A review of treatment with mepolizumab, an anti–IL-5 mAb, in hypereosinophilic syndromes and asthma William W. Busse, MD, Johannes Ring, MD, PhD, Johannes.

Slides:

Advertisements

Similar presentations

Control of immunopathology during chikungunya virus infection Caroline Petitdemange, PhD, Nadia Wauquier, PhD, Vincent Vieillard, PhD Journal of Allergy.

Advertisements

Biologics in Asthma—The Next Step Toward Personalized Treatment

The Inhaled Steroid Treatment As Regular Therapy in Early Asthma (START) study 5- year follow-up: Effectiveness of early intervention with budesonide in.

Adherence with montelukast or fluticasone in a long-term clinical trial: Results from the Mild Asthma Montelukast Versus Inhaled Corticosteroid Trial

Reduced exhaled nitric oxide values in children with asthma after inpatient rehabilitation at high altitude Johannes Huss-Marp, MD, Ursula Krämer, PhD,

Alalia Berry, MD, William W. Busse, MD

Fatty acids, inflammation, and asthma

Endotype-driven care pathways in patients with chronic rhinosinusitis

The role of viruses in acute exacerbations of asthma

Eosinophilic Esophagitis: Is It All Allergies?

Sputum indoleamine-2, 3-dioxygenase activity is increased in asthmatic airways by using inhaled corticosteroids Kittipong Maneechotesuwan, MD, PhD, Sirinya.

Treatment of chronic rhinosinusitis with intranasal amphotericin B: A randomized, placebo-controlled, double-blind pilot trial Jens U. Ponikau, MD, David.

Stephen J. Fowler, MD, Gaël Tavernier, PhD, Robert Niven, MD

Alefacept (lymphocyte function-associated molecule 3/IgG fusion protein) treatment for atopic eczema Dagmar Simon, MD, Jennifer Wittwer, MD, Ganna Kostylina,

Biologics in patients with skin diseases

Jennifer L. Ingram, PhD, Monica Kraft, MD

Der p 1 suppresses indoleamine 2, 3-dioxygenase in dendritic cells from house dust mite–sensitive patients with asthma Kittipong Maneechotesuwan, MD,

Dorothy M. Ryan, MD, Stephen J. Fowler, MD, Robert M. Niven, MD

Is 9 more than 2 also in allergic airway inflammation?

Fatty acids, inflammation, and asthma

Mepolizumab, a humanized anti–IL-5 mAb, as a treatment option for severe nasal polyposis Philippe Gevaert, MD, PhD, Nicholas Van Bruaene, MD, Tom Cattaert,

Biology and Treatment of Eosinophilic Esophagitis

Yuichi Teraki, MD, Aika Sakurai, MD, Seiichi Izaki, MD

Anti–IL-5 treatments in patients with severe asthma by blood eosinophil thresholds: Indirect treatment comparison William Busse, MD, Geoffrey Chupp,

Asthma symptom re-emergence after omalizumab withdrawal correlates well with increasing IgE and decreasing pharmacokinetic concentrations Raymond G.

An Eosinophil Hypothesis for Functional Dyspepsia

Michel Laviolette, MD, David L

Omar Tliba, PhD, DVM, Reynold A. Panettieri, MD

Mepolizumab as a steroid-sparing treatment option in patients with Churg-Strauss syndrome Sophia Kim, MD, Gautham Marigowda, MD, Eyal Oren, MD, Elliot.

A survivor: The eosinophil as a regulator in asthma

High eosinophil count: A potential biomarker for assessing successful omalizumab treatment effects William Busse, MD, Sheldon Spector, MD, Karin Rosén,

Time for a paradigm shift in asthma treatment: From relieving bronchospasm to controlling systemic inflammation Leif Bjermer, MD Journal of Allergy.

Early decreases in blood eosinophil levels with reslizumab

Pathophysiology of the inflammatory response

Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase

The Management of Eosinophilic Esophagitis

Inflammatory cells, cytokine and chemokine expression in asthma immunocytochemistry and in situ hybridization Qutayba Hamid, MD, PhD, Editor Journal.

6. Asthma Journal of Allergy and Clinical Immunology

Budesonide delivered by Turbuhaler is effective in a dose-dependent fashion when used in the treatment of adult patients with chronic asthma William.

What is an “eosinophilic phenotype” of asthma?

H. William Kelly, PharmD Journal of Allergy and Clinical Immunology

Autophagy: Nobel Prize 2016 and allergy and asthma research

Adherence with montelukast or fluticasone in a long-term clinical trial: Results from the Mild Asthma Montelukast Versus Inhaled Corticosteroid Trial

Hypereosinophilic syndrome: A multicenter, retrospective analysis of clinical characteristics and response to therapy Princess U. Ogbogu, MD, Bruce S.

Mepolizumab as a corticosteroid-sparing agent in lymphocytic variant hypereosinophilic syndrome Florence Roufosse, MD, PhD, Aurore de Lavareille, PhD,

Pathogenesis of allergic rhinitis

A randomized, double-blind trial of the effect of treatment with montelukast on bronchial hyperresponsiveness and serum eosinophilic cationic protein.

