Institute of Rheumatology, Department of Connective Tissue Diseases, Warsaw, Poland.
Mini Rev Med Chem. 2010 Sep;10(10):956-65. doi: 10.2174/138955710792007187.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease of unknown etiology and limited available therapeutic options frustrating both clinicians and patients. However, recent advances in the understanding of disease mechanisms have given rise to numerous studies on specific approaches to SLE treatment. The purpose of this review is to explain the rationale for new treatments and results of the first clinical studies. We will focus on agents which deplete B cells (anti-CD20, anti-CD22), block cytokines (TNF α, Il 6), inhibit B/T cells interaction (CTLA-4Ig, anti-CD40L), or are even expected to reconstruct physiologic immunotolerance. Although preliminary results seemed promising, two randomized clinical trials with rituximab (EXPLORER and LUNAR study) failed to prove efficacy. Data analysis continues to explain the reasons. Trial design, subject population, limitations of the outcome measure instrument and site qualification have been questioned. Future studies are likely to focus on specific organ involvement or treatment combinations with other immunosuppressive agents.
系统性红斑狼疮（SLE）是一种病因不明且治疗选择有限的复杂自身免疫性疾病，令临床医生和患者都感到沮丧。然而，对疾病机制的理解的最新进展为 SLE 治疗的特定方法的研究提供了许多机会。本文旨在解释新治疗方法的原理和首批临床研究的结果。我们将重点介绍可清除 B 细胞的药物（抗 CD20、抗 CD22）、阻断细胞因子的药物（TNFα、IL-6）、抑制 B/T 细胞相互作用的药物（CTLA-4Ig、抗 CD40L），甚至预期能重建生理性免疫耐受的药物。尽管初步结果似乎很有希望，但两项利妥昔单抗（EXPLORER 和 LUNAR 研究）的随机临床试验未能证明其疗效。数据分析仍在继续解释原因。试验设计、受试人群、疗效评估工具的局限性和研究机构的资质等问题受到了质疑。未来的研究可能会集中在特定器官受累或与其他免疫抑制剂联合治疗上。
