Novel clustering approach to understanding distinct phenotypes of patients with systemic sclerosis

Despite earlier clustering studies on systemic sclerosis (SSc), how clinical subgroups differ in disease burden, treatment and patient-physician dynamics remains unclear. This study applied a novel clustering method to identify clinical subgroups.

Data were analysed from 1906 adults with SSc and their treating rheumatologists across the USA, France, Germany, Italy, Spain, UK and Japan (March-September 2022).

Data were collected by Adelphi Real World as part of an independent survey titled the SSc I Disease Specific Programme, comprising data from the USA, France, Germany, Italy, Spain, UK and Japan.

Physicians completed case record forms; patients completed self-reported questionnaires. Latent class clustering was conducted using five physician-reported variables: affected body areas, symptoms, severity, flares in the past 12 months and remission status.

This was a non-interventional, observational, retrospective study.

A cluster solution was selected based on model fit and clinical interpretability. We compared time to diagnosis, symptoms at diagnosis, postdiagnosis trajectories, physician management and patient treatment perspectives across clusters.

We identified four clusters representing a gradient of disease severity, with all clusters comprising >75% females. Clusters 1/2 comprised younger patients with fewer concomitant conditions; Clusters 3/4 showed greater internal organ involvement and disease severity. Raynaud's phenomenon (RP) was the most frequent first symptom (physician-reported: 73%-85%; patient-reported: 63%-79%), but those with first symptoms other than RP were diagnosed faster (mean 1.06 vs 1.62 years). Musculoskeletal involvement was most pronounced in Clusters 2/4. Postdiagnosis (3.7-7.2 years), the number of symptoms and affected body areas decreased in Cluster 1, increased in Cluster 4 and remained relatively stable in Clusters 2/3. Improvement in disease progression within the first 2 years postdiagnosis was more often reported in Clusters 1/2 vs 3/4 (33%-34% vs 8%-20%). Most patients across clusters reported that the main benefit they wanted from treatment was to get rid of the disease.

This analysis improves understanding of SSc beyond limited/diffuse subtypes. Musculoskeletal involvement emerged as a contributor to SSc burden, supporting its integration into monitoring/stratification strategies for earlier identification of high-risk patients.