mepolizumab in the treatment of severe refractory asthma and hypereosinophilic diseases

Abstract

Asthma is a complex disorder frequently associated with a poor symptom control, concomitant morbidity, mortality, and significant health care costs due to lack of compliance or inadequate therapeutic options. Interleukin-5 (IL-5) plays a key role in the pathogenesis of eosinophilic disorders, and in the latest years has become a definite target for treatment. Besides asthma, other hypereosinophilic disorders include the hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, sinonasal polyposis, COPD with eosinophilic airway inflammation, allergic rhinitis, atopic dermatitis, eosinophilic esophagitis. The introduction of mepolizumab, a fully humanized monoclonal antibody that binds to IL-5, may represent a useful therapeutic option to control exacerbations and improve asthma-related quality of life in a subgroup of patients with persistent airway eosinophilia and moderate to severe asthma. Several studies carried out in recent years allow, at present, a careful patient selection for appropriate individualized treatment in severe asthma. Further research is anyway needed in order to better understand the pathogenetic mechanisms of asthma and to find new biomarkers. The high costs of biological agents as compared with standard drugs may be largely offset by increased clinical efficacy and good safety profile in selected patients.

Therapeutic Antibody‐Based Drugs in the Treatment of Human Inflammatory Disorders

“…Asthma is a chronic disease of airways where pre-exposure and complement result in cytokine-and allergen-triggered inflammation that is characterised by the dysregulation of IL-4, IL-5 and/or IL-13. Mepolizumab (Nucala) and reslizumab (Cinquair) are IL-5-specificneutralising mAbs that have recently been demonstrated to be capable of preventing and controlling moderate to severe asthma [177,178]. Since eosinophilia is a feature of this condition, mepolizumab is also indicated for other hyper-eosinophilic conditions, such as eosinophilic airway inflammation, allergic rhinitis, atopic dermatitis, and eosinophilic oesophagitis [179].…”

The Pharmacokinetics and Relative Bioavailability of Mepolizumab 100 mg Liquid Formulation Administered Subcutaneously to Healthy Participants: A Randomized Trial

“…Mepolizumab is a humanized, immunoglobulin G1 (IgG1), anti‐interleukin (IL)‐5 monoclonal antibody, which prevents IL‐5 from binding to the IL‐5 receptor complex expressed on eosinophils . This results in the suppression of downstream IL‐5–mediated responses such as T‐helper cell type 2 immune responses .…”

“…Mepolizumab is approved for use in severe eosinophilic asthma and EGPA, and is also currently being explored for the treatment of patients with eosinophilic chronic obstructive pulmonary disease, nasal polyposis, and hypereosinophilic syndrome …”

“…Mepolizumab is a humanized, immunoglobulin G1 (IgG1), anti-interleukin (IL)-5 monoclonal antibody, which prevents IL-5 from binding to the IL-5 receptor complex expressed on eosinophils. 1,2 This results in the suppression of downstream IL-5-mediated responses such as T-helper cell type 2 immune responses. 3,4 In patients with severe eosinophilic asthma, mepolizumab treatment has been shown to reduce exacerbation frequency, decrease oral corticosteroid dependence, and improve health-related quality of life and lung function, compared with placebo.…”

Treating IgE‐mediated diseases via targeting IgE‐expressing B cells using an anti‐CεmX antibody

“…The approval of the anti‐IgE antibody, omalizumab, for the treatment of severe, persistent allergic asthma has stimulated many programs to develop therapeutics targeting cytokines of the type 2 helper T‐cell pathway, such as IL‐4, IL‐13, and IL‐5, and their receptors, and several candidates are currently at the late stages of clinical development . Omalizumab was also approved for chronic idiopathic urticaria in 2014 and mepolizumab, an anti‐IL5 antibody, was approved for eosinophilic asthma in 2015 . This report focuses on the prospective uses of anti‐CεmX, which targets IgE‐expressing B lymphocytes, and how it may provide clinical utility not achievable with omalizumab and other antibodies.…”