Progressive skin fibrosis tied to poor lung function, survival in systemic sclerosis
Progression of skin fibrosis* within 1 year is associated with long-term deterioration in lung function and worse survival in individuals with diffuse cutaneous systemic sclerosis (dcSSc), according to data from the EUSTAR** cohort.
The visceral complications of this rare SSc subtype is associated with poor outcomes, with pulmonary complications being the leading cause of mortality. [Best Pract Res Clin Rheumatol 2010;24:387-400; Ann Rheum Dis 1999;58:635-640] “[Our findings suggest that] patients with short-term progressive skin disease should be carefully monitored for organ progression in the following years,” said the researchers, after evaluating 1,021 participants.
As identifying at-risk patients prior to the development of irreversible visceral complications is a major challenge, the researchers said, “[Our findings may] help clinicians to identify patients at risk of [visceral organ] progression in clinical practice [for early treatment intervention].”
After a median follow-up of 3.4 years, significantly more participants with skin fibrosis progression within a year (skin progressors, 7.6 percent) had a ≥10 percent FVC*** decline (53.6 percent vs 34.4 percent; p<0.001) and all-cause death (15.4 percent vs 7.3 percent; p=0.003) than those without skin fibrosis (non-progressors). [Ann Rheum Dis 2019;78:648-656]
Multivariate analysis revealed an independent association between skin fibrosis progression and FVC decline (hazard ratio [HR], 1.79, 95 percent confidence interval [CI], 1.20–2.65; p=0.004) and all-cause death (HR, 2.58, 95 percent CI, 1.31–5.09; p=0.006).
Moreover, exploratory analysis showed a higher likelihood of FVC-DLCO# decline among skin progressors vs non-progressors (56.4 percent vs 39.8 percent; p=0.004).
In particular, patients whose skin fibrosis had progressed within 15 months of dcSSc diagnosis had a poorer course of disease and worse survival than non-progressors, as indicated by the higher rates of FVC decline (58.3 percent vs 29.2 percent; p=0.019) and all-cause death (21.1 percent vs 2.8 percent; p=0.009) among progressors.
However, considering the mean disease duration (>7 years), it appears that most cases were not early disease, the researchers pointed out. “This underlines the heterogeneity of the disease course … Therefore, clinicians should pay attention to all patients with progression of skin fibrosis, even those with longer disease duration.”
Among patients with a low baseline mRSS## (≤22/51 units), skin progressors similarly had a higher probability of FVC decline (57.4 percent vs 33.9 percent; p<0.001) and all-cause death (13.4 percent vs 7.2 percent; p=0.017) compared with non-progressors.
Evaluating these subgroups may optimize cohort enrichment for further studies, which according to the researchers, “leads to populations with more severe disease at higher risk of organ progression and overall death.”
mRSS: A surrogate marker
The progression of mRSS within a year is an excellent surrogate marker for new onset or deterioration of visceral organ involvement and mortality in SSc, thus supporting the use of mRSS as a clinical endpoint in this setting, said the researchers. “As a surrogate marker in SSc … [mRSS] will be helpful for cohort enrichment in future trials and risk stratification in clinical practice.”
Researchers called for further investigation to verify the potential of mRSS as an appropriate surrogate marker and to support similar findings from older studies. [Arthritis Rheum 2001;44:2828-2835; Arthritis Rheum 2000;43:2445-2454]