Prediction of worsening of skin fibrosis in patients with diffuse cutaneous systemic sclerosis using the EUSTAR database

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • EUSTAR co-authors - (Author)
  • Department of internal Medicine 3
  • Department of Dermatology
  • University of Zurich
  • Graf Biostatistics
  • Justus Liebig University Giessen
  • University of Pecs
  • University College London
  • University of Basel
  • Bayer AG
  • University of Michigan, Ann Arbor
  • University of Florence
  • University of Bari
  • Charles University Prague
  • Medical University of Białystok
  • University of Genoa
  • Universita' di Napoli Federico II
  • Charité – Universitätsmedizin Berlin
  • Iuliu Hatieganu University of Medicine and Pharmacy
  • Université Paris Cité
  • National and Kapodistrian University of Athens
  • IRCCS Fondazione Policlinico San Matteo - Pavia
  • Complutense University
  • University Hospital Centre Rijeka
  • Geneva University Hospitals
  • Medical University of Silesia in Katowice
  • University of Padua
  • University of Ljubljana
  • Stella Maris
  • Marche Polytechnic University
  • Assistance publique – Hôpitaux de Paris
  • Department of Internal Medicine 3
  • TUD Dresden University of Technology

Abstract

Objectives 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.

Details

Original languageEnglish
Pages (from-to)1124-1131
Number of pages8
JournalAnnals of the rheumatic diseases
Volume74
Issue number6
Publication statusPublished - 8 May 2015
Peer-reviewedYes

External IDs

PubMed 24981642
ORCID /0000-0002-4330-1861/work/151982017