Sfikakis Petros P, Boletis John N, Tsokos George C
First Department of Propedeutic and Internal Medicine, Athens University Medical School, Greece.
Curr Opin Rheumatol. 2005 Sep;17(5):550-7. doi: 10.1097/01.bor.0000172798.26249.fc.
To discuss the clinical effects and the immunologic consequences of transient B-cell depletion using the anti-CD20 monoclonal antibody rituximab in systemic lupus erythematosus.
A total of 100 rituximab-treated patients with severe disease, refractory to major immunosuppressive treatment, have been reported so far. Within a median follow-up period of 12 months rituximab was well tolerated, which is compatible with the experience accumulated from its use in more than 500 000 lymphoma patients. About 80% of patients achieved marked and rapid reductions in global disease activity. Because of the clinical heterogeneity, dosing differences, and concomitant treatments, including cyclophosphamide in 35% of patients, a proper evaluation of the clinical efficacy or rituximab is difficult. Variable degrees of clinical benefit have been reported for all clinical systemic lupus erythematosus manifestations, including active proliferative nephritis. Whereas 4-weekly infusions of 375 mg/m of rituximab result in complete B-cell depletion lasting most often from 3 to 8 months, a prolonged depletion does not always correlate with a more favorable clinical response. Total immunoglobulin levels and protective antibodies are preserved, but anti-dsDNA antibody titers decrease, often independently of the clinical response.
The findings reviewed point to a growing optimism for targeting B cells in the treatment of systemic lupus erythematosus; therefore double-blind studies comparing rituximab with existing immunosuppressive therapies are needed. Moreover, careful assessments of the effects of transient B-cell depletion on distinct autoimmune pathogenetic processes will enable optimization of therapeutic single or combined therapeutic schemes.
探讨使用抗CD20单克隆抗体利妥昔单抗实现系统性红斑狼疮患者B细胞短暂清除后的临床效果及免疫后果。
迄今为止，共报道了100例接受利妥昔单抗治疗的重症患者，这些患者对主要免疫抑制治疗无效。在中位随访期12个月内，利妥昔单抗耐受性良好，这与超过50万淋巴瘤患者使用该药积累的经验相符。约80%的患者实现了整体疾病活动度的显著且快速降低。由于临床异质性、给药差异以及包括35%患者使用环磷酰胺在内的伴随治疗，对利妥昔单抗临床疗效进行恰当评估存在困难。对于包括活动性增殖性肾炎在内的所有系统性红斑狼疮临床症状，均有不同程度临床获益的报道。虽然每4周输注375mg/m²利妥昔单抗通常会导致B细胞完全清除，持续3至8个月，但延长清除时间并不总是与更有利的临床反应相关。总免疫球蛋白水平和保护性抗体得以保留，但抗双链DNA抗体滴度降低，且往往与临床反应无关。
所综述的研究结果表明，在系统性红斑狼疮治疗中针对B细胞的治疗前景愈发乐观；因此需要进行双盲研究，比较利妥昔单抗与现有免疫抑制疗法。此外，仔细评估B细胞短暂清除对不同自身免疫发病机制过程的影响，将有助于优化单一或联合治疗方案。
