Bernstein I L, Bernstein D I, Dubb J W, Faiferman I, Wallin B
University of Cincinnati College of Medicine, Department of Medicine, OH 45267, USA.
J Allergy Clin Immunol. 1996 Aug;98(2):317-24. doi: 10.1016/s0091-6749(96)70156-2.
Previous clinical studies have demonstrated that injectable gold salts and the oral gold compound, auranofin, possess significant steroid-sparing effects in the treatment of asthma.
The objectives of this investigation were to determine whether auranofin could reduce oral corticosteroid requirements and to evaluate the safety of auranofin in the treatment of chronic corticosteroid-dependent asthma.
Patients with asthma were eligible if they required at least 10 mg of prednisone per day for control and prevention of asthma exacerbations. Two hundred seventy-nine patients with chronic corticosteroid-dependent asthma (requiring > or = 10 mg/day) were randomized to receive auranofin, 3 mg twice daily, or placebo during an 8-month clinical trial, which was divided into three phases including: a 4-week baseline period (phase I), a 6-month double-blind treatment and steroid reduction period (phase II), and a 4-week posttreatment observation period during which steroid and auranofin doses or placebo doses were maintained at levels achieved by the end of phase II (phase III). The primary efficacy variable was "therapeutic success" or reduction of daily corticosteroid use by 50% or more.
The proportion of patients in the auranofin group achieving therapeutic success (41%) was significantly higher than that in the placebo group (27%) (p = 0.01). This effect was greatest in patients requiring 10 to 19 mg of oral prednisone per day at baseline (p < 0.001). In all treated patients, including those who did and did not complete the trial, significant reduction (> or = 50% of baseline) in oral corticosteroid dosage was achieved in the auranofin group (60%) compared with the placebo group (32%) (p < 0.001). There were no significant differences between treatment groups in symptoms, concomitant medication use, or lung function. Mean serum total IgE levels decreased significantly from baseline in the auranofin group (-44.63 IU/ml) compared with the placebo group (p = 0.001). Gastrointestinal and cutaneous adverse events were greater in the auranofin group.
Auranofin demonstrated a steroid-sparing effect without concomitant worsening of symptoms or lung function and appeared to be more effective in patients dependent on 10 to 19 mg of prednisone per day. Therefore this study has demonstrated that auranofin is useful as a steroid-sparing agent in the treatment of chronic corticosteroid-dependent asthma.
先前的临床研究表明，注射用金盐和口服金化合物金诺芬在哮喘治疗中具有显著的激素节省作用。
本研究的目的是确定金诺芬是否能减少口服皮质类固醇的用量，并评估金诺芬治疗慢性皮质类固醇依赖型哮喘的安全性。
如果哮喘患者每天至少需要10毫克泼尼松来控制和预防哮喘发作，则符合入选条件。279例慢性皮质类固醇依赖型哮喘患者（每天需要≥10毫克）在一项为期8个月的临床试验中被随机分为两组，分别接受每日两次、每次3毫克的金诺芬治疗或安慰剂治疗。该试验分为三个阶段，包括：为期4周的基线期（第一阶段）、为期6个月的双盲治疗和激素减量期（第二阶段），以及为期4周的治疗后观察期，在此期间，激素和金诺芬剂量或安慰剂剂量维持在第二阶段结束时达到的水平（第三阶段）。主要疗效变量为“治疗成功”，即每日皮质类固醇用量减少50%或更多。
金诺芬组达到治疗成功的患者比例（41%）显著高于安慰剂组（27%）（p = 0.01）。这种效果在基线时每天需要10至19毫克口服泼尼松的患者中最为明显（p < 0.001）。在所有接受治疗的患者中，包括那些完成和未完成试验的患者，金诺芬组口服皮质类固醇剂量显著降低（≥基线的50%）的比例为60%，而安慰剂组为32%（p < 0.001）。治疗组在症状、伴随用药或肺功能方面没有显著差异。与安慰剂组相比，金诺芬组的平均血清总IgE水平从基线显著下降（-44.63 IU/ml）（p = 0.001）。金诺芬组的胃肠道和皮肤不良事件较多。
金诺芬显示出激素节省作用，且症状或肺功能没有随之恶化，并且在每天依赖10至19毫克泼尼松的患者中似乎更有效。因此，本研究表明金诺芬作为一种激素节省剂在治疗慢性皮质类固醇依赖型哮喘中是有用的。
