Chen Yiting, Shi Nan, Lei Xin, Ren Pingping, Lan Lan, Chen Liangliang, Wang Yaomin, Xu Ying, Lin Yuxin, Chen Jianghua, Han Fei
Kidney Disease Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Institute of Nephrology, Zhejiang University, Hangzhou, China.
Rheumatology (Oxford). 2025 Jan 1;64(1):221-227. doi: 10.1093/rheumatology/kead674.
Lupus nephritis is a severe and common complication of systemic lupus erythematosus (SLE). The pathogenesis of lupus nephritis is characterized by B-cell activation and autoantibody formation. Rituximab and belimumab, as well as telitacicept, target B cells through different mechanisms, potentially exerting a synergistic effect in the treatment of lupus nephritis. This study aims to investigate the efficacy and safety of treatment with rituximab followed by belimumab or telitacicept in the management of refractory lupus nephritis.
We conducted a single-center, open-label, retrospective study, including 25 patients with refractory lupus nephritis. All patients received combination therapy with rituximab in individualized dosages to achieve peripheral B-cell depletion, and then followed by belimumab or telitacicept. The follow-up period was at least 12 months, and the primary end point was renal remission rate at the last follow-up.
During a median follow-up of 19 (13, 29) months, 20 of 25 (80%) patients achieved objective remission (OR), including 19 (76%) patients achieved complete renal response (CRR). After rituximab (712 ± 416mg in average), 18 patients received belimumab and seven patients received telitacicept. In the rituximab plus telitacicept group, all patients achieved CRR; while in the rituximab plus belimumab group, 12 (66.7%) patients achieved CRR and 13 (72.2%) patients achieved OR. The mean SLEDAI-2K score decreased from 15 ± 6 to 6 ± 6, representing an average reduction of 60%. At the last follow-up, 18/25 (72%) had prednisone ≤ 5 mg/d or even discontinued prednisone use. Adverse effects were mainly immunoglobulin deficiency, respiratory tract infection, urinary tract infections, and rash. No death occurred.
Rituximab followed by belimumab or telitacicept may be effective in inducing remission in refractory lupus nephritis, with tolerable adverse effects.
狼疮性肾炎是系统性红斑狼疮(SLE)严重且常见的并发症。狼疮性肾炎的发病机制以B细胞活化和自身抗体形成为特征。利妥昔单抗、贝利尤单抗以及泰它西普通过不同机制作用于B细胞,在狼疮性肾炎治疗中可能发挥协同效应。本研究旨在探讨利妥昔单抗序贯贝利尤单抗或泰它西普治疗难治性狼疮性肾炎的疗效及安全性。
我们开展了一项单中心、开放标签的回顾性研究,纳入25例难治性狼疮性肾炎患者。所有患者接受个体化剂量的利妥昔单抗联合治疗以实现外周血B细胞清除,随后接受贝利尤单抗或泰它西普治疗。随访期至少12个月,主要终点为末次随访时的肾脏缓解率。
在中位随访19(13,29)个月期间,25例患者中有20例(80%)达到客观缓解(OR),其中19例(76%)达到完全肾脏缓解(CRR)。在使用利妥昔单抗(平均712±416mg)后,18例患者接受贝利尤单抗治疗,7例患者接受泰它西普治疗。在利妥昔单抗联合泰它西普组,所有患者均达到CRR;而在利妥昔单抗联合贝利尤单抗组,12例(66.7%)患者达到CRR,13例(72.2%)患者达到OR。SLEDAI-2K评分均值从15±6降至6±6,平均降低60%。在末次随访时,18/25(72%)患者的泼尼松剂量≤5mg/d,甚至停用了泼尼松。不良反应主要为免疫球蛋白缺乏、呼吸道感染、泌尿系统感染及皮疹。无死亡病例发生。
利妥昔单抗序贯贝利尤单抗或泰它西普可能有效诱导难治性狼疮性肾炎缓解,且不良反应可耐受。