Rheumatology Unit, Department of Medicine D, University Hospital Münster, Domagkstr. 3a, 48149 Münster, Germany.
Curr Opin Pharmacol. 2010 Jun;10(3):316-21. doi: 10.1016/j.coph.2010.02.002. Epub 2010 Feb 26.
Although B cells represent major contributors to rheumatoid arthritis (RA) pathogenesis, their precise roles in the induction and maintenance of abnormal immune activation in this entity remains poorly understood. As proof of principle, rituximab, a chimeric B cell depleting anti-CD20-antibody, has demonstrated that depletion of B cells can substantially improve signs and symptoms as well as physical function and inhibit radiologic progression that led to the approval of this agent to treat patients with moderate to severe RA lacking response to TNF-alpha blocking agents in 2006. Placebo-controlled clinical trials as well as subsequent studies and experiences further contributed to our understanding of the mechanism of action of rituximab, but a number of open questions remain. This review summarizes some lessons learned from B cell depletion in RA including particular safety aspects. Of importance using this therapy is that it apparently provides the highest likelihood of response in seropositive RA patients. This observation differentiates it from other currently available therapies and closes the conceptual loop that the underlying immunopathogenesis involves B cells requiring 'targeted' therapy.
尽管 B 细胞是类风湿关节炎 (RA) 发病机制的主要贡献者，但它们在该疾病中诱导和维持异常免疫激活的确切作用仍知之甚少。作为原理证明，利妥昔单抗是一种嵌合的 B 细胞耗竭抗 CD20 抗体，已证明 B 细胞耗竭可显著改善体征和症状以及身体功能，并抑制影像学进展，这导致该药物于 2006 年被批准用于治疗对 TNF-α 阻断剂无反应的中重度 RA 患者。安慰剂对照临床试验以及随后的研究和经验进一步帮助我们了解了利妥昔单抗的作用机制，但仍存在许多悬而未决的问题。这篇综述总结了从 RA 中的 B 细胞耗竭中获得的一些经验教训，包括特定的安全性方面。使用这种疗法的重要性在于，它显然在血清阳性 RA 患者中提供了最高的应答可能性。这一观察结果将其与其他目前可用的疗法区分开来，并封闭了一个概念循环，即潜在的免疫发病机制涉及需要“靶向”治疗的 B 细胞。
