Department of Pediatric Allergy, Pneumology and Cystic Fibrosis, University Children's Hospital, J.W. Goethe University, Frankfurt, Germany.
Int Arch Allergy Immunol. 2013;160(1):102-10. doi: 10.1159/000339243. Epub 2012 Aug 28.
Omalizumab has been shown to suppress responses to inhaled allergens in allergic asthma patients with pretreatment immunoglobulin E (IgE) ≤700 IU/ml. To extend current dosing tables, we evaluated the potential of high omalizumab doses to block allergen-induced bronchoconstriction in patients with higher IgE levels.
Asthmatic adults (18-65 years; body weight 40-150 kg) were divided into groups according to screening IgE (group 1: 30-300 IU/ml; group 2: 700-2,000 IU/ml) and randomized 2:1 to omalizumab/placebo every 2 or 4 weeks for 12-14 weeks. Allergen bronchoprovocation (ABP) testing was performed before treatment and at weeks 8 and 16. The primary efficacy endpoint, the early-phase allergic response (EAR), was defined as the maximum percentage drop in forced expiratory volume in 1 s during the first 30 min after ABP. Serum free IgE was determined as a pharmacodynamic endpoint, and the exhaled fractional concentration of nitric oxide (FE(NO)) was an exploratory endpoint.
Fifty patients were included in the study. Omalizumab improved EAR; at week 8, EAR was 23.1% for placebo, 9.3% in group 1 (p = 0.018 versus placebo) and 5.6% in group 2 (p < 0.001). At week 16, EAR was 20%, 11.8% (p = 0.087) and 5.1% (p < 0.001), respectively. Free IgE decreased in groups 1 and 2 and remained <50 ng/ml in all patients during weeks 6-16. Omalizumab completely suppressed FE(NO) increases after ABP in both groups.
Omalizumab blocked early asthmatic responses over a broad range of IgE/body weight combinations. Extending the dosing tables enables omalizumab to benefit a wider range of patients.
奥马珠单抗已被证明可抑制预处理免疫球蛋白 E（IgE）≤700IU/ml 的过敏性哮喘患者对吸入性过敏原的反应。为了扩展当前的剂量表，我们评估了高剂量奥马珠单抗阻断 IgE 水平较高的患者过敏原诱导的支气管收缩的潜力。
将成年哮喘患者（18-65 岁；体重 40-150kg）根据筛选时的 IgE（组 1：30-300IU/ml；组 2：700-2000IU/ml）分为两组，并按 2:1 随机分配接受奥马珠单抗/安慰剂，每 2 或 4 周治疗 12-14 周。在治疗前和第 8 周和第 16 周进行过敏原支气管激发试验（ABP）。主要疗效终点为早期过敏反应（EAR），定义为 ABP 后 30 分钟内用力呼气量的最大百分比下降。血清游离 IgE 作为药效学终点，呼气一氧化氮分数（FE（NO））作为探索性终点。
共纳入 50 例患者。奥马珠单抗改善 EAR；第 8 周时，安慰剂组 EAR 为 23.1%，组 1 为 9.3%（p=0.018 与安慰剂相比），组 2 为 5.6%（p<0.001）。第 16 周时，EAR 分别为 20%、11.8%（p=0.087）和 5.1%（p<0.001）。组 1 和 2 中的游离 IgE 减少，所有患者在第 6-16 周期间游离 IgE 均<50ng/ml。奥马珠单抗完全抑制了两组中 ABP 后 FE（NO）的增加。
奥马珠单抗在广泛的 IgE/体重组合范围内阻断了早期哮喘反应。扩展剂量表使奥马珠单抗能够使更多的患者受益。
