Takayasu arteritis phenotypes and outcomes: A data-driven cluster analysis from a large international cohort

Takayasu arteritis is a large-vessel vasculitis with polymorphic clinical presentation and outcomes. In this large multi-ethnic Takayasu cohort, we aimed to determine how factors present at diagnosis cluster together and impact prognosis.

International multicentre retrospective cohort of consecutive patients with Takayasu arteritis fulfilling international criteria at tertiary referral centres. Clinical features, laboratory and radiological data at diagnosis were collected, as well as outcomes. A step-wise unsupervised approach was used for exploratory analyses, including principal component analysis (PCA) and hierarchical clustering on principal components. Survival curves were calculated using the Kaplan-Meier estimator.

852 patients were included (81.5% women; median age 30.6 years). After imputation of missing data, three clusters were unraveled with a progressively lower age at diagnosis from cluster 1 to 3, named 'supra-aortic', 'abdominal' and 'diffuse', respectively. 'Supra-aortic' cluster mainly presented with supra-aortic trunks' involvement (96.6%) and significantly higher rates of cerebrovascular events (16.7%). 'Abdominal' cluster presented a marked involvement of abdominal aorta (72.1%) and renal arteries (64.6%). 'Diffuse' cluster had widespread arterial involvement and significantly more extra-vascular symptoms. Elevated acute phase reactants were seen in 49.8%, 65.8% and 98.0% of patients within 'supra-aortic', 'abdominal' and 'diffuse' clusters, respectively. Compared to the 'supra-aortic' cluster, 'abdominal' patients had the highest risk of vascular complications (HR = 1.79, 95%CI 1.12-2.87), and 'diffuse' ones the greatest risk of future relapses (HR = 2.31, 95%CI 1.81-2.95).

The heterogeneous demographic, clinical, laboratory and radiological features at diagnosis split patients with Takayasu arteritis into three clusters, with prognostic implications over time.