Cyclophosphamide for Systemic Sclerosis-related Interstitial Lung Disease: A Comparison of Scleroderma Lung Study I and II

Elizabeth R Volkmann; Donald P Tashkin; Myung Sim; Ning Li; Dinesh Khanna; Michael D Roth; Philip J Clements; Anna-Maria Hoffmann-Vold; Daniel E Furst; Grace Kim; Jonathan Goldin; Robert M Elashoff

doi:10.3899/jrheum.180441

Cyclophosphamide for Systemic Sclerosis-related Interstitial Lung Disease: A Comparison of Scleroderma Lung Study I and II

J Rheumatol. 2019 Oct;46(10):1316-1325. doi: 10.3899/jrheum.180441. Epub 2019 Feb 15.

Authors

Elizabeth R Volkmann^{1

2}, Donald P Tashkin^{3

4}, Myung Sim^{3

4}, Ning Li^{3

4}, Dinesh Khanna^{3

4}, Michael D Roth^{3

4}, Philip J Clements^{3

4}, Anna-Maria Hoffmann-Vold^{3

4}, Daniel E Furst^{3

4}, Grace Kim^{3

4}, Jonathan Goldin^{3

4}, Robert M Elashoff^{3

4}

Affiliations

¹ From the Department of Medicine and Department of Radiology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California; Department of Biomathematics, University of California, Los Angeles, California; Department of Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA; Department of Rheumatology, Oslo University Hospital, Oslo, Norway. evolkmann@mednet.ucla.edu.
² E.R. Volkmann, MD, MS, Assistant Professor, Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine; D.P. Tashkin, MD, Emeritus Professor, Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine; M. Sim, PhD, Associate Professor, Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine; N. Li, PhD, Associate Professor, Department of Biomathematics, University of California, Los Angeles; D. Khanna, MD, MS, Department of Medicine, Professor, University of Michigan Medical School; M.D. Roth, MD, Professor, Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine; P.J. Clements, MD, MPH, Professor, Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine; A.M. Hoffmann-Vold, MD, PhD, Postdoctoral Candidate, Department of Rheumatology, Oslo University Hospital; D.E. Furst, MD, Emeritus Professor, Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine; G. Kim, PhD, Associate Professor, Department of Radiology, University of California, Los Angeles, David Geffen School of Medicine; J. Goldin, MD, PhD, Professor, Department of Radiology, University of California, Los Angeles, David Geffen School of Medicine; R.M. Elashoff, PhD, Distinguished Professor, Department of Biomathematics, University of California, Los Angeles. evolkmann@mednet.ucla.edu.
³ From the Department of Medicine and Department of Radiology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California; Department of Biomathematics, University of California, Los Angeles, California; Department of Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA; Department of Rheumatology, Oslo University Hospital, Oslo, Norway.
⁴ E.R. Volkmann, MD, MS, Assistant Professor, Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine; D.P. Tashkin, MD, Emeritus Professor, Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine; M. Sim, PhD, Associate Professor, Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine; N. Li, PhD, Associate Professor, Department of Biomathematics, University of California, Los Angeles; D. Khanna, MD, MS, Department of Medicine, Professor, University of Michigan Medical School; M.D. Roth, MD, Professor, Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine; P.J. Clements, MD, MPH, Professor, Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine; A.M. Hoffmann-Vold, MD, PhD, Postdoctoral Candidate, Department of Rheumatology, Oslo University Hospital; D.E. Furst, MD, Emeritus Professor, Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine; G. Kim, PhD, Associate Professor, Department of Radiology, University of California, Los Angeles, David Geffen School of Medicine; J. Goldin, MD, PhD, Professor, Department of Radiology, University of California, Los Angeles, David Geffen School of Medicine; R.M. Elashoff, PhD, Distinguished Professor, Department of Biomathematics, University of California, Los Angeles.

Abstract

Objective: To compare safety and efficacy outcomes between the cyclophosphamide (CYC) arms of Scleroderma Lung Study (SLS) I and II.

Methods: Participants enrolled in the CYC arms of SLS I (n = 79) and II (n = 69) were included. SLS I and II randomized participants to oral CYC for 1 year and followed patients for an additional year off therapy (in SLS II, patients received placebo in Year 2). Eligibility criteria for SLS I and II were nearly identical. Outcomes included the forced vital capacity (FVC%)-predicted and DLCO%-predicted (measured every 3 mos) and quantitative radiographic extent of interstitial lung disease (measured at 1 and 2 yrs for SLS I and SLS II, respectively). Joint models were created to evaluate the treatment effect on the course of the FVC/DLCO over 2 years while controlling for baseline disease severity.

Results: SLS I and II CYC participants had similar baseline characteristics. After adjusting for baseline disease severity, there was no difference in the course of the FVC%-predicted (p = 0.535) nor the DLCO%-predicted (p = 0.172) between the SLS I and II CYC arms. In both groups, treatment with CYC led to a significant improvement in the FVC%-predicted from 3 to 12 months, but no significant improvement beyond this point. Treatment with CYC had no effect on the DLCO for either group.

Conclusion: Treatment with 1 year of oral CYC led to similar improvements in lung function in both SLS I and II, although the effects were not sustained following cessation of CYC. These results suggest that increasing the duration of ILD therapy may improve outcomes for patients with systemic sclerosis-ILD.

Keywords: CYCLOPHOSPHAMIDE; INTERSTITIAL LUNG DISEASE; SYSTEMIC SCLEROSIS.

Publication types

Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Cohort Studies
Cyclophosphamide / adverse effects
Cyclophosphamide / therapeutic use*
Female
Follow-Up Studies
Humans
Immunosuppressive Agents / adverse effects
Immunosuppressive Agents / therapeutic use*
Lung / physiopathology
Lung Diseases, Interstitial / complications*
Lung Diseases, Interstitial / drug therapy*
Male
Middle Aged
Pulmonary Diffusing Capacity / drug effects
Scleroderma, Systemic / complications*
Scleroderma, Systemic / drug therapy*
Treatment Outcome
Vital Capacity / drug effects

Substances

Immunosuppressive Agents
Cyclophosphamide

Abstract

Publication types

MeSH terms

Substances

Grants and funding