Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: a European Scleroderma Trials and Research (EUSTAR) analysis

Abstract

ObjectivesMortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database.MethodsInclusion criteria were diagnosis of diffuse SSc and follow-up over 12±3 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression.ResultsOf 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model.ConclusionsThe use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trials.

Older age onset of systemic sclerosis – accelerated disease progression in all disease subsets

“…This is also in agreement with the relatively rare use of immunosuppressive drugs in patients with later disease onset; however, the fact that elderly patients are more vulnerable to risks of immunosuppressive therapies, especially to infections and malignancies, and that physicians might be more reluctant to prescribe immunosuppressive drugs in the elderly might also contribute to this observation. Our data support the suggestion of several other studies to use the older age at disease onset as an independent prognostic factor, together with the diffuse subset, lung involvement, PH and renal crisis [ 10 , 26 , 27 ] for a poor prognosis.…”

Correlation of retinal and choroidal microvascular impairment in systemic sclerosis

“…Severe complications of the kidneys, heart, lungs, and the gastrointestinal tract usually develop within 3 years of disease onset [32]. Several studies tried to identify predictive factors, such as patients' age, presence of digital ulcer, lung fibrosis, and CRP elevation, that are associated with a fast disease progression and lead to organ failure [33,34]. However, it is still challenging to predict disease progression in SSc patients.…”

Disease progression in systemic sclerosis

“…For both physicians and patients, SSc represents a major clinical challenge, as prediction of the disease course remains difficult. Disease progression has been shown to occur often [ 2 , 3 ]. However, many studies have been performed in selected subgroups of patients or have focused on specific organ domains.…”