Sinha Aditi, Mathew Georgie, Arushi Arushi, Govindarajan Srinivasavaradan, Ghanapriya Kshetrimayum, Grewal Neetu, Rai Khushboo, Brijwal Megha, Kalluru Sree Laya, Tewari Prachi, Misra Angeli, Khandelwal Priyanka, Hari Pankaj, Bagga Arvind
Division of Nephrology and ICMR Center for Advanced Research in Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
Division of Pediatric Nephrology, Department of Child Health, Christian Medical College, Vellore, Tamil Nadu, India.
Nephrol Dial Transplant. 2023 Mar 31;38(4):939-949. doi: 10.1093/ndt/gfac228.
Sequential rituximab (RTX) administration has emerged as an important strategy to sustain remission of disease in patients with difficult-to-treat nephrotic syndrome.
We report the efficacy and safety of sequential therapy with two or more courses of intravenous RTX in 250 patients with difficult-to-treat steroid dependence (n = 127) and calcineurin inhibitor (CNI)-dependent or CNI-refractory steroid resistance (n = 123) managed at one center during 2015-2021. Subsets of patients were cross-sectionally tested for hypogammaglobulinemia, seroprotection against and hyporesponsiveness to vaccines for hepatitis B and tetanus, BK/JC viruria and human antichimeric antibodies (HACAs).
Sequential RTX therapy, initiated at a median of 10 years [interquartile range (IQR) 7.3-14.4], was administered for 1.8 courses/person-year [95% confidence interval (CI) 1.7-2.0] over 2.0 years (95% CI 1.2-3.0). Therapy was associated with postponement of relapses by a median of 3 years in patients with steroid-sensitive disease and 2 years in those with steroid resistance. Relapses were reduced by a mean of 2.0 relapses/person-year (95% CI 1.8-2.2), enabling a reduction in prednisolone dose to 0.04 mg/kg/day (95% CI 0.01-0.11) and withdrawal of additional immunosuppression in 154 (62%) patients. RTX-associated adverse events, occurring at 0.20 events/person-year (95% CI 0.17-0.23), were chiefly comprised of infusion reactions (n = 108) and infections (n = 46); serious adverse events were observed in 10.8% patients, at 0.03 events/person-year (95% CI 0.02-0.05). Hypogammaglobulinemia was observed in 35% of 177 patients and was moderate to severe in 8.5% of cases. Rates of seroprotection at baseline and response following vaccination were lower for hepatitis B [1.9% and 29.4% (n = 52)] than tetanus [65.5% and 34.5% (n = 58)]. BK/JC viruria, without viremia, was observed in 7.3% of 109 cases. A total of 19 of 107 patients (17.8%) had HACAs, which were associated with B cell nondepletion and serum sickness. Age at therapy of <9-10 years was associated with a risk of early relapse, treatment failure and hypogammaglobulinemia following RTX therapy.
Sequential therapy with RTX effectively reduces relapses in patients with difficult-to-treat steroid- and/or CNI-dependent or CNI-refractory nephrotic syndrome. Therapy is associated with high rates of hypogammaglobulinemia and infusion reactions.
序贯利妥昔单抗（RTX）给药已成为维持难治性肾病综合征患者疾病缓解的重要策略。
我们报告了2015年至2021年期间在一个中心接受治疗的250例难治性类固醇依赖患者（n = 127）和钙调神经磷酸酶抑制剂（CNI）依赖或CNI难治性类固醇抵抗患者（n = 123）接受两个或更多疗程静脉注射RTX序贯治疗的疗效和安全性。对部分患者进行横断面检测，以评估低丙种球蛋白血症、乙肝和破伤风疫苗的血清保护及低反应性、BK/JC病毒尿和人抗嵌合抗体（HACA）。
序贯RTX治疗开始于中位时间10年[四分位间距（IQR）7.3 - 14.4]，在2.0年（95%置信区间[CI] 1.2 - 3.0）内每人每年给予1.8个疗程[95% CI 1.7 - 2.0]。该治疗使类固醇敏感疾病患者的复发推迟中位时间3年，类固醇抵抗患者推迟2年。复发平均减少2.0次/人年（95% CI 1.8 - 2.2），使泼尼松龙剂量降至0.04 mg/kg/天（95% CI 0.01 - 0.11），并使154例（62%）患者停用其他免疫抑制剂。RTX相关不良事件发生率为0.20次/人年（95% CI 0.17 - 0.
