Mycophenolate Mofetil Versus Placebo for Systemic Sclerosis-Related Interstitial Lung Disease: An Analysis of Scleroderma Lung Studies I and II

Abstract

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 (DLco), 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 DLco (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 DLco (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.

Conflict of interest statement

Competing interests: No non-financial conflicts of interest exist for any of the authors.

Financial conflicts of interest appear below:

ERV, PJC, RME, JG, GK, AMHV, and NL all report nothing to disclose.

DPT reports personal fees from EMD Serono, and non-financial support from Genentech, during the conduct of the study.

MDR reports non-financial support from Hoffmann-La Roche/Genentech, during the conduct of the study.

DEF reports Grant/Research support from AbbVie, Actelion, Amgen, BMS, Gilead, GSK, Novartis, Pfizer, Roche/Genentech, UCB, and consultant work with AbbVie, Amgen, BMS, Cytori, Janssen, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB Speaker’s Bureau (CME ONLY) AbbVie, Actelion, UCB during the course of the study.

DK reports personal fees from Bayer, grants from Bristol-Myer Squibb, personal fees from Cytori, personal fees from EMD Serono (Merck), personal fees from Forward, grants and personal fees from Genentech/Roche (InterMune), personal fees from Lycera during the course of the study.

© 2017, American College of Rheumatology.

Figures

Figure 1. Course of the FVC% from 3 to 24 Months in SLS II Patients Assigned to MMF versus SLS I Patients Assigned to Placebo Using Joint Model Analysis

The test of the overall treatment group effect is significant at P

Figure 2. Course of the DLCO% from 3 to 24 Months in SLS II Patients Assigned to MMF versus SLS I Patients Assigned to Placebo Using Joint Model Analysis

The test of the overall treatment group effect is significant at P

Figure 3. Course of the MRSS from 3 to 24 Months in SLS II Patients Assigned to MMF versus SLS I Patients Assigned to Placebo Using Joint Model Analysis

The test of the overall treatment group effect is significant at P

Figure 4. Course of the TDI from 3 to 24 Months in SLS II Patients Assigned to MMF versus SLS I Patients Assigned to Placebo Using Joint Model Analysis

The test of the overall treatment group effect is significant at P=0.0112. The dotted line represents the mean baseline value for the entire cohort.