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奥法妥木单抗治疗合并利妥昔单抗诱导血清病的多复发性膜性肾病

Ofatumumab for multirelapsing membranous nephropathy complicated by rituximab-induced serum-sickness.

作者信息

Podestà Manuel Alfredo, Ruggiero Barbara, Remuzzi Giuseppe, Ruggenenti Piero

机构信息

Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy.

Unit of Nephrology and Dialysis, Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy.

出版信息

BMJ Case Rep. 2020 Jan 23;13(1):e232896. doi: 10.1136/bcr-2019-232896.

Abstract

Rituximab (375 mg/m) achieved remission of the first episode and six relapses of nephrotic syndrome (NS) in a young male patient with podocyte phospholipase A receptor (PLAR)-related membranous nephropathy (MN) refractory to steroids and cyclosporine. Between-treatments interval averaged 17.4±4.2 months. The seventh infusion was complicated by delayed serum-sickness, which resolved with steroids. On subsequent relapse, the fully human anti-CD20 monoclonal antibody ofatumumab (300 mg) achieved remission of the NS, without significant side effects. Circulating CD19 B cells were depleted, proteinuria decreased from 10.9 to 1.3 g/day, and serum albumin, immunoglobulin levels and glomerular filtration rate normalised. Twenty-eight months later, despite transient anti-PLAR depletion, ofatumumab (100 mg) failed to induce remission of the eighth relapse. Remission was safely achieved 5 months later with repeated ofatumumab infusion (300 mg). This treatment (€723) was less expensive than rituximab (€1801). Ofatumumab could be a safe and cost/effective rescue therapy for patients with MN sensitised against rituximab.

摘要

利妥昔单抗(375mg/m²)使一名患有足细胞磷脂酶A受体(PLAR)相关膜性肾病(MN)且对类固醇和环孢素耐药的年轻男性患者的首次肾病综合征(NS)发作及6次复发得到缓解。治疗间隔平均为17.4±4.2个月。第七次输注出现了延迟性血清病并发症,使用类固醇后症状缓解。在随后的复发中,全人源抗CD20单克隆抗体奥法木单抗(300mg)使NS得到缓解,且无明显副作用。循环中的CD19 B细胞减少,蛋白尿从10.9g/天降至1.3g/天,血清白蛋白、免疫球蛋白水平及肾小球滤过率恢复正常。28个月后,尽管奥法木单抗(100mg)使PLAR短暂减少,但未能诱导第八次复发缓解。5个月后,重复输注奥法木单抗(300mg)安全地实现了缓解。这种治疗(723欧元)比利妥昔单抗(1801欧元)便宜。奥法木单抗对于对利妥昔单抗敏感的MN患者可能是一种安全且具有成本效益的挽救疗法。

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