Limited versus severe Wegener's granulomatosis - Baseline data on patients in the Wegener's granulomatosis etanercept trial
Limited versus severe Wegener's granulomatosis - Baseline data on patients in the Wegener's granulomatosis etanercept trial
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DOI：
10.1002/art.11075
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发表时间：
2003-08-01
影响因子：
--
通讯作者：
White, B
中科院分区：
文献类型：
--
作者：
Hopkins, J;Stone, JH;White, B
目标。目的：报告参加依那西普试验（WGET）的180例韦格纳肉芽肿病（WG）患者的基线数据，并检查有限疾病患者和严重疾病患者的人口统计学和临床差异。有限疾病和严重疾病的定义在试验前会议上经研究人员一致同意，并作为分层标准纳入方案。基于临床特征和根据疾病活动度对患者进行治疗的意向，这些数据被前瞻性地应用于WGET患者队列。与疾病发病、诊断日期、临床特征、抗中性粒细胞细胞质抗体测定、组织活检结果和其他病史相关的数据收集在基线病史表上。每个中心的医师调查员都参与了该表格的开发，并且在试验开始前都获得了使用该表格的认证。筛选试验但未入组的患者的数据也被收集。在有限疾病和严重疾病亚群之间观察到几个显著差异。病情有限的患者发病时比病情严重的患者年轻近10岁。患有严重疾病的患者中有33%是女性，相比之下，患有有限疾病的患者中有58%是女性。尽管出现症状时年龄较轻，但病情有限的患者往往病程较长，在一段缓解期后既往疾病加重的可能性较大，并且在入组时破坏性上呼吸道疾病（例如，鞍鼻畸形）的患病率较高。与患有严重疾病的患者相比，有限的WG患者不太可能有蛋白酶3或髓过氧化物酶抗体。病情严重的患者既往甲状腺疾病的可能性更高，特别是Graves病或桥本甲状腺炎，提示这些疾病亚群中可能存在不同的发病因素。这些亚群之间观察到的其他差异，如严重疾病组肺泡出血的频率更高，与局限性疾病和严重疾病的先验定义有关。在性别、年龄、疾病复发的可能性、某些器官系统损伤的风险以及可能的病因因素方面，局限性WG患者与重度WG患者存在显著差异。患者亚群的这些差异（可能还有其他目前未被认识到的差异）可能对发病机制、预后、对治疗的反应以及未来临床研究的设计产生影响。
Objective. To report baseline data on 180 patients with Wegener's granulomatosis (WG) enrolled in the WG Etanercept Trial (WGET), and to examine demographic and clinical differences between patients with limited disease and those with severe disease.Methods. Definitions of limited and severe disease were agreed upon by consensus of the investigators at a pretrial meeting and were incorporated into the protocol as a stratification criterion. These data were applied prospectively to the WGET patient cohort, based on clinical features and the intention to treat patients according to disease activity. Data related to disease onset, date of diagnosis, clinical features, antineutrophil cytoplasmic antibody assays, tissue biopsy findings, and other medical history were collected on a baseline medical history form. Physician-investigators from each center participated in the development of this form, and all were certified in its use prior to the start of the trial. Selected data on patients who were screened for the trial but were not enrolled were also collected.Results. Several significant differences between the limited and severe disease subsets were observed. Patients with limited disease were nearly a decade younger at disease onset compared with patients with severe disease. Thirty-three percent of patients with severe disease were women, compared with 58% of those with limited disease. Despite their younger age at symptom onset, patients with limited disease tended to have longer disease duration, a greater likelihood of experiencing exacerbation of previous disease following a period of remission, and a higher prevalence of destructive upper respiratory tract disorders at the time of enrollment (e.g., saddle-nose deformity). Patients with limited WG were less likely than those with severe disease to,have antibodies to either proteinase 3 or myeloperoxidase. Patients with severe disease had a higher likelihood of previous thyroid disease, particularly either Graves' disease or Hashimoto thyroiditis, suggesting the possibility of different pathogenetic factors within these disease subsets. Other observed differences between these subsets, such as the greater frequency of alveolar hemorrhage in the severe disease group, were related to the a priori definitions of limited and severe disease.Conclusion. There are significant differences between patients with limited WG and those with severe WG with regard to sex, age, the likelihood of recurrent disease, the risk of damage in certain organ systems, and, possibly, etiologic factors. These differences (and perhaps other differences that are currently unrecognized) in patient subsets may have implications for mechanisms of pathogenesis, prognosis, response to treatment, and the design of future clinical investigations.