Efficacy and safety of a recombinant anti‐immunoglobulin E antibody (omalizumab) in severe allergic asthma

Clinical and Experimental Allergy - Tập 34 Số 4 - Trang 632-638 - 2004
Stephen T. Holgate1, Chuchalin Ag2, Jean‐Louis Hébert3, Jan Lötvall4, G. Persson5, Kian Fan Chung6, Jean Bousquet6, Huib A.M. Kerstjens7, Helen Fox8, J. Thirlwell8, Giovanni Della Cioppa8
1Southampton General Hospital, Southampton UK
2Research Institute of Pulmonology, Moscow, Russia
3CRAAQ, Place de la Cite, Ste-Foy, Quebec, Canada
4Lungfarmakologiska Gruppen, Göteborgs Universitet, Göteborg, Sweden
5Proevningsenheten, Farmakologiska Kliniken, Lund, Sweden
6National Heart & Lung Institute, London, UK
7University Hospital Gröningen, Gröningen, The Netherlands
8Novartis Horsham Research Centre, Horsham, UK

Tóm tắt

SummaryBackground Patients with severe asthma are often inadequately controlled on existing anti‐asthma therapy, constituting an unmet clinical need.Objective This randomized, double‐blind, placebo‐controlled trial evaluated the ability of omalizumab, a humanized monoclonal anti‐IgE antibody, to improve disease control sufficiently to enable inhaled corticosteroid reduction in patients with severe allergic asthma.Methods After a run‐in period when an optimized fluticasone dose (1000 μg/day) was received for 4 weeks, patients were randomized to receive subcutaneous omalizumab [minimum 0.016 mg/kg/IgE (IU/mL) per 4 weeks; n=126] or matching placebo (n=120) at intervals of 2 or 4 weeks. The study comprised a 16‐week add‐on phase of treatment followed by a 16‐week fluticasone‐reduction phase. Short‐/long‐acting β2‐agonists were allowed as needed.Results Median reductions in fluticasone dose were significantly greater with omalizumab than placebo: 60% vs. 50% (P=0.003). Some 73.8% and 50.8% of patients, respectively, achieved a 50% dose reduction (P=0.001). Fluticasone dose reduction to 500 μg/day occurred in 60.3% of omalizumab recipients vs. 45.8% of placebo‐treated patients (P=0.026). Through both phases, omalizumab reduced rescue medication requirements, improved asthma symptoms and asthma‐related quality of life compared to placebo.Conclusion Omalizumab treatment improves asthma control in severely allergic asthmatics, reducing inhaled corticosteroid requirements without worsening of symptom control or increase in rescue medication use.

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Tài liệu tham khảo

10.1183/09031936.98.12061322

Chung KF, 1999, Difficult/therapy‐resistant asthma, the need for an integrated approach to define clinical phenotypes, evaluate risk factors, understand pathophysiology and find novel therapies, 13, 1198

Holt PG, 1999, The role of allergy in the development of asthma, Nature, 402, B12, 10.1038/35037009

10.1111/j.1365-2222.1989.tb02408.x

10.1038/35037000

Presta LG, 1993, Humanization of an antibody directed against IgE, J Immunol, 151, 2623, 10.4049/jimmunol.151.5.2623

10.1021/bi9928391

10.1159/000237010

10.1021/bi00033a020

10.1172/JCI119252

10.1164/ajrccm.155.6.9196082

10.1164/ajrccm.155.6.9196083

Fox JA, 1996, Tissue distribution and complex formation with IgE of an anti‐IgE antibody after intravenous administration in cynomolgus monkeys, J Pharmacol Exp Ther, 279, 1000

10.1067/mai.2001.116434

10.1067/mai.2001.117880

10.1183/09031936.01.00092101

10.1542/peds.108.2.e36

10.1164/ajrccm/147.4.832

10.1016/0895-4356(94)90036-1

10.1136/bmj.316.7132.690

Agresti A., 1996, An introduction to categorical data analysis, version 6

SAS/STAT, 1990, SAS/STAT user's guide

10.1056/NEJM199912233412603

10.1067/mai.2001.111593

10.1001/jama.286.23.2956

10.1067/mai.2000.108310

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Clinical and Experimental Allergy

Tập 34 Số 4

632-638

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