Asthma control can be maintained when fluticasone propionate/salmeterol in a single inhaler is stepped down Eric D. Bateman, MD, Loretta Jacques, PhD,

Cagri Yildirim-Toruner, MD, Betty Diamond, MD

Therapeutic strategies to reduce asthma exacerbations

Anti–IL-5 (mepolizumab) therapy for eosinophilic esophagitis

Molecular and cellular mechanisms of allergic disease

Xiu-Min Li, MD, LaVerne Brown, PhD

Anti–IL-5 therapy reduces mast cell and IL-9 cell numbers in pediatric patients with eosinophilic esophagitis Iris M. Otani, MD, Arjun A. Anilkumar,

Esophageal eosinophilia caused by milk proteins: From suspicion to evidence based on 2 case reports Soledad Terrados Cepeda, MD, Dario Antolin-Amerigo,

Sustained response to mepolizumab in refractory Churg-Strauss syndrome

An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment Eli O. Meltzer, MD, Robert B. Berkowitz,

Short course of systemic corticosteroids in sinonasal polyposis: A double-blind, randomized, placebo-controlled trial with evaluation of outcome measures

A pilot study of equal doses of 10% IGIV given intravenously or subcutaneously Shilpa H. Desai, BS, MD, Akhil Chouksey, MD, John Poll, RN, Melvin Berger,

Statistical issues in clinical trials that involve the double-blind, placebo-controlled food challenge Vernon M. Chinchilli, PhD, Laura Fisher, MD, Timothy.

Eosinophilic gastrointestinal disorders (EGID)

Systemic responses after bronchial aspirin challenge in sensitive patients with asthma Joanna S. Makowska, MD, PhD, Janina Grzegorczyk, PhD, Barbara Bienkiewicz,

News Beyond Our Pages Journal of Allergy and Clinical Immunology

Statins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase

An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment Eli O. Meltzer, MD, Robert B. Berkowitz,

Natural history of cow’s milk allergy

Sputum indoleamine-2, 3-dioxygenase activity is increased in asthmatic airways by using inhaled corticosteroids Kittipong Maneechotesuwan, MD, PhD, Sirinya.

Primary prevention of asthma and allergy

Mepolizumab efficacy in patients with severe eosinophilic asthma receiving different controller therapies Frank C. Albers, MD, PhD, Robert G. Price,

Advances in mechanisms of allergic disease in 2016

Presentation transcript:

A review of treatment with mepolizumab, an anti–IL-5 mAb, in hypereosinophilic syndromes and asthma William W. Busse, MD, Johannes Ring, MD, PhD, Johannes Huss-Marp, MD, Jean-Emmanuel Kahn, MD Journal of Allergy and Clinical Immunology Volume 125, Issue 4, Pages 803-813 (April 2010) DOI: 10.1016/j.jaci.2009.11.048 Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Schematic diagram of an eosinophil and its multifunctional effects. Eosinophils are bilobed granulocytes with eosinophilic-staining secondary granules, which contain 4 primary cationic proteins, designated eosinophil peroxidase (EPO), major basic protein (MBP), eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN). All 4 proteins are cytotoxic molecules; in addition, ECP and EDN are ribonucleases. Eosinophils respond to diverse stimuli, including nonspecific tissue injury, viral infections, allografts, allergens, and tumors. In addition to releasing their preformed cationic proteins, eosinophils can release a variety of cytokines, chemokines, lipid mediators, and neuromodulators. Eosinophils directly communicate with T cells and mast cells in a bidirectional manner. Eosinophils activate T cells by serving as antigen-presenting cells, and eosinophil-derived MBP is a mast cell secretagogue. Eosinophils can also regulate T-cell polarization through synthesis of indoleamine 2,3-dioxygenase (IDO), an enzyme involved in oxidative metabolism of tryptophan, catalyzing the conversion of tryptophan to kynurenines (KYN), a regulator of TH1/TH2 balance. MIP, Macrophage inflammatory protein; NGF, nerver growth factor; VIP, vasointestinal peptide. From Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol 2006;24:147-74.1 Journal of Allergy and Clinical Immunology 2010 125, 803-813DOI: (10.1016/j.jaci.2009.11.048) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 A and B, Eosinophil blood counts in 2 patients with HESs treated with 3 intravenous doses of mepolizumab 10 mg/kg (750 mg maximum) at intervals of 4 weeks (anti–IL-5 = mepolizumab). From Garrett JK, Jameson SC, Thomson B, Collins MH, Wagoner LE, Freese DK, et al. Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes. J Allergy Clin Immunol 2004;113:115-9.45 Journal of Allergy and Clinical Immunology 2010 125, 803-813DOI: (10.1016/j.jaci.2009.11.048) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Effects of mepolizumab 750 mg on corticosteroid requirements and blood eosinophil counts in patients with HESs in the pivotal double-blind, randomized, placebo-controlled trial. Results are shown for the overall population and according to the daily prednisone dose at baseline (≤30 mg or >30 mg). A, Percentage of patients achieving a prednisone dose of ≤10 mg/d for ≥8 consecutive weeks (primary endpoint). B, Percentage of patients achieving a blood eosinophil count of <600 cells/μL for ≥8 consecutive weeks. Adapted from Rothenberg ME, Klion AD, Roufosse FE, Kahn JE, Weller PF, Simon HU, et al. Treatment of the hypereosinophilic syndrome with mepolizumab. N Engl J Med 2008;358:1215-28.46 Journal of Allergy and Clinical Immunology 2010 125, 803-813DOI: (10.1016/j.jaci.2009.11.048) Copyright © 2010 American Academy of Allergy, Asthma & Immunology Terms and Conditions