Bousquet Jean, Wenzel Sally, Holgate Stephen, Lumry William, Freeman Peter, Fox Howard
Service de Pneumologie, Hôpital Arnaud de Villeneuve, Montpellier, France.
Chest. 2004 Apr;125(4):1378-86. doi: 10.1378/chest.125.4.1378.
To determine baseline characteristics predictive of response to omalizumab, an anti-IgE antibody, in patients with allergic asthma.
Pooled analysis of two multicenter, double-blind, randomized, placebo-controlled phase III studies with omalizumab.
One thousand seventy allergic asthma patients symptomatic despite moderate-to-high doses (mean, 725 micro g/d) of inhaled beclomethasone dipropionate (BDP).
Omalizumab (n = 542) or placebo (n = 528) were administered at a 4-weekly subcutaneous dose of at least 0.016 mg/kg/IgE (IU/mL) for 16 weeks in addition to stable BDP therapy.
Univariate logistic regression was performed to explore baseline variables predictive of best response. Various aspects of response (reduced symptom scores, reduced usage of rescue medication, improved lung function, improved quality of life [QoL]) were explored as well as a composite definition of response (response in at least one of these four aspects with no asthma exacerbation during 16 weeks of treatment). Time to onset of response as well as the ability to predict eventual response were also determined for the composite definition of response. A consistent pattern of predictive covariates was seen over all definitions of response (except for QoL). For the composite definition, a history of emergency asthma treatment in the past year was the factor most predictive (p = 0.015) of best response on active treatment (response rate for those with such history was 67% for omalizumab and 42% for placebo; for those without a history the response rates were 63% and 54%, respectively). Another factor predictive of best response on active treatment was high BDP dose (p = 0.037; response rate for those treated with >or= 800 micro g/d was 65% for omalizumab and 40% for placebo; for those treated with < 800 micro g/d, the response rates were 63% and 55%, respectively). A low FEV(1) was also predictive (p = 0.072; response rates for those with FEV(1) <or= 65% predicted were 60% for omalizumab and 40% for placebo; for those with FEV(1) >or= 65% predicted, the response rates were 67% and 53%, respectively). Seventy-six percent of patients had at least one of these factors. This subgroup showed odds of being a responder (composite definition) 2.25 times higher (95% confidence interval, 1.68 to 3.01) than placebo. Some 38% of patients treated with omalizumab showed a response (composite definition) at the first evaluation time point at 4 weeks, increasing to 64% at week 16 (vs 48% for placebo; p < 0.001). Among omalizumab responders at 16 weeks, only 61% had responded at 4 weeks whereas 87% had responded at 12 weeks.
Patients who benefit most when omalizumab is administered as add-on therapy are those receiving high doses of BDP, those with a history of frequent emergency asthma treatment, and those with poor lung function. Patients should be treated with omalizumab for a minimum duration of 12 weeks.
确定过敏性哮喘患者中预测抗IgE抗体奥马珠单抗疗效的基线特征。
对两项使用奥马珠单抗的多中心、双盲、随机、安慰剂对照III期研究进行汇总分析。
1070例过敏性哮喘患者，尽管吸入了中高剂量（平均725μg/d）的二丙酸倍氯米松（BDP）仍有症状。
除稳定的BDP治疗外，奥马珠单抗组（n = 542）或安慰剂组（n = 528）每4周皮下注射一次，剂量至少为0.016mg/kg/IgE（IU/mL），共16周。
进行单因素逻辑回归以探索预测最佳疗效的基线变量。研究了疗效的各个方面（症状评分降低、急救药物使用减少、肺功能改善、生活质量[QoL]改善）以及疗效的综合定义（在治疗的16周内这四个方面中至少有一个方面有改善且无哮喘加重）。还确定了综合疗效定义的起效时间以及预测最终疗效的能力。在所有疗效定义中（除生活质量外）均观察到一致的预测协变量模式。对于综合疗效定义，过去一年有紧急哮喘治疗史是活性治疗最佳疗效的最具预测性因素（p = 0.015）（有该病史者奥马珠单抗的有效率为67%，安慰剂为42%；无该病史者有效率分别为63%和54%）。活性治疗最佳疗效的另一个预测因素是高BDP剂量（p = 0.037；接受≥800μg/d治疗者奥马珠单抗的有效率为65%，安慰剂为40%；接受<800μg/d治疗者有效率分别为63%和55%）。低FEV₁也具有预测性（p = 0.072；FEV₁≤预计值65%者奥马珠单抗的有效率为60%，安慰剂为40%；FEV₁≥预计值65%者有效率分别为67%和53%）。76%的患者至少有这些因素之一。该亚组成为有效者（综合定义）的几率比安慰剂高2.25倍（95%置信区间，1.68至3.01）。约38%接受奥马珠单抗治疗的患者在第4周的首次评估时间点显示有疗效（综合定义），在第16周增至64%（安慰剂为48%；p < 0.001）。在第16周时奥马珠单抗治疗有效的患者中，只有61%在第4周时有效，而87%在第12周时有效。
奥马珠单抗作为附加治疗时获益最大的患者是接受高剂量BDP治疗者、有频繁紧急哮喘治疗史者以及肺功能差者。患者使用奥马珠单抗治疗的最短持续时间应为12周。
