title: Prediction of worsening of skin fibrosis in patients with diffuse cutaneous systemic sclerosis using the EUSTAR database.
abstract: OBJECTIVE
  To identify predictive parameters for the progression of skin fibrosis within 1 year in patients with diffuse cutaneous SSc (dcSSc).
  
  
  METHODS
  An observational study using the EUSTAR database was performed. Inclusion criteria were dcSSc, American College of Rheumatology (ACR) criteria fulfilled, modified Rodnan skin score (MRSS) ≥7 at baseline visit, valid data for MRSS at 2nd visit, and available follow-up of 12±2 months. Worsening of skin fibrosis was defined as increase in MRSS >5 points and ≥25% from baseline to 2nd visit. In the univariate analysis, patients with progressive fibrosis were compared with non-progressors, and predictive markers with p<0.2 were included in the logistic regression analysis. The prediction models were then validated in a second cohort.
  
  
  RESULTS
  A total of 637 dcSSc patients were eligible. Univariate analyses identified joint synovitis, short disease duration (≤15 months), short disease duration in females/patients without creatine kinase (CK) elevation, low baseline MRSS (≤22/51), and absence of oesophageal symptoms as potential predictors for progressive skin fibrosis. In the multivariate analysis, by employing combinations of the predictors, 17 models with varying prediction success were generated, allowing cohort enrichment from 9.7% progressive patients in the whole cohort to 44.4% in the optimised enrichment cohort. Using a second validation cohort of 188 dcSSc patients, short disease duration, low baseline MRSS and joint synovitis were confirmed as independent predictors of progressive skin fibrosis within 1 year resulting in a 4.5-fold increased prediction success rate.
  
  
  CONCLUSIONS
  Our study provides novel, evidence-based criteria for the enrichment of dcSSc cohorts with patients who experience worsening of skin fibrosis which allows improved clinical trial design.
authors: Division of Rheumatology, University Hospital Zurich, Zurich, Switzerland.
authors: Britta
authors: B
authors: Maurer
authors: Graf Biostatistics, Winterthur, Switzerland.
authors: Nicole
authors: N
authors: Graf
authors: Division of Rheumatology, University Hospital Zurich, Zurich, Switzerland.
authors: Beat A
authors: BA
authors: Michel
authors: Department of Rheumatology and Clinical Immunology, Justus-Liebig University Giessen, Kerckhoff-Klinik, Bad Nauheim, Germany.
authors: Ulf
authors: U
authors: Müller-Ladner
authors: Department of Rheumatology and Immunology, Faculty of Medicine, University of Pécs, Pécs, Hungary.
authors: László
authors: L
authors: Czirják
authors: Centre for Rheumatology, Royal Free and University College London Medical School, London, UK.
authors: Christopher P
authors: CP
authors: Denton
authors: Department of Rheumatology, University Hospital Basel, Basel, Switzerland.
authors: Alan
authors: A
authors: Tyndall
authors: Bayer Pharma AG, Berlin, Germany.
authors: Carola
authors: C
authors: Metzig
authors: Bayer Pharma AG, Berlin, Germany.
authors: Vivian
authors: V
authors: Lanius
authors: University of Michigan Scleroderma Program, Ann Arbor, Michigan, USA.
authors: Dinesh
authors: D
authors: Khanna
authors: Division of Rheumatology, University Hospital Zurich, Zurich, Switzerland.
authors: Oliver
authors: O
authors: Distler
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003402:Creatine Kinase / Q000097:blood; D016208:Databases, Factual; D003661:Decision Support Techniques; D003680:Deglutition Disorders / Q000209:etiology; D018450:Disease Progression; D004417:Dyspnea / Q000209:etiology; D005260:Female; D005355:Fibrosis; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D045743:Scleroderma, Diffuse / Q000097:blood / Q000150:complications / Q000473:pathology*; D012720:Severity of Illness Index; D012737:Sex Factors; D012867:Skin / Q000473:pathology*; D013585:Synovitis / Q000209:etiology; D013997:Time Factors
chemical_list: D003402:Creatine Kinase
keywords: Outcomes Research; Qualitative Research; Systemic Sclerosis