用单克隆抗IgE抗体治疗过敏性哮喘。重组人源化抗IgE单克隆抗体（rhuMAb-E25）研究组。

Treatment of allergic asthma with monoclonal anti-IgE antibody. rhuMAb-E25 Study Group.

作者信息

Milgrom H, Fick R B, Su J Q, Reimann J D, Bush R K, Watrous M L, Metzger W J

机构信息

Department of Pediatrics, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, USA.

出版信息

N Engl J Med. 1999 Dec 23;341(26):1966-73. doi: 10.1056/NEJM199912233412603.

DOI:10.1056/NEJM199912233412603

PMID:10607813

Abstract

BACKGROUND

Immune responses mediated by IgE are important in the pathogenesis of allergic asthma. A recombinant humanized monoclonal antibody (rhuMAb-E25) forms complexes with free IgE and blocks its interaction with mast cells and basophils. We studied the efficacy of rhuMab-E25 as a treatment for moderate-to-severe allergic asthma.

METHODS

After a 4-week run-in period, we randomly assigned 317 subjects (age range, 11 to 50 years) who required inhaled or oral corticosteroids (or both) to receive either placebo or one of two regimens of rhuMAB-E25: high-dose rhuMAb-E25 (5.8 microg per kilogram of body weight per nanogram of IgE per milliliter or low-dose rhuMAb-E25 (2.5 microg per kilogram per nanogram of IgE per milliliter) intravenously on days 0 (half a dose), 4 (half a dose), and 7 (full dose) and then once every 2 weeks thereafter for 20 weeks. For the first 12 weeks of the study, the subjects continued the regimen of corticosteroids they had received before enrollment. During the following eight weeks, the doses of corticosteroids were tapered in an effort to discontinue this therapy. The primary outcome measure was an improvement in the asthma symptom score at 12 weeks, according to a 7-point scale, in which a score of 1 indicated no symptoms and a score of 7 the most severe symptoms.

RESULTS

A total of 106 subjects were assigned to receive a high dose of rhuMAb-E25, 106 were assigned to receive a low dose, and 105 were assigned to receive placebo. At base line, the mean asthma symptom score was 4.0. After 12 weeks of therapy, the mean (+/-SE) scores were 2.8+/-0.1 in the high-dose group (P=0.008) and 2.8+/-0.1 in the low-dose group (P=0.005), as compared with 3.8+/-0.1 in the placebo group. At 20 weeks, the mean scores were 2.7+/-0.1 in both the high-dose group (P=0.048) and the low-dose group (P=0.14), as compared with 2.9+/-0.1 in the placebo group. More subjects in the two rhuMAb-E25 groups were able to decrease or discontinue their use of corticosteroids than in the placebo group, but only some of the differences were significant. After 20 weeks, serum free IgE concentrations decreased by a mean of more than 95 percent in both rhuMAb-E25 groups. The therapy was well tolerated. After 20 weeks, none of the subjects had antibodies against rhuMAb-E25.

CONCLUSIONS

A recombinant humanized monoclonal antibody directed against IgE has potential as a treatment for subjects with moderate or severe allergic asthma.

摘要

背景

IgE介导的免疫反应在过敏性哮喘的发病机制中起重要作用。重组人源化单克隆抗体（rhuMAb-E25）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。我们研究了rhuMab-E25治疗中重度过敏性哮喘的疗效。

方法

在为期4周的导入期后，我们将317名需要吸入或口服皮质类固醇（或两者都用）治疗的受试者（年龄范围为11至50岁）随机分为接受安慰剂或两种rhuMAB-E25治疗方案之一：高剂量rhuMAb-E25（每千克体重每纳克IgE每毫升5.8微克）或低剂量rhuMAb-E25（每千克体重每纳克IgE每毫升2.5微克），于第0天（半剂量）、第4天（半剂量）和第7天（全剂量）静脉注射，此后每2周注射一次，共20周。在研究的前12周，受试者继续使用入组前接受的皮质类固醇治疗方案。在接下来的8周内，逐渐减少皮质类固醇的剂量，以停用该治疗。主要结局指标是12周时哮喘症状评分的改善情况，采用7分制，1分表示无症状，7分表示症状最严重。

结果

共106名受试者被分配接受高剂量rhuMAb-E25，106名接受低剂量，105名接受安慰剂。基线时，平均哮喘症状评分为4.0。治疗12周后，高剂量组的平均（±SE）评分为2.8±0.1（P=0.008），低剂量组为2.8±0.1（P=0.005），而安慰剂组为3.8±0.1。在20周时，高剂量组（P=0.048）和低剂量组（P=0.14）的平均评分均为2.7±0.1，而安慰剂组为2.9±0.1。与安慰剂组相比，两个rhuMAb-E25组中更多的受试者能够减少或停用皮质类固醇，但只有部分差异具有统计学意义。20周后，两个rhuMAb-E25组的血清游离IgE浓度平均下降超过95%。该治疗耐受性良好。20周后，没有受试者产生针对rhuMAb-E25的抗体。