Holgate S, Bousquet J, Wenzel S, Fox H, Liu J, Castellsague J
RCMB Research Division, Southampton General Hospital, UK.
Curr Med Res Opin. 2001;17(4):233-40.
Add-on therapy with omalizumab, an anti-immunoglobulin E antibody, is effective in improving disease control in patients with allergic asthma of varying severity. The aim of the present study was to determine the efficacy of omalizumab in a subgroup of patients at high risk of serious asthma-related morbidity and mortality.
A meta-analysis was performed of three randomised, double-blind, placebo-controlled studies (studies 1, 2 and 3) that enrolled 1412 patients with moderate or severe allergic asthma, all requiring daily treatment with inhaled corticosteroids (ICS). Omalizumab was administered subcutaneously every 2 or 4 weeks at a total 4-weekly dose of at least 0.016 mg/kg/IgE [IU/ml]. Each study consisted of a 16-week steroid-stable phase and a 12-16-week steroid-reduction phase, followed by a 24-week extension phase (studies 1 and 2 only). The primary outcome measure was the annualised rate of significant asthma exacerbation episodes (sAEEs) during the steroid-stable phase for the pooled subgroup of 254 high-risk patients (omalizumab, n = 135; placebo, n = 119). sAEEs were those requiring a doubling of baseline ICS dose (studies 1 and 2 only) or use of systemic steroids (all three studies).
Overall, the number of patients with at least one sAEE during the steroid-stable phase was reduced from 35% (42/119) with placebo to 18% (24/135) with omalizumab. Mean sAEE rates were 1.56 and 0.69 per patient-year, respectively, a reduction of 56% with omalizumab (p = 0.007). Similar reductions in exacerbations in favour of omalizumab were observed for the whole study period and for all AEEs. In those with a history of hospitalisation in the last year, 6/49 (12%) on placebo vs. 2/44 (4.5%) on omalizumab were re-hospitalised during the study period. Patients treated with omalizumab also showed significantly greater improvements from baseline in PEFR (p = 0.026), overall AQoL (p = 0.042) and mean nocturnal (p = 0.007) and mean total (p = 0.011) asthma symptom scores compared with placebo.
In patients at high risk of serious asthma-related morbidity and mortality, treatment with omalizumab offers the potential to halve the rate of asthma exacerbations and improve disease control.
奥马珠单抗是一种抗免疫球蛋白E抗体，附加使用该药物对不同严重程度的过敏性哮喘患者有效改善疾病控制。本研究的目的是确定奥马珠单抗在有严重哮喘相关发病和死亡高风险的亚组患者中的疗效。
对三项随机、双盲、安慰剂对照研究（研究1、2和3）进行荟萃分析，这些研究纳入了1412例中度或重度过敏性哮喘患者，所有患者均需要每日吸入糖皮质激素（ICS）治疗。奥马珠单抗每2或4周皮下注射一次，每4周总剂量至少为0.016mg/kg/IgE[IU/ml]。每项研究包括一个16周的激素稳定期和一个12 - 16周的激素减量期，随后是一个24周的延长期（仅研究1和2）。主要结局指标是254例高风险患者合并亚组在激素稳定期的严重哮喘加重发作年化率（sAEEs）（奥马珠单抗组，n = 135；安慰剂组，n = 119）。sAEEs是指需要将基线ICS剂量加倍（仅研究1和2）或使用全身性激素（所有三项研究）的发作。
总体而言，在激素稳定期至少有一次sAEE的患者数量从安慰剂组的3 / 5（42/119）降至奥马珠单抗组的18%（24/135）。平均sAEE率分别为每人年1.56次和0.69次，奥马珠单抗组降低了56%（p = 0.007）。在整个研究期间和所有哮喘加重发作中，均观察到有利于奥马珠单抗的类似加重发作减少情况。在过去一年有住院史的患者中，安慰剂组49例中有6例（12%）在研究期间再次住院，而奥马珠单抗组44例中有2例（4.5%）再次住院。与安慰剂相比，接受奥马珠单抗治疗的患者在PEFR（p = 0.026）、总体AQoL（p = 0.042）以及平均夜间（p = 0.007）和平均总（p = 0.０１１）哮喘症状评分方面从基线的改善也显著更大。
在有严重哮喘相关发病和死亡高风险的患者中，使用奥马珠单抗治疗有可能使哮喘加重率减半并改善疾病控制。
