Anti-IgE Therapy in Asthma and Allergy PDF
Preview Anti-IgE Therapy in Asthma and Allergy
Anti-IgE Therapy in Asthma and Allergy Anti-IgE Therapy in Asthma and Allergy Syed Hasan Arshad,DM,MRCP Director of the David Hide Asthma and Allergy Centre,Isle of Wight, UK and Director of Clinical Trials,Department of Medical Specialties,Southampton General Hospital,Southampton,UK K Suresh Babu,MD,DNB Clinical Research Fellow,Respiratory,Cell and Molecular Biology Research Division,University of Southampton School of Medicine, Southampton,UK Stephen T Holgate,BSc,MD,DSc,FRCP,FRCPath, FIBiol,CBiol,FmedSci Medical Research Council Professor of Immunopharmacology at the University of Southampton,Southampton General Hospital, Southampton,UK The views expressed in this publication are those of the authors and not necessarily those of Martin Dunitz Ltd. © 2001 Martin Dunitz Ltd,a member of the Taylor & Francis group First published in the United Kingdom in 2001 by Martin Dunitz Ltd The Livery House 7–9 Pratt Street London NW1 0AE Tel: +44 (0) 207 482 2202 Fax: +44 (0) 207 267 0159 E-mail: [email protected] Website: http://www.dunitz.co.uk This edition published in the Taylor & Francis e-Library, 2002. All rights reserved.No part of this publication may be reproduced,stored in a retrieval system,or transmitted,in any form or by any means,electronic, mechanical,photocopying,recording,or otherwise, without the prior permission of the publisher or in accordance with the provisions of the Copyright, Designs and Patents Act 1988 or under the terms of any licence permitting limited copying issued by the Copyright Licensing Agency,90 Tottenham Court Road, London W1P 0LP. A CIP record for this book is available from the British Library. ISBN 1 84184 0904 (Print Edition) Distributed in the USA,Canada and Brazil by: Blackwell Science Inc. Commerce Place,350 Main Street Malden MA 02148,USA Tel:1 800 215 1000 Cover image:Interactions between CD4 T cells and B cells that are important in IgE synthesis.Adapted with permission from Busse WW, Lemanske RF.Advances in immunology:asthma. NJEM2001;344:353.Copyright © 2001 Massachusetts Medical Society.All rights reserved. ISBN 0-203-42170-1 Master e-book ISBN ISBN 0-203-44590-2 (Adobe eReader Format) Contents Preface vii 1. What is asthma and allergy? 1 2. What is immunoglobulin E? 10 3. Synthesis and regulation of IgE 18 4. Allergic inflammation and the role of IgE 24 5. Current management of asthma and allergy 31 6. Anti-IgE as a therapeutic strategy 37 7. Efficacy and safety of anti-IgE in asthma 44 8. Efficacy and safety of anti-IgE in allergic rhinitis 51 9. Future prospects for IgE in the treatment of allergic 56 disorders Further reading 60 Index 63 v Preface The discovery by Prausnitz and Küstner in 1921 of reagin,the circulating substance that could passively transfer the immediate allergic response from one individual to another,stimulated a 50-year search for the molecular basis of this phenomenon.The identification of reagin as IgE independently by Ishizakas and Johansson in the late 1960s provided the rational basis for dis- eases such as rhinitis,asthma and food allergy and a legitimate target for novel therapeutics.Almost 25 years were to pass before it was clearly shown that a monoclonal antibody directed against that part of the IgE molecule that is encrypted by the high- and low-affinity IgE receptors on effector cells could dra- matically remove circulating and tissue IgE by forming small com- plexes that are easily cleared without cross-linking IgE on the surface of effector cells and,therefore,failing to produce anaphy- lactic responses. The fully humanized monoclonal antibody omalizumab (Xolair™) has these properties.It has been clearly demonstrated that when administered at 2–4 weekly intervals this therapy has markedly beneficial effects on multiple outcome measures in allergic asthma. This pocketbook provides an illustrative summary of the role of IgE in asthma and allied allergic disorders and the effects of anti- IgE treatment.With little new having been introduced into the armamentarium for asthma therapy in the last three decades other than improvements in β -adrenoceptor agonists,corticos- 2 teroids and cysteinyl leukotriene antagonists,the introduction of omalizumab is likely to provide a new way of treating allergic vii disorders with effects that extend beyond a single affected organ and tissue.Its precise role in treatment guidelines will need to be carefully evaluated, but its clear efficacy and safety provide a clear statement about the importance of IgE across the full spectrum of allergic disease. Syed Hasan Arshad K Suresh Babu Stephen T Holgate March 2001 viii What is asthma and 1 allergy? What is asthma? Asthma is a chronic inflammatory disease of the airways and manifests clinically as intermittent cough and wheezing in response to exposure to allergenic and non-allergenic stimuli. The severity of asthma varies widely among individuals.In most patients the symptoms are mild and intermittent.However,in some patients it is a life-threatening disease which severely affects their quality of life. The National Heart,Lung,and Blood Institute (NHLBI)/World Health Organization (WHO) expert panel report defines asthma as (Figure 1): a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role,in particular,mast cells, eosinophils,T lymphocytes,neutrophils,and epithelial cells.In susceptible individuals,this inflammation causes recurrent episodes of wheezing,breathlessness,chest tightness,and cough, particularly at night and/or in the early morning.These symptoms are usually associated with widespread but variable airflow limitation that is at least partly reversible either spontaneously or with treatment.The inflammation also causes an associated increase in airway responsiveness to a variety of stimuli. 1
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