Pendergraft William F, Cortazar Frank B, Wenger Julia, Murphy Andrew P, Rhee Eugene P, Laliberte Karen A, Niles John L
Joint Nephrology Fellowship Program, Brigham and Women's Hospital and Massachusetts General Hospital, Boston, Massachusetts, †Division of Nephrology, Department of Medicine,, ‡Vasculitis and Glomerulonephritis Clinic, Division of Nephrology, and, §Categorical Internal Medicine Residency Program, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Clin J Am Soc Nephrol. 2014 Apr;9(4):736-44. doi: 10.2215/CJN.07340713. Epub 2014 Mar 13.
Remission in the majority of ANCA vasculitis patients is not sustained after a single course of rituximab, and risk of relapse warrants development of a successful strategy to ensure durable remission.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A retrospective analysis of ANCA vasculitis patients who underwent maintenance therapy using rituximab-induced continuous B-cell depletion for up to 7 years was performed. Maintenance therapy with rituximab was initiated after achieving remission or converting from other prior maintenance therapy. Continuous B-cell depletion was achieved in all patients by scheduled rituximab administration every 4 months. Disease activity, serologic parameters, adverse events, and survival were examined.
In the study, 172 patients (mean age=60 years, 55% women, 57% myeloperoxidase-ANCA) treated from April of 2006 to March of 2013 underwent continuous B-cell depletion with rituximab. Median remission maintenance follow-up time was 2.1 years. Complete remission (Birmingham Vasculitis Activity Score [BVAS] = 0) was achieved in all patients. Major relapse (BVAS ≥ 3) occurred in 5% of patients and was associated with weaning of other immunosuppression drugs. Remission was reinduced in all patients. Survival mirrored survival of a general age-, sex-, and ethnicity-matched United States population.
This analysis provides evidence for long-term disease control using continuous B-cell depletion. This treatment strategy in ANCA vasculitis patients also seems to result in survival rates comparable with rates in a matched reference population. These findings suggest that prospective remission maintenance treatment trials using continuous B-cell depletion are warranted.
大多数抗中性粒细胞胞浆抗体(ANCA)血管炎患者在接受单疗程利妥昔单抗治疗后,缓解状态无法持续,复发风险促使人们制定成功策略以确保持久缓解。
设计、研究地点、参与者及测量指标:对接受利妥昔单抗诱导的持续B细胞清除维持治疗长达7年的ANCA血管炎患者进行回顾性分析。在达到缓解或从其他先前维持治疗转换后开始使用利妥昔单抗进行维持治疗。通过每4个月定期给予利妥昔单抗,使所有患者实现持续B细胞清除。检查疾病活动度、血清学参数、不良事件和生存率。
在该研究中,2006年4月至2013年3月期间治疗的172例患者(平均年龄60岁,55%为女性,57%为髓过氧化物酶-ANCA)接受了利妥昔单抗诱导的持续B细胞清除治疗。缓解维持的中位随访时间为2.1年。所有患者均实现完全缓解(伯明翰血管炎活动评分[BVAS]=0)。5%的患者发生主要复发(BVAS≥3),且与其他免疫抑制药物的撤减有关。所有患者均再次诱导缓解。生存率与年龄、性别和种族匹配的美国普通人群的生存率相当。
该分析为使用持续B细胞清除进行长期疾病控制提供了证据。ANCA血管炎患者的这种治疗策略似乎也能使生存率与匹配的参考人群相当。这些发现表明,有必要进行使用持续B细胞清除的前瞻性缓解维持治疗试验。