Older age, active digital ulcers, lung tissue scarring, muscle weakness, and increased levels of C-reactive protein (CRP) are predictive factors of progressive organ damage in people with systemic sclerosis (SSc), a study has found.
Taking these factors into consideration may help clinicians to identify patients at risk of SSc worsening, and to implement preventive measures.
These findings were reported in a study, “Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: a European Scleroderma Trials and Research (EUSTAR) analysis,” that was published in the journal Annals of the Rheumatic Diseases.
SSc, also known as scleroderma, is a disease characterized by diffuse fibrosis (scarring) and abnormalities of the joints, skin, and internal organs. It is associated with a relatively high mortality rate for a rheumatic disease, and death usually results from organ failure — primarily lung disease.
Thickening of the skin, which is easy to measure and associated with the organ failure risk in SSc, is often used as an endpoint for clinical trials of the disease. However, as this is an indirect measurement of organ health, more concrete clinical endpoints are still needed to accurately determine the efficacy of a treatment in a way that complies with the requirements of regulatory agencies.
This highlights the need for new strategies to define populations of patients who are at higher risk for progressive organ damage, and to improve the outcomes of clinical trials testing targeted therapies on these patients.
An international research team reviewed clinical information from the EUSTAR database, which includes data for approximately 15,000 people with SSc, to identify useful predictive factors for organ failure in SSc.
The researchers focused on data collected from 706 people who underwent a first evaluation in 2009 or later, and who also had either a follow-up appointment or died nine to 15 months later.
Based on measures of organ function, including aspects of kidney, lung, and heart health, patients were defined as either having or not having worsening disease. The researchers then conducted a series of statistical models to see what factors evaluated in the initial visit were predictive of worse outcomes a year later.
They found that older age, active digital ulcers (small sores that form on the fingers and toes as a result of a lack of blood flow), lung fibrosis, muscle weakness, and high CRP levels were all associated with an increased risk of organ failure.
“We showed that the probability of a 60-year-old patient with lung fibrosis, digital ulcers, muscle weakness, and CRP elevation developing disease worsening within the observation period increases to 74.5% compared with 32.2% for the whole study population,” the researchers reported.
They also noted that these characteristics are directly tied to many of the disease-associated mechanisms, such as CRP (a marker of systemic inflammation).
The team believes that this information may be applied for the design of more efficient and informative clinical trials in the future.
“This study provides evidence-based information from the largest SSc database available worldwide regarding which patients are appropriate for inclusion in these clinical trials,” they wrote.