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Mycophenolate Mofetil Versus Placebo for Systemic Sclerosis–Related Interstitial Lung Disease: An Analysis of Scleroderma Lung Studies I and II
Author(s) -
Volkmann Elizabeth R.,
Tashkin Donald P.,
Li Ning,
Roth Michael D.,
Khanna Dinesh,
HoffmannVold AnnaMaria,
Kim Grace,
Goldin Jonathan,
Clements Philip J.,
Furst Daniel E.,
Elashoff Robert M.
Publication year - 2017
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40114
Subject(s) - dlco , placebo , medicine , interstitial lung disease , scleroderma (fungus) , diffusing capacity , vital capacity , mycophenolic acid , gastroenterology , spirometry , lung , surgery , transplantation , pathology , lung function , asthma , inoculation , alternative medicine
Objective To compare mycophenolate mofetil (MMF) with placebo for the treatment of systemic sclerosis (SSc)–related interstitial lung disease (ILD). Methods We included participants enrolled in the placebo arm of Scleroderma Lung Study (SLS) I and the MMF arm of SLS II. SLS I randomized participants to receive either oral cyclophosphamide (CYC) or placebo for 1 year, while SLS II randomized participants to receive either MMF for 2 years or oral CYC for 1 year followed by 1 year of placebo. Eligibility criteria for SLS I and SLS II were nearly identical. The primary outcome was % predicted forced vital capacity (FVC), and key secondary outcomes included % predicted diffusing capacity for carbon monoxide (DL co ), the modified Rodnan skin thickness score (MRSS), and dyspnea. Joint models were created to evaluate the treatment effect on the course of these outcomes over 2 years. Results At baseline, the MMF‐treated group in SLS II (n = 69) and the placebo‐treated group in SLS I (n = 79) had similar percentages of men and women and similar disease duration, SSc subtype, extent of skin disease, and % predicted FVC. MMF‐treated patients in SLS II were slightly older (mean ± SD age 52.6 ± 9.7 years versus 48.1 ± 12.4 years; P = 0.0152) and had higher % predicted DL co (mean ± SD 54.0 ± 11.1 versus 46.2 ± 13.3; P = 0.0002) than placebo‐treated patients in SLS I. After adjustment for baseline disease severity, treatment with MMF in comparison with placebo was associated with improved % predicted FVC ( P < 0.0001), % predicted DL co ( P < 0.0001), MRSS ( P < 0.0001), and dyspnea ( P = 0.0112) over 2 years. Conclusion Although there are inherent limitations in comparing participants from different trials, treatment with MMF was associated with improvements in physiologic outcomes and dyspnea compared with placebo, even after accounting for baseline disease severity. These results further substantiate the use of MMF for the treatment of SSc‐related ILD.