Division of Allergy, Immunology and Rheumatology, University of Rochester School of Medicine, Rochester, New York, USA.
Curr Opin Rheumatol. 2012 Sep;24(5):451-6. doi: 10.1097/BOR.0b013e32835707e4.
Last year was marked by important clinical and mechanistic studies that improved our understanding of B-cell immunotherapy for systemic lupus erythematosus (SLE) and Sjogren's syndrome. Here, we will highlight the most relevant studies published in the last 18 months.
The highlight of the year was the approval of belimumab on the basis of two major trials. On the flip side, the disappointing results of rituximab in lupus nephritis provided a clinical and mechanistic counterpoint in SLE. Still, major limitations in the LUpus Nephritis Assessment with Rituximab (LUNAR) trial, positive subset analysis and new open studies and registries continue to provide hope for and major insights into the use of B-cell depletion. In Sjogren's syndrome, the role of B-cell depletion has been further investigated, both for glandular and extraglandular manifestations of the disease with mixed results in a disease in which outcomes are notoriously hard to measure.
The approval of anti-B cell activating factor therapy and an increasing body of open studies with rituximab as well as subset studies and secondary analysis of the Efficacy and Safety of Rituximab in Moderately-to-Severely Active Systemic Lupus Erythematosus (EXPLORER) and LUNAR trials provide hope for B-cell immunotherapy and significant insight into its mechanisms of action and utilization in a selected subset of patients. Ongoing clinical trials of other B-cell targeting agents are eagerly anticipated.
去年的重要临床和机制研究提高了我们对系统性红斑狼疮(SLE)和干燥综合征的 B 细胞免疫治疗的理解。在此,我们将重点介绍过去 18 个月发表的最相关的研究。
今年的亮点是基于两项主要试验批准了贝利尤单抗。另一方面,利妥昔单抗治疗狼疮肾炎的令人失望的结果为 SLE 提供了临床和机制上的对比。尽管如此,LUpus Nephritis Assessment with Rituximab(LUNAR)试验、阳性亚组分析以及新的开放研究和登记处仍存在重大局限性,这些为 B 细胞耗竭的应用提供了希望和重要的见解。在干燥综合征中,B 细胞耗竭的作用得到了进一步的研究,无论是在疾病的腺体还是腺体外表现方面,结果都喜忧参半,因为在这种疾病中,结果很难衡量。
抗 B 细胞激活因子治疗的批准,以及越来越多的利妥昔单抗开放研究,以及 EXPLORER 和 LUNAR 试验的亚组研究和次级分析,为 B 细胞免疫治疗提供了希望,并对其作用机制及其在选定患者亚组中的应用有了重要的了解。其他 B 细胞靶向药物的临床试验正在进行中,人们对此充满期待。