Scolari Francesco, Delbarba Elisa, Santoro Domenico, Gesualdo Loreto, Pani Antonello, Dallera Nadia, Mani Laila-Yasmin, Santostefano Marisa, Feriozzi Sandro, Quaglia Marco, Boscutti Giuliano, Ferrantelli Angelo, Marcantoni Carmelita, Passerini Patrizia, Magistroni Riccardo, Alberici Federico, Ghiggeri Gian Marco, Ponticelli Claudio, Ravani Pietro
Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
Nephrology Unit, Spedali Civili Hospital, ASST Spedali Civili of Brescia, Brescia, Italy.
J Am Soc Nephrol. 2021 Apr;32(4):972-982. doi: 10.1681/ASN.2020071091. Epub 2021 Mar 1.
A cyclic corticosteroid-cyclophosphamide regimen is the first-line therapy for membranous nephropathy. Compared with this regimen, rituximab therapy might have a more favorable safety profile, but a head-to-head comparison is lacking.
We randomly assigned 74 adults with membranous nephropathy and proteinuria >3.5 g/d to rituximab (1 g) on days 1 and 15, or a 6-month cyclic regimen with corticosteroids alternated with cyclophosphamide every other month. The primary outcome was complete remission of proteinuria at 12 months. Other outcomes included determination of complete or partial remission at 24 months and occurrence of adverse events.
At 12 months, six of 37 patients (16%) randomized to rituximab and 12 of 37 patients (32%) randomized to the cyclic regimen experienced complete remission (odds ratio [OR], 0.4; 95% CI, 0.13 to 1.23); 23 of 37 (62%) receiving rituximab and 27 of 37 (73%) receiving the cyclic regimen had complete or partial remission (OR, 0.61; 95% CI, 0.23 to 1.63). At 24 months, the probabilities of complete and of complete or partial remission with rituximab were 0.42 (95% CI, 0.26 to 0.62) and 0.83 (95% CI, 0.65 to 0.95), respectively, and 0.43 (95% CI, 0.28 to 0.61) and 0.82 (95% CI, 0.68 to 0.93), respectively, with the cyclic regimen. Serious adverse events occurred in 19% of patients receiving rituximab and in 14% receiving the cyclic regimen.
This pilot trial found no signal of more benefit or less harm associated with rituximab versus a cyclic corticosteroid-cyclophosphamide regimen in the treatment of membranous nephropathy. A head-to-head, pragmatic comparison of the cyclic regimen versus rituximab may require a global noninferiority trial.
Rituximab versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO), NCT03018535.
环磷酰胺联合糖皮质激素的周期性治疗方案是膜性肾病的一线治疗方法。与该方案相比，利妥昔单抗治疗可能具有更良好的安全性，但缺乏直接比较。
我们将74例蛋白尿>3.5g/d的成年膜性肾病患者随机分为两组，一组在第1天和第15天接受利妥昔单抗（1g）治疗，另一组接受为期6个月的周期性治疗方案，即糖皮质激素与环磷酰胺每隔一个月交替使用。主要结局是12个月时蛋白尿完全缓解。其他结局包括确定24个月时的完全或部分缓解情况以及不良事件的发生情况。
在12个月时，随机分配至利妥昔单抗组的37例患者中有6例（16%）实现完全缓解，随机分配至周期性治疗方案组的37例患者中有12例（32%）实现完全缓解（优势比[OR]为0.4；95%置信区间为0.13至1.23）；接受利妥昔单抗治疗的37例患者中有23例（62%）、接受周期性治疗方案的37例患者中有27例（73%）实现完全或部分缓解（OR为0.61；95%置信区间为0.23至1.63）。在24个月时，利妥昔单抗组完全缓解以及完全或部分缓解的概率分别为0.42（95%置信区间为0.26至0.62）和0.83（95%置信区间为0.65至0.95），周期性治疗方案组分别为0.43（95%置信区间为0.28至0.61）和0.82（95%置信区间为0.68至0.93）。接受利妥昔单抗治疗的患者中有19%发生严重不良事件，接受周期性治疗方案的患者中有14%发生严重不良事件。
这项初步试验发现，在治疗膜性肾病方面，与环磷酰胺联合糖皮质激素的周期性治疗方案相比，利妥昔单抗并无更多益处或更少危害的迹象。对周期性治疗方案与利妥昔单抗进行直接、实用的比较可能需要一项全球性非劣效性试验。
利妥昔单抗与类固醇及环磷酰胺治疗特发性膜性肾病（RI-CYCLO），NCT03018535。
