Analysis of the European Scleroderma Trials and Research (EUSTAR) registry revealed that higher baseline modified Rodnan skin score (mRSS) and absence of tendon friction rub are predictors of skin fibrosis regression in a cohort of patients with diffuse cutaneous systemic sclerosis (dcSSc).

“There is a window of opportunity in [patients with] diffuse SSc to prevent damage on skin. This window of opportunity in high-risk patients is reflected by lower mRSS values, which have a higher probability to progress, while patients with already advanced mRSS values are more likely to regress under standard of care. Thus, much focus should be put on identifying [those with] diffuse SSc as early as possible during their disease course for potential therapeutic interventions,” noted the corresponding author Dr. Oliver Distler in an interview with Rheumatology Advisor.

Regression of skin fibrosis is a feature of the natural history of dcSSc. However, the pattern of regression can be quite heterogeneous despite improvements in predicting progression. 


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Further, it is unclear to what extent patients who may have regression of dcSSc would benefit from treatment beyond standard care. Identification of these patients is also important for research purposes to ensure that regression is not attributed to a treatment effect.

Rucsandra Dobrota, MD, of the Division of Rheumatology at University Hospital Zurich in Switzerland and colleagues conducted a longitudinal analysis of data from the EUSTAR patient registry. The registry included patients who met the American College of Rheumatology criteria with dcSSc and mRSS of ≥ 7. The participants were followed up approximately 12 months later to assess for skin improvement.

A total of 919 participants with dcSSc were included in the study, and 24% (N = 218) demonstrated improvement in skin scores at 1-year follow-up. The average age of the participants was 51 years and 78.3% were female, with a mean disease duration of 42.5 months and mRSS of 16.

After multivariable analysis, it was found that high baseline mRSS was the best predictor of skin improvement during follow-up (P < .001). For instance, a baseline mRSS of 22 points versus 14 points was associated with a 2-fold risk for skin regression (odds ratio 2.316) over a 1-year period. Other potential predictors of regression included absence of tendon friction rubs and absence of anti-Scl-70 antibodies.

In contrast, 10% of the participants (N = 95) demonstrated progression during follow-up. These patients tended to have a lower baseline mRSS (P < .001).

For clinical research design purposes, a baseline mRSS of 18 to 25 performs well as a cutoff to identify participants more likely to progress versus regress. 

Summary and Clinical Applicability

This longitudinal analysis of the EUSTAR registry found that those with dcSSc who had baseline advanced skin fibrosis and absence of tendon friction rub were more likely to have regression of skin fibrosis. These patients were also more likely to have higher baseline mRSS, absence of friction rub, and anti-Scl70 negativity.

Dr. Distler continued, “This study complements a recent study from our group, [which] should be interpreted together with this study. It is also important to note that this study does not mean that patients with advanced skin fibrosis should not be treated, but they might need different treatment strategies and their disease course should be interpreted considering that regression under standard of care is not unlikely.”

These results should have an impact on the development of clinical trials to exclude those at higher likelihood for regression with standard care. 

Limitations and Disclosures

Limitations of the study included missing data from the registry,and a potentially arbitrary inclusion threshold of mRSS > 7. In addition, the final prediction model would only explain approximately 16% of skin fibrosis regression.  

Reference

Dobrota R, Maurer B, Graf N, et al. Prediction of improvement in skin fibrosis in diffuse cutaneous systemic sclerosis: a EUSTAR analysis. Ann Rheum Dis. 2016 Mar 25. [Epub ahead of print]