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Ann Rheum Dis. 2019 Jan;78(1):122-130. doi: 10.1136/annrheumdis-2018-213708. Epub 2018 Nov 8.

Short-term progression of interstitial lung disease in systemic sclerosis predicts long-term survival in two independent clinical trial cohorts.

Collaborators (170)

Clements PJ, Tashkin DP, Elashoff R, Goldin J, Roth M, Furst D, Bulpitt K, Khanna D, Chung WL, Viasco S, Sterz M, Woolcock L, Yan X, Ho J, Vasunilashorn S, Costa ID, Seibold JR, Riley DJ, Amorosa JK, Hsu VM, McCloskey DA, Wilson JE, Varga J, Schraufnagel D, Wilbur A, Lopata M, Arami S, Cole-Saffold P, Simms R, Theodore A, Clarke P, Korn J, Tobin K, Nuite M, Silver R, Bolster M, Strange C, Schabel S, Smith E, Arnold J, Caldwell K, Bonner M, Wise R, Wigley F, White B, Hummers L, Bohlman M, Polito A, Leatherman G, Forbes E, Daniel M, Steen V, Read C, Cooper C, Wheaton S, Carey A, Ortiz A, Mayes M, Parsley E, Oldham S, Filemon T, Jordan S, Perry M, Connolly K, Golden J, Wolters P, Webb R, Davis J, Antolos C, Maynetto C, Fessler B, Olman M, Sanders C, Heck L, Parkhill T, Rothfield N, Metersky M, Cobb R, Aberles M, Ingenito F, Breen E, Mayes M, Mubarak K, Granda JL, Silva J, Injic Z, Alexander R, Furst D, Springmeyer S, Kirkland S, Molitor J, Hinke R, Mondt A, Thompson T, Rounds S, Weinstein M, Thompson B, Paulus H, Levy S, Martin D, Theodore AC, Simms RW, Kissin E, Cheong FY, Steen VD, Read CA Jr, Fridley C, Zulmatashvili M, Wise RA, Wigley FM, Hummers L, Leatherman G, Silver RM, Strange C, Hant FN, Ham J, Gibson K, Rosson D, Tashkin DP, Elashoff RM, Roth MD, Clements PJ, Furst D, Kafaja S, Kleerup E, Elashoff D, Goldin J, Ariola E, Marlis G, Mason-Berry J, Saffold P, Rodriguez M, Guzman L, Brook J, Golden J, Connolly MK, Eller A, Leong D, Lalosh M, Obata J, Varga J, Dematte J, Hinchcliff M, DeLuca C, Donnelly H, Marlin C, Riley DJ, Hsu VM, McCloskey DA, Phillips K, Khanna D, Martinez FJ, Schiopu E, Konkle J, Mayes M, Patel B, Assassi S, Tan F, Fischer A, Swigris J, Meehan R, Brown K, Warren T, Morrison M, Scholand MB, Frecht T, Carey P, Villegas M, Molitor J, Carlson P.

Author information

Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California, USA
Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California, USA.
Department of Biomathematics, University of California, Los Angeles, California, USA.
NIAID, NIH, Bethesda, Maryland, USA.
Rho Federal Systems, Inc., Chapel Hill, North Carolina, USA.
Department of Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Department of Medicine, Georgetown University, Washington, District of Columbia, USA.
Department of Medicine, University of Illinois Hospital, Chicago, Illinois, USA.
Department of Medicine, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
Department of Medicine, Duke University, Durham, North Carolina, USA.



To assess survival and identify predictors of survival in patients with systemic sclerosis-interstitial lung disease (SSc-ILD) who participated in the Scleroderma Lung Studies (SLS) I and II.


SLS I randomised 158 patients with SSc-ILD to 1  year of oral cyclophosphamide (CYC) vs placebo. SLS II randomised 142 patients to 1 year of oral CYC followed by 1 year of placebo vs 2 years of mycophenolate mofetil. Counting process Cox proportional hazard modelling identified variables associated with long-term mortality in SLS I and II. Internal validation was performed using joint modelling.


After a median follow-up of 8 years, 42% of SLS I patients died, and when known the cause of death was most often attributable to SSc. There was no significant difference in the time to death between treatment arms in SLS I or II. Higher baseline skin score, older age, and a decline in the forced vital capacity (FVC) and the diffusing capacity for carbon monoxide (DLCO) over 2 years were independently associated with an increased risk of mortality in SLS I. The Cox model identified the same mortality predictor variables using the SLS II data.


In addition to identifying traditional mortality risk factors in SSc (skin score, age), this study demonstrated that a decline in FVC and DLCO over 2 years was a better predictor of mortality than baseline FVC and DLCO. These findings suggest that short-term changes in surrogate measures of SSc-ILD progression may have important effects on long-term outcomes.


interstitial lung disease; survival; systemic sclerosis; treatment

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