類風濕性關節炎免疫生物製劑治療之新進展

Update on the Treatment of Rheumatoid Arthritis with Immune Biological Agents

類風濕性關節炎（rheumatoid arthritis）是一種以關節滑膜組織發炎和關節破壞為主要特徵的自體免疫疾病，雖然類風濕性關節炎的致病機轉尚不是很清楚，但是最近研究顯示T 淋巴細胞（尤其是TH17 細胞）、B 淋巴細胞和細胞激素在類風濕性關節炎的致病機轉扮演很重要角色，因此最近幾年許多以免疫細胞和細胞激素為標靶的生物製劑藥物陸續被研發出來治療類風濕性關節炎。Etanercept （EnbrelÒ）、adalimumab （HumiraÒ）、golimumab （SimponiÒ）、infliximab （RemicadeÒ）和certolizumab pegol （CimziaÒ）是屬於抑制TNF-α作用的生物製劑，anakinra （KineretÒ）和tocilizumab （ActemraÒ）分別是對抗IL-1 和IL-6 的生物製劑，aAbatacept （OrenciaÒ）可以阻斷CD28 和B7 分子的結合而達到抑制T 淋巴細胞活化的作用，rituximab （MabtheraÒ）是一種認識B 淋巴細胞表面抗原CD20 的抗體，因此rituxima 可以在體內造成B 淋巴細胞的清除而達到抑制B 淋巴細胞功能的作用。這些生物製劑可以調節免疫細胞和細胞激素的功能而達到控制關節炎的效果，在臨床試驗也證實這些生物製劑對許多類風濕性關節炎的病人有良好的療效，將來應該會有更多新的針對不同免疫細胞和分子的免疫標靶生物製劑被開發來治療類風濕性關節炎。

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis and joint destruction. Although the pathogenesis of RA remains to be clarified, recent studies have demonstrated that T cells (especially TH17 cells), B cells and certain cytokines critically regulate the joint inflammation in RA. Thus, several biological agents that target T cells, B cells and cytokines have been developed to treat RA. Etanercept (Enbrel), adalimumab (Humira), golimumab (Simponi), infliximab (Remicade) and certolizumab pegol (Cimzia) belong to the class of anti-TNF biological agents that can antagonize the pro-inflammatory functions of TNF-alpha. Anakinra (Kineret) and tocilizumab (Actemra) are biological agents that can block the actions of IL-1 and IL-6, respectively. Abatacept (Orencia) interferes with T cell activation by interrupting the interaction between CD28 and B7 molecules. Rituximab (Mabthera) is an anti-CD20 antibody that causes B cell depletion in vivo and therefore reduces the B cell functions. All these biological agents have been proved to be effective in the RA treatment in clinical trials. More biological agents or molecules that target different components of immune responses and cytokine signaling may be coming to treat RA in the future.