Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study

Ann Rheum Dis. 2018 Apr;77(4):563-570. doi: 10.1136/annrheumdis-2017-211912. Epub 2018 Jan 6.

Abstract

Objectives: Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs).

Methods: The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV).

Results: 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%.

Conclusions: Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years.

Trial registration number: NCT02339441.

Keywords: autoantibodies; outcomes research; systemic sclerosis.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Area Under Curve
  • Disease Progression
  • Early Diagnosis
  • Female
  • Humans
  • Logistic Models
  • Male
  • Predictive Value of Tests
  • Prospective Studies
  • RNA Polymerase III / analysis
  • ROC Curve
  • Scleroderma, Diffuse / diagnosis*
  • Scleroderma, Diffuse / enzymology
  • Scleroderma, Diffuse / pathology
  • Severity of Illness Index*
  • Skin / pathology
  • Skin Tests / statistics & numerical data*

Substances

  • RNA Polymerase III

Associated data

  • ClinicalTrials.gov/NCT02339441