A recent study found that short-term progression rate of interstitial lung disease (ILD) in systemic sclerosis (SSc) is a better predictor of long-term survival than baseline ILD severity.
ILD progression was clinically detected over a two-year period as a gradual decline in two lung function parameters: forced vital capacity (FVC, the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible), and diffusing capacity for carbon monoxide (DLCO, the ability of the lungs to transfer oxygen from the air to blood).
The study, “Short-term Progression of Interstitial Lung Disease in Systemic Sclerosis Predicts Long-term Survival in Two Independent Clinical Trial Cohorts,” was published in Annals of the Rheumatic Diseases.
SSc is characterized by excessive scarring (fibrosis) in the skin and possibly in internal organs. When scarring occurs in the interstitial tissue between the lung alveoli and the bloodstream, it is referred to as SSc-ILD. ILD reduces the lungs’ capacity to expand and exchange gases, and is the leading cause of death among SSc patients, accounting for more than a third of SSc-related deaths.
Several factors are already known to be associated with an increased risk of mortality in SSc, including age, extent of cutaneous sclerosis, and ILD severity.
To better understand the survival rate among patients with SSc-ILD, and identify potential predictors of survival, researchers analyzed data from two clinical trials in this patient population — the Scleroderma Lung Study (SLS) I (NCT01762449; NCT00004563), and SLS II (NCT00883129). SLS I was conducted between 2000 and 2004; SLS II was conducted between 2009 and 2013.
SLS I involved 158 SSc-ILD patients (mean age 48.5 years), and investigated the effects of a one-year course of cyclophosphamide treatment versus placebo on lung function and health-related symptoms. SLS II compared the effects of one year of oral cyclophosphamide followed by 1 year of placebo versus two years of mycophenolate mofetil treatment in 142 SSc-ILD patients (mean age 52.3 years).
Cyclophosphamide and mycophenolate mofetil are two therapies used to suppress the immune system.
Results showed that during a median follow-up of eight years, 42% of SLS I patients and 21% of SLS II patients died. In these cases, when the cause of death was known, it was often because of SSc.
Results confirmed that some already-known risk factors, such as greater severity of skin involvement and older age, predicted worse long-term survival.
Importantly, the data also showed that short-term progression of ILD was a better predictor than baseline ILD severity of long-term survival. Specifically, patients who experienced a decline in lung function (FVC and DLCO parameters) over two years had a substantially increased risk of mortality.
Regarding treatment, researchers found that cyclophosphamide did not improve long-term survival compared with placebo in SLS I. Similarly, no significant differences were found in SLS II patients between those taking cyclophosphamide followed by a year of placebo versus two years of mycophenolate mofetil treatment.
Based on these results, the team suggests that “short-term treatment with cyclophosphamide and mycophenolate mofetil may not improve long-term outcomes of patients with SSc-ILD.”
Importantly, the team concluded that although “low baseline FVC was associated with an increased risk of mortality, the course of FVC and DLCO over 24 months appeared to be more robust predictors of long-term survival … than baseline measurements of these parameters.”
The researchers stated that preventing ILD progression may have an important impact on SSc-ILD patients’ long-term outcomes. They suggest that SSc-ILD patients with an early decline in lung function “may benefit from receiving a more aggressive treatment approach that could include escalation of immunosuppression, addition of antifibrotic therapy and/or evaluation for hematopoietic stem cell transplant.”