Granulomatosis with polyangiitis (GPA) is small vessel vasculitis with heterogeneous clinical presentation. In the present population-based cohort study, we classified patients with GPA based on clinical features at presentation using an unsupervised clustering approach and compared their mortality, infections and frequency of comorbidities. In this open cohort study, de-identified primary care data of patients with GPA included in the IQVIA Medical Research Data database between 1 January 1995 and 25 September 2019 was analysed retrospectively. Latent class analysis was performed to create symptom clusters of patients based on 16 categories of symptoms representing various organ involvement. All-cause mortality of resultant clusters was compared after adjusting for age, sex, Townsend deprivation quintile and smoking status at index date using extended Cox proportional hazards models. Prescription of antibiotics, considered as an indirect indicator of recurrent bacterial infection, was compared using a recurrent event model, after adjusting for quarterly use of steroid as a time-dependent covariate. Cumulative frequencies of common comorbidities were compared among the clusters at index visit, 1-year and 3-year follow-up. Altogether, 649 patients with GPA [median age 60.0 (IQR: 49.6–70.1)] were included. Three clusters were identified: patients with limited disease mainly with involvement of ENT and cough were classified into cluster 1 (n = 426); cluster 2 had generalised non-renal disease (n = 176); while patients in cluster 3 had renal-predominant disease (n = 47). Many patients in cluster 1 developed generalised disease at the end of 1 year. Mortality in clusters 2 and 3 was higher compared with cluster 1. Mortality in cluster 1 itself was 68% higher than the general population without GPA. The duration of antibiotics prescription and frequency of coexisting medical illnesses was also higher in clusters 2 and 3. In a primary care setting, patients with GPA can be classified into three distinct clusters with different prognosis, susceptibility to recurrent infections and presence of comorbidities. The tendency of cluster 1 to evolve into a more generalised disease raises questions about current immunosuppressive treatment approaches in these patients.

中文翻译：

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基于临床表现症状的肉芽肿性多血管炎 (GPA) 患者的聚类分析：一项基于英国人群的队列研究

肉芽肿性多血管炎（GPA）是临床表现异质的小血管炎。在目前基于人群的队列研究中，我们使用无监督聚类方法根据临床特征对 GPA 患者进行分类，并比较他们的死亡率、感染和合并症频率。在这项开放队列研究中，对 1995 年 1 月 1 日至 2019 年 9 月 25 日期间 IQVIA 医学研究数据数据库中包含的 GPA 患者的去识别初级保健数据进行了回顾性分析。进行潜在类别分析以根据代表各种器官受累的 16 类症状创建患者的症状群。在调整了年龄、性别、使用扩展的 Cox 比例风险模型在索引日期的 Townsend 剥夺五分之一和吸烟状况。在调整了季度使用类固醇作为时间依赖性协变量之后，使用复发事件模型比较了被认为是复发性细菌感染的间接指标的抗生素处方。在第一次访问、1 年和 3 年随访时比较了集群中常见合并症的累积频率。总共包括 649 名 GPA 患者 [中位年龄 60.0 (IQR: 49.6–70.1)]。确定了三个集群：主要伴有耳鼻喉科和咳嗽的疾病局限患者被分类为集群 1（n = 426）；第 2 组有全身性非肾脏疾病（n = 176）；而集群 3 中的患者患有以肾脏为主的疾病（n = 47）。集群 1 中的许多患者在 1 年末发展为全身性疾病。集群 2 和集群 3 的死亡率高于集群 1。集群 1 本身的死亡率比没有 GPA 的普通人群高 68%。在第 2 组和第 3 组中，抗生素处方的持续时间和并存疾病的频率也较高。在初级保健机构中，GPA 患者可分为三个不同的组，具有不同的预后、对复发性感染的易感性和合并症的存在。集群 1 演变成更普遍的疾病的趋势引发了对这些患者当前免疫抑制治疗方法的质疑。集群 1 本身的死亡率比没有 GPA 的普通人群高 68%。在第 2 组和第 3 组中，抗生素处方的持续时间和并存疾病的频率也较高。在初级保健机构中，GPA 患者可分为三个不同的组，具有不同的预后、对复发性感染的易感性和合并症的存在。集群 1 演变成更普遍的疾病的趋势引发了对这些患者当前免疫抑制治疗方法的质疑。集群 1 本身的死亡率比没有 GPA 的普通人群高 68%。在第 2 组和第 3 组中，抗生素处方的持续时间和并存疾病的频率也较高。在初级保健机构中，GPA 患者可分为三个不同的组，具有不同的预后、对复发性感染的易感性和合并症的存在。集群 1 演变成更普遍的疾病的趋势引发了对这些患者当前免疫抑制治疗方法的质疑。对反复感染的易感性和合并症的存在。集群 1 演变成更普遍的疾病的趋势引发了对这些患者当前免疫抑制治疗方法的质疑。对反复感染的易感性和合并症的存在。集群 1 演变成更普遍的疾病的趋势引发了对这些患者当前免疫抑制治疗方法的质疑。