B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial.
B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial.
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DOI：
10.1136/annrheumdis-2021-220920
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发表时间：
2022-01
影响因子：
27.4
通讯作者：
Malvar A
中科院分区：
文献类型：
--
作者：
Furie RA;Aroca G;Cascino MD;Garg JP;Rovin BH;Alvarez A;Fragoso-Loyo H;Zuta-Santillan E;Schindler T;Brunetta P;Looney CM;Hassan I;Malvar A
I型抗CD 20抗体利妥昔单抗和ocrelizumab的随机试验未能显示增殖性狼疮肾炎（LN）的益处。我们比较了obinutuzumab（一种诱导有效B细胞耗竭的人源化II型抗CD 20单克隆抗体）与安慰剂联合标准疗法治疗LN。接受麦考酚酯和皮质类固醇的LN患者在第1天和第2、24和26周随机接受obinutuzumab 1000 mg或安慰剂，并随访至第104周。主要终点为第52周时的完全肾脏缓解（CRR）。进行了至第104周的探索性分析。预先设定的α水平为0.2。共125例患者接受随机化并接受盲态输注。第52周时，obinutuzumab组达到的CRR更高（主要终点，22例（35%）vs安慰剂组14例（23%）;百分比差异，12%）（95% CI −3.4%至28%），p=0.115）和第104周（26（41%）vs 14（23%）;百分比差异，19%（95% CI 2.7%至35%），p=0.026）。obinutuzumab组在其他肾反应指标、血清学、估计肾小球滤过率和蛋白尿方面的改善更大。Obinutuzumab与严重不良事件、严重感染或死亡的增加无关。Obinutuzumab组的非严重输注相关反应发生率更高。在接受obinutuzumab加标准疗法的LN患者中，与单独标准疗法相比，观察到第104周的肾反应改善。Obinutuzumab耐受性良好，未发现新的安全性信号。 NCT 02550652。
Randomised trials of type I anti-CD20 antibodies rituximab and ocrelizumab failed to show benefit in proliferative lupus nephritis (LN). We compared obinutuzumab, a humanised type II anti-CD20 monoclonal antibody that induces potent B-cell depletion, with placebo for the treatment of LN in combination with standard therapies. Patients with LN receiving mycophenolate and corticosteroids were randomised to obinutuzumab 1000 mg or placebo on day 1 and weeks 2, 24 and 26, and followed through week 104. The primary endpoint was complete renal response (CRR) at week 52. Exploratory analyses through week 104 were conducted. The prespecified alpha level was 0.2. A total of 125 patients were randomised and received blinded infusions. Achievement of CRR was greater with obinutuzumab at week 52 (primary endpoint, 22 (35%) vs 14 (23%) with placebo; percentage difference, 12% (95% CI −3.4% to 28%), p=0.115) and at week 104 (26 (41%) vs 14 (23%); percentage difference, 19% (95% CI 2.7% to 35%), p=0.026). Improvements in other renal response measures, serologies, estimated glomerular filtration rate and proteinuria were greater with obinutuzumab. Obinutuzumab was not associated with increases in serious adverse events, serious infections or deaths. Non-serious infusion-related reactions occurred more frequently with obinutuzumab. Improved renal responses through week 104 were observed in patients with LN who received obinutuzumab plus standard therapies compared with standard therapies alone. Obinutuzumab was well tolerated and no new safety signals were identified. NCT02550652.
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影响因子：
4.7
作者：
Hahn, Bevra H.;McMahon, Maureen A.;Wilkinson, Alan;Wallace, W. Dean;Daikh, David I.;Fitzgerald, John D.;Karpouzas, George A.;Merrill, Joan T.;Wallace, Daniel J.;Yazdany, Jinoos;Ramsey-Goldman, Rosalind;Singh, Karandeep;Khalighi, Mazdak;Choi, Soo-In;Gogia, Maneesh;Kafaja, Suzanne;Kamgar, Mohammad;Lau, Christine;Martin, William J.;Parikh, Sefali;Peng, Justin;Rastogi, Anjay;Chen, Weiling;Grossman, Jennifer M.
通讯作者：
Grossman, Jennifer M.
DOI：
10.1093/rheumatology/kex067
发表时间：
2017-07-01
期刊：
Rheumatology (Oxford, England)
影响因子：
--
作者：
Reddy V;Klein C;Isenberg DA;Glennie MJ;Cambridge G;Cragg MS;Leandro MJ
通讯作者：
Leandro MJ
影响因子：
158.5
作者：
Furie, Richard;Rovin, Brad H.;Roth, David A.
通讯作者：
Roth, David A.
影响因子：
--
作者：
Rovin, Brad H.;Furie, Richard;Appel, Gerald
通讯作者：
Appel, Gerald
影响因子：
2.6
作者：
Pejsa, Vlatko;Lucijanic, Marko;Mitrovic, Zdravko
通讯作者：
Mitrovic, Zdravko