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Asma eosinofílica greu; Comparació indirecta del tractament; Mepolizumab Severe eosinophilic asthma; Indirect treatment comparison; Mepolizumab Asma eosinofílica severa; Comparación de tratamiento indirecto; Mepolizumab Aim To analyse the cost-effectiveness of MEP with standard of care (SoC) versus other anti-IL-5 therapies approved for the treatment of severe eosinophilic asthma (SEA) patients, within the Spanish National Health System (NHS) perspective. Methods A Markov model with a 4-week cycle length was used to compare MEP with BEN and RES as therapies added to SoC in the management of SEA, in terms of cost per QALY gained and incremental cost-effectiveness ratio (ICER). Costs (€2019) were obtained from public sources, while utilities and transition probabilities were retrieved from literature, e.g. network meta-analysis. Continuation criteria for biological treatment and reduction of oral corticosteroids (OCS) was set at 50% minimum reduction of exacerbation rate. Adverse events related to chronic OCS use included diabetes, osteoporosis, cataracts, acute myocardial infarct, and peptic ulcer. The analysis was performed over a 5-year time horizon from the National Healthcare System (NHCS) perspective, with a yearly discount rate of 3% applied to both costs and QALYs. Probabilistic sensitivity analysis and univariate deterministic sensitivity analysis were performed to address uncertainty around the cost-effectiveness results. Results On top of SoC, the model indicates that MEP is dominant (lower cost, higher benefit) compared to BEN and RES: For BEN and RES, respectively, treatment with MEP had a point estimate of 0.076 and 0.075 additional QALYs, and savings of €3,173.47 and €7,772.95 per patient. The findings were robust to variation as estimated using sensitivity analysis. Conclusions MEP is a cost-effective treatment in comparison with BEN and RES added to SoC for patients with SEA in the Spanish setting. This study was funded by GlaxoSmithKline [Study code: HO-19-19968].

Anti-interleukin 5 (IL-5) and anti-IL-5 receptor α monoclonal antibodies markedly decrease airway and peripheral blood eosinophil numbers and are thus highly effective in reducing asthma exacerbations. Nonetheless, these biologics do not completely resolve exacerbations. There is very little information on the cellular nature of exacerbations during treatment with biologics. Using illustrative clinical case scenarios, we highlight the importance of carefully characterizing asthmatics at the time of exacerbation and recognizing neutrophilic causes of exacerbations to ensure optimal management. While an eosinophilic exacerbation may improve with more corticosteroids or by switching to another anti-IL-5 monoclonal antibody, a noneosinophilic exacerbation will likely not. An infective exacerbation needs to be recognized, and the pathogen must be identified and treated with the appropriate antimicrobial agent.

Background Allergic Fungal Rhinosinusitis (AFRS) is a non-invasive fungal disease that results from chronic allergic inflammation of the sinonasal mucosa. Failure to respond to mainstay medical therapies and sinus surgery leaves AFRS patients with limited alternatives and a decreased quality of life. Mepolizumab is a known IL-5 antagonist for patients with severe eosinophilic asthma. Objective To identify the efficacy of mepolizumab on improving Modified Lund-Kennedy (MLK) endoscopic scores in recalcitrant AFRS patients with asthma. Methods Retrospective chart review of 27 recalcitrant AFRS patients with asthma receiving a monthly mepolizumab injection between January 2017 and July 2019. Patients were evaluated endoscopically at baseline and at each follow-up visit every 6–8 weeks until their third visit. Secondary outcomes included SNOT-22 scores, serum eosinophil counts and the rate of prednisone rescues required in patients receiving mepolizumab compared to a retrospective control arm. Results Total median MLK scores improved significantly for all patients over three follow-up visits (6[4,7], 4[2,6], 5[2,6], 3.5[2.25,5]; p = 0.04). Amongst patients with a baseline polyposis score of 1 or more, combined MLK edema and polyposis sub-scores significantly improved (6[5.25,6], 3.5[2.25,5,75], 4[2.75,5.25], 4[3,4]; p = 0.02) versus patients with no polyposis (4[3,4], 3[1,4], 4[2,4], 3[0,4]; p = 0.90). Total SNOT-22 scores (56 vs 43; p = 0.04) and eosinophil counts (0.40 × 109/L vs 0.00 × 109/L; p Conclusion Mepolizumab injections administered once monthly as an adjunctive treatment for recalcitrant AFRS patients with asthma appear to significantly reduce endoscopic signs of inflammation, patient-reported symptomatology and serum eosinophil levels. Patients with evidence of more severe endoscopic inflammation appear to benefit the most. Adjunctive treatment with mepolizumab does not reduce the need for prednisone rescues.

Asthma exhibits marked heterogeneity in symptoms with severe or refractory asthma representing a clear area of unmet medical need. These patients require more specifically targeted treatments with monoclonal antibody-based biologics targeted at inhibition of the type 2 cytokines IL-4, IL-5 and IL-13 having considerable potential as effective treatments for severe asthma. For the most part, anti-cytokine-based biologic therapies are more likely to give significant clinical benefit in carefully selected patient populations that take asthma phenotypes and endotypes into account.This review is based on recent English-language original articles in Pub Med or MedLine that reported significant clinical findings on the current status, therapeutic potential and safety of the anti-IL-5 biologics mepolizumab, reslizumab and benralizumab in the treatment of severe refractory asthma.Anti-IL-5 treatment appears effective in patients with eosinophilic asthma through exacerbation prevention with accumulating evidence of glucocorticoid-sparing effects with an acceptable safety profile for these biologics.

