Efficacy of Mycophenolate Mofetil and Oral Cyclophosphamide on Skin Thickness: Post Hoc Analyses From Two Randomized Placebo‐Controlled Trials

Objective To assess the efficacy of mycophenolate mofetil ( MMF ) and cyclophosphamide ( CYC ) on modified Rodnan skin score ( MRSS ) in participants enrolled in the Scleroderma Lung Study ( SLS ) I and II . Methods SLS I participants received daily oral CYC or matching placebo for 1 year, whereas SLS II participants received daily MMF for 2 years or daily oral CYC for 1 year followed by placebo for second year. We assessed the impact of MMF and CYC on the MRSS in SLS II over a 24‐month period. We also compared the change in MRSS in patients with diffuse cutaneous systemic sclerosis (dc SS c) assigned to CYC and MMF in SLS II and SLS I versus placebo in SLS I over a 24‐month period using a linear mixed model. Results In SLS II , the baseline mean ± SD MRSS was 14.0 ± 10.6 units for CYC and 15.3 ± 10.4 units for MMF ; 58.5% were classified as dc SS c. CYC and MMF were associated with statistically significant improvements in MRSS from baseline over the period of 24 months in dc SS c ( P < 0.05 at each time point), but there were no differences between the 2 groups. In the dc SS c subgroup, the change in MRSS from baseline to all 6‐month visits was similar in SLS II groups ( MMF , CYC , pooled cohort [ MMF + CYC ]) and in the SLS I CYC group and showed statistically significant improvements compared to SLS I placebo at 12, 18, and 24 months ( P < 0.05). Conclusion In SLS II , MMF and CYC treatment resulted in improvements in MRSS in patients with dc SS c over 24 months. In addition, MMF and CYC treatment resulted in statistically significant improvements in MRSS in patients with dc SS c when compared with the SLS I placebo group.