Efficacy of soluble IL-4 receptor for the treatment of adults with asthma
Efficacy of soluble IL-4 receptor for the treatment of adults with asthma
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DOI：
10.1067/mai.2001.115624
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发表时间：
2001-06-01
影响因子：
14.2
通讯作者：
Agosti, JM
中科院分区：
文献类型：
--
作者：
Borish, LC;Nelson, HS;Agosti, JM
背景：IL-4介导哮喘重要的促炎功能，包括诱导IgE同型转换，增加血管细胞黏附分子1的表达，促进嗜酸性粒细胞跨内皮细胞迁移，刺激粘液产生和T(H)2淋巴细胞分化，导致IL-4，IL-5，IL-9和IL-13的释放。目的：本研究评价了吸入重组人可溶性白介素4受体(IL-4R)作为IL-4拮抗剂的治疗潜力。方法：本研究为随机、双盲、安慰剂对照研究，共62例受试者，每周雾化吸入0.75，1.5或3.0毫克的IL-4R或安慰剂。在筛查期间，受试者记录了对吸入皮质类固醇的依赖，这是由于每隔两周减少一到两次50%的剂量而导致的哮喘加重。结果：IL-4R耐受性良好，用药后第1秒用力呼气量下降(-0.4%，L预测值为-13%)，而服用3.0mgIL-4R组则无此现象(L预测值为-0.1%，3个月治疗期间预测值为-2%，P=0.05)。每天患者测量的晨间FEV1也显示出安慰剂组的显著下降(-0.5%L和-18%预测)，这在接受3.0mgIL-4R组中没有发生(-0.1L和-4%预测；在3个月的治疗期间P=0.02)，接受3.0mgIL-4R组(Delta 0.1)与安慰剂组(Delta 1.3超过1个月)相比，哮喘症状评分没有增加，进一步证实了IL-4R的有效性。结论：IL-4R是一种安全有效的治疗中度持续性哮喘的药物。
Background: IL-4 mediates important proinflammatory functions in asthma, including induction of the IgE isotype switch, increased expression of vascular cell adhesion molecule 1 and promotion of eosinophil transmigration across the endothelium, stimulation of mucus production, and T(H)2 Lymphocyte differentiation, leading to release of IL-4, IL-5, IL-9, and IL-13.Objective: The current study evaluated the therapeutic potential of inhaled recombinant human soluble interleukin-4 receptor (IL-4R) as an IL-4 antagonist.Methods: This study was a randomized, double-blind, placebo-controlled study in 62 subjects involving 12 once weekly nebulizations of 0.75, 1.5, or 3.0 mg of IL-4R or placebo. During screening, subjects documented dependence on inhaled corticosteroids by an exacerbation in asthma induced by one or two 50% dose reductions at 2-week intervals. After restabilization for 2 weeks on the dose above which their asthma flared, inhaled steroids were discontinued, patients were randomized, and study medication was started on day 0.Results: IL-4R was well tolerated, Efficacy was demonstrated by a decline in FEV1 observed in the placebo group (-0.4 L and -13% predicted), which did not occur in the group receiving 3.0 mg of IL-4R (-0.1 L and -2% predicted; P = .05 over the 3-month treatment period). Daily patient-measured morning FEV1 also demonstrated a significant decline in the placebo gronp (-0.5 L and -18% predicted), which did not occur in the group receiving 3.0 mg of IL-4R (-0.1 L and -4% predicted; P = .02 over the 3-month treatment period), The efficacy of IL-4R was further confirmed by the absence of increase in asthma symptom scores in the group receiving 3.0 mg of IL-4R (Delta 0.1) compared with that seen in the placebo group (Delta 1.3 over 1 month; P = .07), Study discontinuation for asthma exacerbation was not significantly different between groups (placebo, 56%; 3.0 mg of IL-4R, 47%; P = not significant).Conclusion: These promising data suggest that IL-4R is safe and effective in the treatment of moderate persistent asthma.