Novel score predicts mortality risk in systemic sclerosis

medwireNews: Early mortality in patients with systemic sclerosis who are eligible for intensive therapies can be predicted with the novel Risk score for Early mortality to Stratify for Intensive SSc Therapy, say researchers.

“Unlike more complex tools, RESIST offers a simplified and pragmatic approach that is readily applicable in everyday practice,” write Ann-Christin Pecher (University Hospital Tübingen, Germany) and colleagues in the Annals of Rheumatic Diseases.

“Its ability to stratify patients into clinically meaningful risk categories highlights its potential to inform therapeutic decision-making.”

The researchers explain that “[c]ellular therapies, such as haematopoietic stem cell transplantation, chimeric antigen receptor T-cell therapy, and T-cell engager, are emerging options for severe or refractory SSc but carry significant risks, necessitating precise patient selection.”

To determine the variables for inclusion in the RESIST score, the researchers examined data from the EUSTAR cohort on 4526 patients from more than 180 international centers who had a definitive diagnosis of SSc and at least one follow-up visit since 2010. The patients were 65 years or younger (mean 48.8 years), did not have a history of renal crisis, had a left ventricular ejection fraction (LVEF) above 40%, a diffusing capacity of the lung for carbon monoxide (DLCO) above 40%, a forced vital capacity above 45%, and no contraindications for cellular therapies.

The majority of participants were women (84.2%) and White (92.7%), with an average time since their first non-Raynaud’s disease diagnosis of 6.6 years. The most common form of SSc was limited cutaneous (51.0%), while 36.2% had diffuse cutaneous SSC, and 12.9% had no skin involvement.

The duration of follow-up was 53 months, and 138 individuals died within 5 years.

The researchers found that patients who died were more likely than those who survived to be men (28.3 vs 15.4%), older (52.5 vs 48.6 years), over 55 years-of-age (45.7 vs 31.7%), underweight (BMI <20 kg/m²; 19.6 vs 13.4%), and to have diffuse cutaneous SSc (61.3 vs 35.3%).

Cox regression analysis revealed numerous factors significantly associated with an increased mortality risk, eight of which were included in the final RESIST model based also on clinical expertise and the medical literature. These were male sex; diffuse cutaneous SSc; age above 55 years; C-reactive protein level above the upper limit of normal; current or previous digital ulcer; modified Rodnan skin score above 14 points; LVEF below 60%; and DLCO below 60%.

The model was found to have “good discrimination,” the team notes, selecting patients at increased risk for mortality with a corrected C-index of 0.78, and an area under the receiver operating characteristic curve (AUC) of 79% at both 3 and 5 years.

Patients with a score of 0 points were classified as at low mortality risk, while a score of 1–22 points was deemed intermediate risk, and above 22 points high risk. Low-risk patients had a 5-year survival of 99% versus 96% in the intermediate-risk group, and 82% in high-risk patients.

The researchers then performed pseudo external validation of the score using data on 6251 patients initially excluded from the development cohort due to missing information on the inclusion criteria. RESIST’s good discrimination of mortality risk was maintained, with a C-index of 0.75 and an AUC of 75% at 3 years and 78% at 5 years. Five-year survival was 99% in low-risk patients, 95% in the intermediate-risk group, and 81.0% in high-risk patients.

Pecher et al recommend that a score above 22 points “should not be interpreted as a prerequisite for cellular therapy; however, patients with high scores should be evaluated at specialised centres to explore appropriate therapeutic options.”

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Ann Rheum Dis 2026; doi:10.1016/j.ard.2026.01.016