Divison of Rheumatology, University Hospital Zurich, Zurich, Switzerland.
Department of Internal Medicine, University of Erlangen-Nuremberg, Erlangen, Germany.
Ann Rheum Dis. 2015 Jun;74(6):1188-94. doi: 10.1136/annrheumdis-2013-204522. Epub 2014 Jan 17.
To assess the effects of Rituximab (RTX) on skin and lung fibrosis in patients with systemic sclerosis (SSc) belonging to the European Scleroderma Trial and Research (EUSTAR) cohort and using a nested case-control design.
Inclusion criteria were fulfilment of American College of Rheumatology classification criteria for SSc, treatment with RTX and availability of follow-up data. RTX-treated patients were matched with control patients from the EUSTAR database not treated with RTX. Matching parameters for skin/lung fibrosis were the modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), follow-up duration, scleroderma subtype, disease duration and immunosuppressive co-treatment. The primary analysis was mRSS change from baseline to follow-up in the RTX group compared with the control group. Secondary analyses included change of FVC and safety measures.
63 patients treated with RTX were included in the analysis. The case-control analysis in patients with severe diffuse SSc showed that mRSS changes were larger in the RTX group versus matched controls (N=25; -24.0±5.2% vs -7.7±4.3%; p=0.03). Moreover, in RTX-treated patients, the mean mRSS was significantly reduced at follow-up compared with baseline (26.6±1.4 vs 20.3±1.8; p=0.0001). In addition, in patients with interstitial lung disease, RTX prevented significantly the further decline of FVC compared with matched controls (N=9; 0.4±4.4% vs -7.7±3.6%; p=0.02). Safety measures showed a good profile consistent with previous studies in autoimmune rheumatic diseases.
The comparison of RTX treated versus untreated matched-control SSc patients from the EUSTAR cohort demonstrated improvement of skin fibrosis and prevention of worsening lung fibrosis, supporting the therapeutic concept of B cell inhibition in SSc.
评估利妥昔单抗（RTX）对欧洲硬皮病试验和研究（EUSTAR）队列中系统性硬化症（SSc）患者皮肤和肺纤维化的影响，并采用巢式病例对照设计。
纳入标准为符合美国风湿病学会 SSc 分类标准、接受 RTX 治疗以及具有随访数据。将接受 RTX 治疗的患者与 EUSTAR 数据库中未接受 RTX 治疗的对照患者相匹配。皮肤/肺纤维化的匹配参数为改良罗德曼皮肤评分（mRSS）、用力肺活量（FVC）、随访时间、硬皮病亚型、疾病持续时间和免疫抑制联合治疗。主要分析是 RTX 组与对照组从基线到随访的 mRSS 变化。次要分析包括 FVC 变化和安全性措施。
共纳入 63 例接受 RTX 治疗的患者进行分析。在严重弥漫性 SSc 患者中进行的病例对照分析显示，与匹配对照组相比（N=25；-24.0±5.2%对-7.7±4.3%；p=0.03），RTX 组 mRSS 变化更大。此外，与基线相比，RTX 治疗患者在随访时 mRSS 显著降低（26.6±1.4 对 20.3±1.8；p=0.0001）。此外，在间质性肺疾病患者中，与匹配对照组相比，RTX 显著预防了 FVC 的进一步下降（N=9；0.4±4.4%对-7.7±3.6%；p=0.02）。安全性措施与以前在自身免疫性风湿病中的研究一致，表现出良好的特征。
EUSTAR 队列中接受 RTX 治疗与未治疗匹配对照 SSc 患者的比较表明，皮肤纤维化得到改善，肺纤维化恶化得到预防，支持 SSc 中 B 细胞抑制的治疗概念。
