4 Questions About Predictors in Systemic Sclerosis-Interstitial Lung Disease

Interstitial lung disease is the leading cause of mortality among patients with systemic sclerosis.

There are no validated prediction tools for rheumatologists to use to determine which patients’ lung disease will progress. Identifying risk factors for rheumatologists to use to predict progression is crucial.

Elizabeth Volkmann, MD, MS, who is an assistant professor of medicine in the Division of Rheumatology at David Geffen School of Medicine at UCLA, and founder and director of the Connective Tissue Disease-Interstitial Lung Disease Integrative Clinic Program at UCLA, is the lead author of a study that assessed survival and predictors of survival among patients with systemic sclerosis-interstitial lung disease (SSc-ILD) enrolled in the Scleroderma Lung Studies (SLS) I and II.

Rheumatology Consultant caught up with Dr Volkmann about her research.

Rheumatology Consultant: Can you tell us about the SLS I and SLS II clinical trials?

Elizabeth Volkmann: The SLS trials are two of the largest randomized controlled clinical trials ever published in systemic sclerosis. SLS I compared cyclophosphamide with placebo for patients with SSc-ILD and found that treatment with cyclophosphamide was associated with short-term improvement in lung function, breathlessness, and radiographic extent of pulmonary fibrosis. SLS II compared cyclophosphamide with mycophenolate for patients with SSc-ILD and found that both treatments were associated with similar improvements in lung function, breathlessness, and radiographic extent of pulmonary fibrosis. However, mycophenolate was safer and better tolerated compared with cyclophosphamide. There were more than twice as many deaths during the 2-year study period in SLS II in the cyclophosphamide group compared with the mycophenolate group.

RHEUM CON: Do patients with SSc-ILD typically have good prognosis and survival? How can a rheumatologist approach this?

EV: The prognosis for patients varies. Some patients experience rapid progression of their ILD despite treatment, which can lead to respiratory failure and death within 1 to 2 years. Other patients can experience improvement in their ILD with treatment. Currently, there is no validated prediction tool that rheumatologists can apply to determine which patients are likely to experience rapid progression of their lung disease. Our study is important because it identifies factors that rheumatologists can use to help predict which patients may experience rapid progression and may require a more aggressive treatment approach.

Identifying risk factors >>

RHEUM CON: Your study identified decline in forced vital capacity and diffusing capacity for carbon monoxide over 2 years as a predictor of survival. Historically, have risk factors and predictors of survival in this patient population been difficult to identify?

EV: Historical studies have identified predictors of survival. However, none of them have examined predictors of survival in the context of a clinical trial in which all patients have equal access to care, a standard treatment approach, and a uniform follow-up schedule. In addition, prior studies were observational, which means they assessed patients receiving various medications who did not have uniform follow-up or equal access to care. This makes it difficult to interpret the findings of these studies. The present study was the first to assess long-term survival in the 2 largest clinical trials for SSc-ILD. The findings suggest that a patient's initial response to therapy as defined by their course of forced vital capacity and diffusing capacity for carbon monoxide is an important indicator of their long-term survival even when you consider their age and baseline disease severity.

RHEUM CON: What are the clinical implications of your study and how can rheumatologists apply them to practice?

EV: Our study found that during the first 2 years of treatment with immunosuppression, the most important predictors of long-term mortality in SSc-ILD were increased age, increased extent of skin sclerosis, and a decline in lung function. Specifically, patients who had a significant decline in their lung function despite treatment had an increased risk of mortality, even after adjusting for their baseline disease severity. The results of this research may change how we manage patients with SSc-ILD in the future. Patients with SSc-ILD who experience an early decline in lung function and have an increased risk of death may benefit from receiving a more aggressive treatment approach that could include escalation of immunosuppression, addition of anti-fibrotic therapy, or evaluation for hematopoietic stem cell transplant. Systemic sclerosis providers should closely monitor lung function when ILD is present to accurately identify declines in lung function and promptly intervene to improve patient outcomes.

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Reference:

Volkmann ER, Tashkin DP, Sim M, et al. Short-term progression of interstitial lung disease in systemic sclerosis predicts long-term survival in two independent clinical trial cohorts. Ann Rheum Dis. 2019;78(1):122-130. doi:10.1136/annrheumdis-2018-213708.