奥马珠单抗，抗IgE重组人源化单克隆抗体，用于治疗重度过敏性哮喘。

Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma.

作者信息

Busse W, Corren J, Lanier B Q, McAlary M, Fowler-Taylor A, Cioppa G D, van As A, Gupta N

机构信息

Department of Medicine, University of Wisconsin Hospital & Clinics, University of Wisconsin, Madison, 53792, USA.

出版信息

J Allergy Clin Immunol. 2001 Aug;108(2):184-90. doi: 10.1067/mai.2001.117880.

DOI:10.1067/mai.2001.117880

PMID:11496232

Abstract

BACKGROUND

A recombinant humanized anti-IgE mAb, omalizumab, forms complexes with free IgE, blocking its interaction with mast cells and basophils; as a consequence, it might be effective in the treatment of asthma.

OBJECTIVE

The purpose of this study was to evaluate the efficacy and safety of omalizumab in the treatment of inhaled corticosteroid-dependent asthma.

METHODS

In this phase III, double-blinded, placebo-controlled trial, 525 subjects with severe allergic asthma requiring daily inhaled corticosteroids were randomized to receive placebo or omalizumab subcutaneously every 2 or 4 weeks, depending on baseline IgE level and body weight. Inhaled corticosteroid doses were kept stable over the initial 16 weeks of treatment and tapered during a further 12-week treatment period.

RESULTS

Omalizumab treatment resulted in significantly fewer asthma exacerbations per subject and in lower percentages of subjects experiencing an exacerbation than placebo treatment during the stable steroid phase (0.28 vs 0.54 [P =.006] and 14.6% vs 23.3% [P =.009], respectively) and during the steroid reduction phase (0.39 vs 0.66 [P =.003] and 21.3% vs 32.3% [P =.004], respectively). Beclomethasone dipropionate reduction was significantly greater with omalizumab treatment than with placebo (median 75% vs 50% [P <.001]), and beclomethasone dipropionate discontinuation was more likely with omalizumab (39.6% vs 19.1% [P <.001]). Improvements in asthma symptoms and pulmonary function occurred along with a reduction in rescue beta-agonist use. Omalizumab was well tolerated, with an adverse-events profile similar to that of placebo.

CONCLUSION

The addition of omalizumab to standard asthma therapy reduces asthma exacerbations and decreases inhaled corticosteroid and rescue medication use.

摘要

背景

重组人源化抗IgE单克隆抗体奥马珠单抗可与游离IgE形成复合物，阻断其与肥大细胞和嗜碱性粒细胞的相互作用；因此，它可能对哮喘治疗有效。

目的

本研究旨在评估奥马珠单抗治疗吸入性糖皮质激素依赖型哮喘的疗效和安全性。

方法

在这项III期双盲、安慰剂对照试验中，525名需要每日吸入糖皮质激素的重度过敏性哮喘患者根据基线IgE水平和体重，随机每2周或4周皮下注射安慰剂或奥马珠单抗。在治疗的最初16周内，吸入性糖皮质激素剂量保持稳定，并在接下来的12周治疗期内逐渐减少。

结果

在稳定激素阶段（分别为0.28 vs 0.54 [P = 0.006]和14.6% vs 23.3% [P = 0.009]）以及激素减量阶段（分别为0.39 vs 0.66 [P = 0.003]和21.3% vs 32.3% [P = 0.004]），奥马珠单抗治疗导致每名受试者哮喘急性发作次数显著减少，且经历急性发作的受试者百分比低于安慰剂治疗。与安慰剂相比，奥马珠单抗治疗使二丙酸倍氯米松的减量幅度显著更大（中位数75% vs 50% [P < 0.001]），且奥马珠单抗组更有可能停用二丙酸倍氯米松（39.6% vs 19.1% [P < 0.001]）。哮喘症状和肺功能得到改善，同时急救β受体激动剂的使用减少。奥马珠单抗耐受性良好，不良事件谱与安慰剂相似。