title: Prediction of improvement in skin fibrosis in diffuse cutaneous systemic sclerosis: a EUSTAR analysis.
abstract: Improvement of skin fibrosis is part of the natural course of diffuse cutaneous systemic sclerosis (dcSSc). Recognising those patients most likely to improve could help tailoring clinical management and cohort enrichment for clinical trials. In this study, we aimed to identify predictors for improvement of skin fibrosis in patients with dcSSc.
  
  
  
  We performed a longitudinal analysis of the European Scleroderma Trials And Research (EUSTAR) registry including patients with dcSSc, fulfilling American College of Rheumatology criteria, baseline modified Rodnan skin score (mRSS) ≥7 and follow-up mRSS at 12±2 months. The primary outcome was skin improvement (decrease in mRSS of >5 points and ≥25%) at 1 year follow-up. A respective increase in mRSS was considered progression. Candidate predictors for skin improvement were selected by expert opinion and logistic regression with bootstrap validation was applied.
  
  
  
  From the 919 patients included, 218 (24%) improved and 95 (10%) progressed. Eleven candidate predictors for skin improvement were analysed. The final model identified high baseline mRSS and absence of tendon friction rubs as independent predictors of skin improvement. The baseline mRSS was the strongest predictor of skin improvement, independent of disease duration. An upper threshold between 18 and 25 performed best in enriching for progressors over regressors.
  
  
  
  Patients with advanced skin fibrosis at baseline and absence of tendon friction rubs are more likely to regress in the next year than patients with milder skin fibrosis. These evidence-based data can be implemented in clinical trial design to minimise the inclusion of patients who would regress under standard of care.
authors.affiliation: Division of Rheumatology, University Hospital Zurich, Zurich, Switzerland Department of Internal Medicine and Rheumatology, Cantacuzino Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Rucsandra
authors.initials: R
authors.lastname: Dobrota
authors.affiliation: Division of Rheumatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Britta
authors.initials: B
authors.lastname: Maurer
authors.affiliation: Graf biostatistics, Winterthur, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Graf
authors.affiliation: Division of Rheumatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Suzana
authors.initials: S
authors.lastname: Jordan
authors.affiliation: Department of Internal Medicine and Rheumatology, Cantacuzino Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
authors.forename: Carina
authors.initials: C
authors.lastname: Mihai
authors.affiliation: Department of Rheumatology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Otylia
authors.initials: O
authors.lastname: Kowal-Bielecka
authors.affiliation: Department of Rheumatology, University Paris Descartes and Cochin Hospital, Paris, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Allanore
authors.affiliation: Division of Rheumatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Distler
mesh_terms: D000328:Adult; D018450:Disease Progression; D005260:Female; D005355:Fibrosis; D005500:Follow-Up Studies; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012042:Registries; D045743:Scleroderma, Diffuse / Q000473:pathology* / Q000503:physiopathology; D012720:Severity of Illness Index; D012867:Skin / Q000473:pathology*; D012882:Skin Tests / Q000379:methods; D013710:Tendons / Q000503:physiopathology
keywords: Epidemiology; Outcomes research; Systemic Sclerosis