目的：通过一项随机、双盲、安慰剂对照研究，探讨Sifalimumab对于成人系统性红斑狼疮治疗的有效性及安全性。

方法：本研究共纳入了431名系统性红斑狼疮（SLE）患者，涉及20个国家的107个地方。排除活动性、重症狼疮性肾炎以及伴有神经精神症状的SLE患者。将患者随机分组，分别接受200毫克sifalimumab，600毫克sifalimumab，1200毫克sifalimumab，或安慰剂治疗，给药时间为第1天，第15天和第29天，此后每隔28天给药一次，共给药52周。

结果：基线时期各组研究对象的特征相似，除了安慰剂组患者的病程短，以及600毫克治疗组一小部分患者同时接受霉酚酸酯治疗。在第52周时，所有治疗组符合SLE疾病活动指数2000 (SLEDAI-2K)至少4点改善的主要疗效终点的患者数目，以及无显著恶化的英国狼疮评定组指数（BILAG）得分或医生的全球评估（PGA）明显高于安慰剂组。第24周时治疗效果达到高峰，然后趋于稳定。治疗组中更多的患者其皮肤红斑狼疮面积和严重程度指数评分都有所改善，且治疗组每天糖皮质激素减少至低于7.5毫克的患者比例也高于对照组。

治疗组更多的患者PGA得到了改善，且SLEDAI-2K中减少了≥4点。在600毫克和1200毫克治疗组中，出现耀斑需要糖皮质激素的治疗的患者比例较低。基线时期关节严重受影响的患者中，相比于对照组，治疗组受影响的关节减少的患者人数50%或更多的剂量相关增加。安慰剂组及治疗组的严重不良事件发生率分别为17.6%18.3%。与安慰剂组相比，带状疱疹感染多发于治疗组。

结论：对于成人系统性红斑狼疮的治疗，Sifalimumab是一种很有前景的治疗药物。

附原文：Abstract OBJECTIVES:The efficacy and safety of sifalimumab were assessed in a phase IIb, randomised, double-blind, placebo-controlled study (NCT01283139) of adults with moderate to severe active systemic lupus erythematosus (SLE).METHODS:431 patients were randomised and received monthly intravenous sifalimumab (200?mg, 600?mg or 1200?mg) or placebo in addition to standard-of-care medications. Patients were stratified by disease activity, interferon gene-signature test (high vs low based on the expression of four genes) and geographical region. The primary efficacy end point was the percentage of patients achieving an SLE responder index response at week 52.RESULTS:Compared with placebo, a greater percentage of patients who received sifalimumab (all dosages) met the primary end point (placebo: 45.4%; 200?mg: 58.3%; 600?mg: 56.5%; 1200?mg 59.8%). Other improvements were seen in Cutaneous Lupus Erythematosus Disease Area and Severity Index score (200 mg and 1200?mg monthly), Physician's Global Assessment (600 mg and 1200?mg monthly), British Isles Lupus Assessment Group-based Composite Lupus Assessment (1200?mg monthly), 4-point reductions in the SLE Disease Activity Index-2000 score and reductions in counts of swollen joints and tender joints. Serious adverse events occurred in 17.6% of patients on placebo and 18.3% of patients onsifalimumab. Herpes zoster infections were more frequent with sifalimumab treatment.CONCLUSIONS:Sifalimumab is a promising treatment for adults with SLE. Improvement was consistent across various clinical end points, including global and organ-specific measures of disease activity.

引自：Khamashta M¹, Merrill JT², Werth VP³, Furie R⁴, Kalunian K⁵, Illei GG⁶, Drappa J⁶, Wang L⁷, Greth W⁶; CD1067 study investigators. Sifalimumab, an anti-interferon-α monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 2016 Mar 23. pii: annrheumdis-2015-208562. doi: 10.1136/annrheumdis-2015-208562. [Epub ahead of print]