University of California, Los Angeles.
University of Michigan Medical School, Ann Arbor.
Arthritis Rheumatol. 2017 Jul;69(7):1451-1460. doi: 10.1002/art.40114. Epub 2017 May 23.
To compare mycophenolate mofetil (MMF) with placebo for the treatment of systemic sclerosis (SSc)-related interstitial lung disease (ILD).
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.
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.
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.
比较霉酚酸酯（MMF）与安慰剂治疗系统性硬化症（SSc）相关间质性肺病（ILD）。
我们纳入了 Scleroderma Lung Study（SLS）I 安慰剂组和 SLS II MMF 组的参与者。SLS I 将参与者随机分配接受口服环磷酰胺（CYC）或安慰剂治疗 1 年，而 SLS II 将参与者随机分配接受 MMF 治疗 2 年或 CYC 治疗 1 年，然后接受安慰剂治疗 1 年。SLS I 和 SLS II 的入组标准几乎相同。主要结局为预测用力肺活量（FVC）的百分比，关键次要结局包括预测一氧化碳弥散量（DLco）的百分比、改良 Rodnan 皮肤厚度评分（MRSS）和呼吸困难。创建联合模型以评估 2 年内这些结局的治疗效果。
在基线时，SLS II 中 MMF 治疗组（n=69）和 SLS I 中安慰剂治疗组（n=79）的男女比例和疾病持续时间、SSc 亚型、皮肤疾病范围和预测 FVC 的百分比相似。SLS II 中接受 MMF 治疗的患者年龄稍大（平均±标准差年龄 52.6±9.7 岁与 48.1±12.4 岁；P=0.0152），预测 DLco 的百分比较高（平均±标准差 54.0±11.1 与 46.2±13.3；P=0.0002）。与 SLS I 中的安慰剂治疗组相比，在调整基线疾病严重程度后，与安慰剂相比，MMF 治疗与预测 FVC（P<0.0001）、预测 DLco（P<0.0001）、MRSS（P<0.0001）和呼吸困难（P=0.0112）的改善相关。
尽管比较来自不同试验的参与者存在固有局限性，但与安慰剂相比，即使在考虑到基线疾病严重程度后，MMF 治疗也与生理结局和呼吸困难的改善相关。这些结果进一步证实了 MMF 治疗 SSc 相关 ILD 的用途。
