類風濕性關節炎之生物製劑療法 －－ 最新進展

Biologics in the treatment of rheumatoid arthritis: recent advances

類風濕性關節炎是一種慢性發炎的關節疾病，受侵犯的關節滑膜呈現發炎而釋放發炎性細胞激素，導致關節結構包含軟骨及骨骼之破壞，演變為進行性關節破壞。治療類風濕性關節炎的傳統用藥主要為疾病修飾性抗風濕藥物，這類藥物的有限效果及可能副作用使其使用有所局限。儘管類風濕性關節炎的病因仍屬未知，近年來分子生物技術之進步，使吾人得以辨識出導致疾病免疫發炎反應之各式細胞、細胞表面標記及細胞產物。這些進展使吾人對類風濕性關節炎的免疫病因學有更深的了解，進而能針對免疫反應路徑的特殊標的發展出更特定的治療。過去十年來，已有五種生物製劑被用來治療類風濕性關節炎包括有：anakinra, anti-TNF-α agents, rituximab, abatacept, 及tocilizumab。本文針對這些製劑的標的治療機轉及臨床試驗的效益作一討論。

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease with multiple joints involvement. The disease involves inflammation of the synovial membrane, which releases inflammatory cytokines that cause damage to joint components, cartilage and bone, and thus leads to progressive joint destruction. The traditional drugs used for treating RA are known as disease-modifying antirheumatic drugs (DMARDs). The limited efficacy and/or side effects of traditional DMARDs limit their use. Although the etiology of RA remains unknown, recent advances in molecular technology have made it possible to identify distinct cell subsets, cell surface markers, and cell products that contribute to the immune-mediated inflammatory responses associated with the disease. This enhanced understanding of the immunopathogenesis of RA provides opportunities to specifically target the immune response pathways using therapies that are more specific. Over the last decade, five novel biological agents for treatment of RA have already been used in practice or on the horizon: interleukin 1 receptor antagonist (anakinra), anti-TNF agents (infliximab, etanercept, adalimumab), anti-CD20 agent (rituximab), selective T-cell co-stimulation modulator (abatacept), and anti-interleukin 6 receptor (tocilizumab). Here, we briefly discuss the targets of these drugs and the roles of these targets in the pathogenesis of RA and review the efficacy of these drugs from the clinical trial data.