Cluster analysis of patients with granulomatosis with polyangiitis (GPA) based on clinical presentation symptoms: a UK population-based cohort study

Rasiah Thayakaran, Ruchika Goel, Nicola J Adderley, Joht Singh Chandan, Dawit Zemedikun, Krishnarajah Nirantharakumar, Lorraine Harper

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

Original languageEnglish
Article number201
JournalArthritis Research & Therapy
Volume24
Issue number1
DOIs
Publication statusPublished - Dec 2022
Externally publishedYes

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