The interleukin 5 (IL-5) pathway is an important component in the pathophysiology of severe eosinophilic asthma. Mepolizumab is a monoclonal antibody that targets the IL-5 pathway. Clinical trials showed efficacy of Mepolizumab in patients with severe eosinophilic asthma. However, reports on experience with treatment in a real-world cohort are limited.Evaluation of the efficacy and safety of Mepolizumab for treatment of severe eosinophilic asthma in a real-world cohort of patients.A clinical prospective observational trial included all patients18 years treated with Mepolizumab between March 2016 to March 2019 at Rabin Medical Center. The composite primary outcome measures evaluated: increase in FEV1 by≥ 200 ml and/or decrease in exacerbation rate of ≥50% and/or cessation of oral corticosteroids (OCS) treatment or ≥50% decrease in dosage. Also evaluated: blood eosinophil count, adverse events and quality of life.Of 61 patients, 50 (82.0%) achieved the primary outcome. The number of patients who suffered from frequent exacerbations decreased from 52 (85.2%) to 8 (13.1%) (Treatment with mepolizumab was well tolerated and significantly lowered the exacerbation rate and OCS dependence in a real-world cohort of severe eosinophilic asthma patients. Response to therapy was within six months and treatment effect was sustained over time.

In a real-world setting, the clinical response to the anti-IL-5/5R mAbs mepolizumab and benralizumab in patients with severe eosinophilic asthma is independent of co-eligibility with the anti-IgE mAb omalizumabhttps://bit.ly/2NfAitP

Immunoglobulin (Ig) E-mediated food allergy and eosinophilic esophagitis (EoE) are chronic, allergen-mediated disorders characterized by an aberrant TH2 immune response. The development and investigation of biologics for the treatment of IgE-mediated food allergy and eosinophilic esophagitis have provided further insight into the pathophysiology and management of these disorders. This article provides an overview of biologic therapies that are being investigated or have potential as treatments for IgE-mediated food allergy and eosinophilic esophagitis. Identification of EoE phenotypes that are responsive to biologics and investigation of biologics combined with other therapies may help elucidate a role for biologics in EoE.

Several biologics are currently FDA approved for asthma that target Th2 high patients. Unfortunately, 50% of patients with severe asthma do not fit this phenotype of disease and have fewer effective therapeutic options. In the clinical setting, total IgE, FeNO and peripheral blood eosinophils are important tools in defining Th2 high patients with asthma. However, precise biomarkers to predict better response to one specific Th2 high asthma therapy versus another is lacking. It is important to recognize that none of the current medications targeting the Th2 pathway induces persistent immunomodulation or remission.

Mepolizumab (Bosatria(®), GlaxoSmithKline) is a biologic agent developed to treat asthma. It represents a humanized monoclonal antibody of IgG1 κ type, which targets human IL-5 and thus prevents its interaction with the α-chain of the IL-5 receptor. To date, it has not been approved for use in any eosinophil-related disorder; however, several studies have suggested some therapeutic benefit across a spectrum of eosinophil-related disorders. This article evaluates the currently available preclinical and clinical studies, and the impact of mepolizumab against a variety of eosinophilic disorders.

Background The recent development of eosinophil-targeting agents has raised enthusiasm for management of patients with hypereosinophilic syndromes. Roughly half of anti-IL-5-treated patients with corticosteroid-responsive lymphocytic (L-HES) and idiopathic disease variants can be tapered off corticosteroids. Potential consequences of corticosteroid-withdrawal on clonal expansion of pre-malignant CD3-CD4+ T-cells associated with L-HES are a subject of concern. Indeed, corticosteroid treatment inhibits T-cell activation and may lower blood CD3-CD4+ cell counts. On the other hand, previous studies have shown that eosinophils support CD4 T-cell activation, suggesting that targeted eosinophil depletion may negatively regulate these cells. Objectives Effects of eosinophils on CD4 T-cell activation in vitro were investigated as an indirect means of exploring whether treatment-induced eosinophil depletion may affect pathogenic T-cells driving L-HES. Methods Helper (CD4) T-cells and CD3-CD4+ cells from healthy controls and L-HES patients, respectively, were cultured in vitro in presence of anti-CD3/CD28 or dendritic cells. Effects of eosinophils on T-cell proliferation and cytokine production were investigated. Results Eosinophils enhanced CD3-driven proliferation of CD4 T-cells from healthy subjects in vitro, while inhibiting TCR-independent proliferation and IL-5 production by CD3-CD4+ T-cells. Conclusions While this study confirms previous work showing that eosinophils support activation of normal helper T-cells, our in vitro findings with CD3-CD4+ T-cells suggest that eosinophil-depletion may favor activation and expansion of this pathogenic lymphocyte subset. With the ongoing development of eosinophil-targeted therapy for various eosinophilic conditions, the indirect consequences of treatment on the underlying immune mechanisms of disease should be investigated in detail in the setting of translational research programs.