Stone J H, Uhlfelder M L, Hellmann D B, Crook S, Bedocs N M, Hoffman G S
Johns Hopkins University, Baltimore, Maryland, USA.
Arthritis Rheum. 2001 May;44(5):1149-54. doi: 10.1002/1529-0131(200105)44:5<1149::AID-ANR197>3.0.CO;2-F.
To evaluate the safety of etanercept (Enbrel) in patients receiving conventional treatment for Wegener's granulomatosis (WG).
We performed a 6-month open-label trial of etanercept (25 mg subcutaneously twice weekly) which was added to standard therapies for WG (glucocorticoids, methotrexate, cyclophosphamide, azathioprine, cyclosporine) and prescribed according to disease severity. Evaluations of clinical response were determined by the Birmingham Vasculitis Activity Score for WG (BVAS/WG) in 20 patients with persistently active disease or with new flares of previously established WG. Fourteen of the 20 patients (70%) had etanercept added as the only new therapeutic variable.
Injection site reactions (ISRs) were the most common adverse event related to etanercept (8 episodes in 5 patients [25%]; < 1% of all injections). All ISRs were mild. Two patients had a combined total of 5 hospitalizations (1 patient had 4), but no hospitalizations were attributable solely to etanercept-related adverse events. One patient with severe subglottic stenosis developed pneumococcal tracheobronchitis and subsequently had a localized Herpes zoster infection. Nineteen patients (95%) were still taking etanercept at 6 months, the single exception being a patient who developed progression of orbital (retro-bulbar) disease at 4 months. There were no deaths. The mean BVAS/WG at entry was 3.6 (range 1-8), which decreased at 6 months to 0.6 (P < 0.001, 95% confidence interval [95% CI] -4.0 to -2.1). Among the 14 patients in whom etanercept was the only new treatment variable, the mean daily prednisone dose decreased from 12.9 mg at entry to 6.4 mg at 6 months. This comparison did not achieve statistical significance (difference -6.5; P = 0.19, 95% CI -16.6 to +3.6). Sixteen of the patients (80%) achieved BVAS/WG scores of 0 at some point. However, intermittently active disease was observed in 15 patients (75%).
In this open-label trial, etanercept used in combination with standard treatments was well-tolerated in patients with WG. Adverse events were few. BVAS/WG scores improved at 6 months, but intermittently active WG (occasionally severe) was common. A randomized, double-masked trial to assess the efficacy of etanercept in WG has begun.
评估依那西普（恩利）在接受韦格纳肉芽肿（WG）传统治疗患者中的安全性。
我们进行了一项为期6个月的依那西普开放标签试验（皮下注射25毫克，每周两次），将其添加到WG的标准治疗方案（糖皮质激素、甲氨蝶呤、环磷酰胺、硫唑嘌呤、环孢素）中，并根据疾病严重程度进行处方。对20例持续活动性疾病或既往已确诊的WG出现新发作的患者，通过伯明翰血管炎活动评分（BVAS/WG）来评估临床反应。20例患者中有14例（70%）添加依那西普作为唯一的新治疗变量。
注射部位反应（ISR）是与依那西普相关的最常见不良事件（5例患者出现8次发作[25%]；占所有注射次数的<1%）。所有ISR均为轻度。2例患者共住院5次（1例患者住院4次），但没有住院完全归因于依那西普相关不良事件。1例严重声门下狭窄患者发生肺炎球菌气管支气管炎，随后出现局部带状疱疹感染。19例患者（95%）在6个月时仍在使用依那西普，唯一例外是1例患者在4个月时出现眼眶（球后）疾病进展。无死亡病例。入组时BVAS/WG的平均值为3.6（范围1 - 8），6个月时降至0.6（P < 0.001，95%置信区间[95%CI] -4.0至-2.1）。在依那西普作为唯一新治疗变量的14例患者中，泼尼松平均每日剂量从入组时的12.9毫克降至6个月时的6.4毫克。该比较未达到统计学显著性（差异 -6.5；P = 0.19，95%CI -16.6至+3.6）。16例患者（80%）在某些时间点BVAS/WG评分为0。然而，15例患者（75%）观察到间歇性活动性疾病。
在这项开放标签试验中，依那西普与标准治疗联合使用在WG患者中耐受性良好。不良事件较少。6个月时BVAS/WG评分有所改善，但间歇性活动性WG（偶尔严重）很常见。一项评估依那西普在WG中疗效的随机双盲试验已开始。
