Kishiyama J L, Valacer D, Cunningham-Rundles C, Sperber K, Richmond G W, Abramson S, Glovsky M, Stiehm R, Stocks J, Rosenberg L, Shames R S, Corn B, Shearer W T, Bacot B, DiMaio M, Tonetta S, Adelman D C
The Alpha Therapeutic Corporation Asthma Study Group, San Francisco, California, USA.
Clin Immunol. 1999 May;91(2):126-33. doi: 10.1006/clim.1999.4714.
To determine the efficacy of high doses of intravenous gammaglobulin (IVIG) for the treatment of severe, steroid-dependent asthma in patients between 6 and 68 years of age, a randomized, double-blind, placebo-controlled multicenter clinical trial was conducted in private and university hospitals in the United States. Patients were randomized to one of three treatment arms: 2 g IVIG/kg/month (16 patients); 1 g IVIG/kg/month (9 patients); or 2 g iv albumin (placebo)/kg/month (15 patients). The treatment consisted of seven monthly infusions followed by a posttreatment observation period. The primary outcome measurement was mean daily prednisone-equivalent dose requirements, determined during the observation month preceding initiation of treatment and compared to the month preceding the seventh infusion. Secondary clinical endpoints measured were pulmonary function, frequency of emergency room visits or hospitalizations, and number of days absent from school or work. When adjusted for body weight, the mean dose requirements fell by 33, 39, and 33% in the placebo, IVIG (1 g/kg), and IVIG (2 g/kg) treatment arms, respectively. The differences between therapies were not statistically different (P = 0.9728). The mean percentage-of-predicted FEV1 fell in all three treatment groups during the treatment period but there was no significant difference between treatment groups (P = 0.8291). There was also no significant difference in the percentage of subjects requiring emergency room visits or hospitalizations or missing days of work/school, among the three treatment groups. The trial was terminated prematurely after interim analysis determined the adverse experience rate was different between the three groups. Three patients, all randomized to the 2-g/kg IVIG dose group, were hospitalized with symptoms consistent with aseptic meningitis. In summary, in this randomized, double-blind, placebo-controlled multicenter study, high doses of IVIG did not demonstrate a clinically or statistically significant advantage over placebo (albumin) infusions for the treatment of corticosteroid-dependent asthma. Subgroup analysis failed to identify markers predicting responsiveness. High-dose IVIG can also be associated with a significant incidence of serious adverse events.
为确定大剂量静脉注射丙种球蛋白（IVIG）治疗6至68岁严重依赖类固醇哮喘患者的疗效，在美国私立和大学医院开展了一项随机、双盲、安慰剂对照的多中心临床试验。患者被随机分为三个治疗组之一：2 g IVIG/（kg·月）（16例患者）；1 g IVIG/（kg·月）（9例患者）；或2 g静脉注射白蛋白（安慰剂）/（kg·月）（15例患者）。治疗包括每月输注7次，随后是治疗后观察期。主要结局指标是每日泼尼松等效剂量的平均需求，在开始治疗前的观察月确定，并与第七次输注前的月份进行比较。测量的次要临床终点是肺功能、急诊就诊或住院频率以及缺勤或旷工天数。调整体重后，安慰剂组、IVIG（1 g/kg）组和IVIG（2 g/kg）组的平均剂量需求分别下降了33%、39%和33%。各治疗组之间的差异无统计学意义（P = 0.9728）。在治疗期间，所有三个治疗组的预计FEV1平均百分比均下降，但各治疗组之间无显著差异（P = 0.8291）。三个治疗组之间，在需要急诊就诊或住院的受试者百分比或缺勤/旷工天数方面也无显著差异。在中期分析确定三组不良事件发生率不同后，该试验提前终止。三名均被随机分配至2 g/kg IVIG剂量组的患者因与无菌性脑膜炎一致的症状住院。总之，在这项随机、双盲、安慰剂对照的多中心研究中，大剂量IVIG在治疗依赖皮质类固醇哮喘方面，未显示出比安慰剂（白蛋白）输注在临床或统计学上的显著优势。亚组分析未能识别出预测反应性的标志物。大剂量IVIG还可能与严重不良事件的高发生率相关。
