Holgate S T, Chuchalin A G, Hébert J, Lötvall J, Persson G B, Chung K F, Bousquet J, Kerstjens H A, Fox H, Thirlwell J, Cioppa G Della
RCMB Research Division, Southampton General Hospital, Southampton, UK.
Clin Exp Allergy. 2004 Apr;34(4):632-8. doi: 10.1111/j.1365-2222.2004.1916.x.
Patients with severe asthma are often inadequately controlled on existing anti-asthma therapy, constituting an unmet clinical need.
This randomized, double-blind, placebo-controlled trial evaluated the ability of omalizumab, a humanized monoclonal anti-IgE antibody, to improve disease control sufficiently to enable inhaled corticosteroid reduction in patients with severe allergic asthma.
After a run-in period when an optimized fluticasone dose (> or =1000 microg/day) was received for 4 weeks, patients were randomized to receive subcutaneous omalizumab [minimum 0.016 mg/kg/IgE (IU/mL) per 4 weeks; n=126] or matching placebo (n=120) at intervals of 2 or 4 weeks. The study comprised a 16-week add-on phase of treatment followed by a 16-week fluticasone-reduction phase. Short-/long-acting beta(2)-agonists were allowed as needed.
Median reductions in fluticasone dose were significantly greater with omalizumab than placebo: 60% vs. 50% (P=0.003). Some 73.8% and 50.8% of patients, respectively, achieved a > or =50% dose reduction (P=0.001). Fluticasone dose reduction to < or =500 microg/day occurred in 60.3% of omalizumab recipients vs. 45.8% of placebo-treated patients (P=0.026). Through both phases, omalizumab reduced rescue medication requirements, improved asthma symptoms and asthma-related quality of life compared to placebo.
Omalizumab treatment improves asthma control in severely allergic asthmatics, reducing inhaled corticosteroid requirements without worsening of symptom control or increase in rescue medication use.
重度哮喘患者常常无法通过现有的抗哮喘治疗得到充分控制，这是一个尚未满足的临床需求。
这项随机、双盲、安慰剂对照试验评估了人源化抗IgE单克隆抗体奥马珠单抗充分改善疾病控制，从而使重度过敏性哮喘患者能够减少吸入性糖皮质激素用量的能力。
在经过4周的导入期，接受优化剂量（≥1000微克/天）的氟替卡松治疗后，患者被随机分组，每2周或4周接受一次皮下注射奥马珠单抗[最低0.016毫克/千克/每4周IgE（国际单位/毫升）；n = 126]或匹配的安慰剂（n = 120）。该研究包括一个为期16周的附加治疗阶段，随后是一个为期16周的氟替卡松减量阶段。根据需要可使用短效/长效β2受体激动剂。
奥马珠单抗组氟替卡松剂量的中位数降低幅度显著大于安慰剂组：分别为60%和50%（P = 0.003）。约73.8%和50.8%的患者分别实现了≥50%的剂量降低（P = 0.001）。60.3%接受奥马珠单抗治疗的患者氟替卡松剂量降至≤500微克/天，而接受安慰剂治疗的患者为45.8%（P = 0.026）。在两个阶段中，与安慰剂相比，奥马珠单抗均减少了急救药物的需求，改善了哮喘症状和哮喘相关的生活质量。
奥马珠单抗治疗可改善重度过敏性哮喘患者的哮喘控制，减少吸入性糖皮质激素用量，且不会使症状控制恶化或增加急救药物的使用。
