Kanigicherla Durga A K, Kehagia Angie A, Jamshidi Babak, Manounah Lina, Barnes Anna, Patrick Hannah, Powell Helen, Austin Catrin, Norton Stephen, Willcocks Lisa, Griffith Megan, Braddon Fiona, Steenkamp Retha, McKane William S, Khwaja Arif
Manchester Institute of Nephrology and Transplantation, Manchester, UK.
King's College Technology Evaluation Centre (KiTEC), UK.
Clin Kidney J. 2024 Jun 18;17(8):sfae179. doi: 10.1093/ckj/sfae179. eCollection 2024 Aug.
Patients with membranous nephropathy (MN) and poor kidney function or active disease despite previous immunosuppression are underrepresented in clinical trials. It is unknown how effective rituximab is in this population.
This prospective, multi-centre, single-arm, real-world study of patients with active MN [urine protein-creatinine ratio (uPCR) >350 mg/mmol and serum albumin <30 g/L, or a fall in estimated glomerular filtration rate (eGFR) of at least 20% or more over at least 3 months] evaluated rituximab in those with contraindications to calcineurin inhibitors and cytotoxic therapy. The primary outcome was change in rate of eGFR decline before and after rituximab. Complete or partial remission were defined as uPCR <30 mg/mmol or uPCR <350 mg/mmol with a ≥50% fall from baseline, respectively.
A total of 180 patients [median age 59 years, interquartile range (IQR) 48-68] received rituximab and were followed up for a median duration of 17 months. Seventy-seven percent had prior immunosuppression. Median eGFR and uPCR at baseline were 49.2 mL/min/1.73 m (IQR 34.4-80.6) and 766 mg/mmol (IQR 487-1057), respectively. The annual rate of decline of eGFR fell from 13.9 to 1.7 mL/min/1.73 m/year following rituximab (Z score = 2.48, < .0066). At 18 months 12% and 42% of patients were in complete or partial remission, respectively. Rituximab was well tolerated; patient survival was 95.6% at 2 years and in patients in whom eGFR was available, kidney survival was 93% at 2 years.
Rituximab significantly reduced the rate of eGFR decline in active MN including those who had received prior immunosuppression or with poor baseline kidney function.
尽管先前接受过免疫抑制治疗，但患有膜性肾病（MN）且肾功能不佳或疾病仍处于活动期的患者在临床试验中的代表性不足。利妥昔单抗在该人群中的疗效尚不清楚。
这项针对活动性MN患者[尿蛋白肌酐比值（uPCR）>350mg/mmol且血清白蛋白<30g/L，或估计肾小球滤过率（eGFR）在至少3个月内下降至少20%或更多]的前瞻性、多中心、单臂、真实世界研究，评估了对钙调神经磷酸酶抑制剂和细胞毒性疗法有禁忌证的患者使用利妥昔单抗的情况。主要结局是利妥昔单抗治疗前后eGFR下降率的变化。完全缓解或部分缓解分别定义为uPCR<30mg/mmol或uPCR<350mg/mmol且较基线下降≥50%。
共有180例患者[中位年龄59岁，四分位间距（IQR）48 - 68]接受了利妥昔单抗治疗，并进行了中位时长为17个月的随访。77%的患者先前接受过免疫抑制治疗。基线时的中位eGFR和uPCR分别为49.2mL/min/1.73m²（IQR 34.4 - 80.6）和766mg/mmol（IQR 487 - 1057）。利妥昔单抗治疗后，eGFR的年下降率从13.9降至1.7mL/min/1.73m²/年（Z值 = 2.48，P < 0.0066）。在18个月时，分别有12%和42%的患者达到完全缓解或部分缓解。利妥昔单抗耐受性良好；2年时患者生存率为95.6%，在有可用eGFR数据的患者中，2年时肾脏生存率为93%。
利妥昔单抗显著降低了活动性MN患者的eGFR下降率，包括那些先前接受过免疫抑制治疗或基线肾功能不佳的患者。
