Pers Yves Marie, Jorgensen Christian
Inserm, U1183, Hôpital Saint-Eloi, Montpellier, F-34295 France.
Université MONTPELLIER, UFR de Médecine, Montpellier, F-34000 France.
Immunotherapy. 2016 Sep;8(9):1091-6. doi: 10.2217/imt-2016-0003.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune condition viewed as a severe destructive disease. The treatment strategies include anti-CD20 monoclonal antibody (mAb)-targeting B cells. Ofatumumab specifically targets a membrane-proximal epitope on the CD20 molecule distinct from other anti-CD20 antibodies including rituximab and ocrelizumab, and bind the epitope located on the large loop of CD20. This explains a more durable B-cell depletion and a different pharmacodynamic. We review the pharmacodynamic of B-cell depletion and analyze the results in RA and other B-cell-mediated autoimmune diseases. The randomized trial in RA showed clinical efficacy comparable to rituximab at week 24. However, structural impact has not been demonstrated. Studies including RA patients refractory to rituximab would be useful to define the optimal strategy of ofatumumab therapy.
类风湿性关节炎(RA)是一种慢性炎症性自身免疫性疾病,被视为一种严重的破坏性疾病。治疗策略包括靶向B细胞的抗CD20单克隆抗体(mAb)。奥法木单抗特异性靶向CD20分子上一个与包括利妥昔单抗和奥瑞珠单抗在内的其他抗CD20抗体不同的膜近端表位,并结合位于CD20大环上的表位。这解释了更持久的B细胞耗竭和不同的药效学。我们综述了B细胞耗竭的药效学,并分析了在类风湿性关节炎和其他B细胞介导的自身免疫性疾病中的结果。类风湿性关节炎的随机试验显示,在第24周时临床疗效与利妥昔单抗相当。然而,尚未证明其对结构的影响。纳入对利妥昔单抗难治的类风湿性关节炎患者的研究,将有助于确定奥法木单抗治疗的最佳策略。