Sustained depression of B cell counts in lupus nephritis after treatment with rituximab and/or belimumab is associated with fewer disease flares.

IF 1.9 4区 医学 Q3 RHEUMATOLOGY
Lupus Pub Date : 2024-08-01 Epub Date: 2024-06-11 DOI:10.1177/09612033241260283
Diane Zisa, Jeffrey Zhang-Sun, Paul J Christos, Kyriakos A Kirou
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引用次数: 0

Abstract

Objective: To study the risk of lupus nephritis flare (LNF) or severe lupus flare (SLF) as a function of B cell count kinetics in lupus nephritis (LN) patients after they achieve at least a partial renal response (PRR) with induction treatment that includes rituximab (RTX) and/or belimumab (BLM).

Methods: We performed a retrospective analysis of a cohort of 19 patients with severe LN that received a B cell agent (BCA), RTX and/or BLM, as part of an initial treatment regimen for an LN flare and had subsequent CD19+ B cell measurements in peripheral blood. We then characterized the follow-up periods, after B cell depressions occurred and PRR were achieved, by the corresponding trajectories of B cell counts (BCC). Time periods with sustained low BCC were type 1 (T1) episodes, while those with repletion of BCC>100 cells/μL were called type 2 (T2) episodes. Time periods with rapid BCC repletion, defined as >50 cells/μL in ≤6 months, were called T2b episodes. Corresponding C3, C4, and anti-dsDNA levels were recorded for each episode. The time from PRR until an event, either a LNF or SLF, or to censoring, either at the end of the study period or the end of available patient follow-up, was assessed for each episode type. Kaplan-Meier survival analysis was used to compare time to flare between T1 and T2 episodes.

Results: There were 26 episodes of B cell depression. Seventeen (65%) were T1 and 9 (35%) were T2. Compared to T1 episodes, T2 episodes were 9.0 times more likely to result in flare over the follow-up period (hazard ratio (HR) = 9.0, 95% CI for HR = 2.2-36.7); this risk was even larger for T2b vs T1 episodes. Median BCC was 14 cells/μL in T1 and 160 cells/μL in T2 episodes. Both C3 and C4 levels significantly increased over the duration of the episode in T1 episodes only.

Conclusion: Sustained low BCC was associated with prolonged serologic and clinical response, whereas repletion, and particularly rapid repletion, of B cells after treatment with BCA was associated with subsequent disease flare.

狼疮性肾炎患者在接受利妥昔单抗和/或贝利单抗治疗后,B细胞计数的持续下降与疾病复发的减少有关。
研究目的研究狼疮肾炎(LN)患者在接受包括利妥昔单抗(RTX)和/或贝利单抗(BLM)在内的诱导治疗至少获得部分肾脏反应(PRR)后,狼疮肾炎复发(LNF)或严重狼疮复发(SLF)的风险与B细胞计数动力学的关系:我们对 19 例重度 LN 患者进行了回顾性分析,这些患者接受了 B 细胞制剂 (BCA)、RTX 和/或 BLM,作为 LN 复发的初始治疗方案的一部分,并在随后进行了外周血 CD19+ B 细胞测量。然后,我们根据 B 细胞计数(BCC)的相应轨迹来描述 B 细胞减少和 PRR 实现后的随访期。BCC持续偏低的时间段为1型(T1)事件,而BCC恢复到>100 cells/μL的时间段称为2型(T2)事件。在≤6 个月内 BCC 快速恢复 >50 个细胞/μL 的时间段称为 T2b 期。每次事件都记录了相应的 C3、C4 和抗dsDNA 水平。对每种发作类型评估了从 PRR 到发生事件(LNF 或 SLF)或到剔除(研究期结束或可用患者随访结束)的时间。卡普兰-梅耶生存分析用于比较T1和T2发作的复发时间:结果:共发生 26 次 B 细胞抑制。结果:共发生 26 次 B 细胞抑制,其中 17 次(65%)为 T1,9 次(35%)为 T2。与 T1 期发作相比,T2 期发作在随访期间导致复发的可能性要高出 9.0 倍(危险比 (HR) = 9.0,HR 的 95% CI = 2.2-36.7);T2b 期发作与 T1 期发作相比,风险更大。T1和T2病例的BCC中位数分别为14个细胞/μL和160个细胞/μL。仅在 T1 期中,C3 和 C4 水平在病程中明显升高:结论:持续的低BCC与血清学和临床反应的延长有关,而BCA治疗后B细胞的恢复,尤其是快速恢复,与随后的疾病复发有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Lupus
Lupus 医学-风湿病学
CiteScore
4.20
自引率
11.50%
发文量
225
审稿时长
1 months
期刊介绍: The only fully peer reviewed international journal devoted exclusively to lupus (and related disease) research. Lupus includes the most promising new clinical and laboratory-based studies from leading specialists in all lupus-related disciplines. Invaluable reading, with extended coverage, lupus-related disciplines include: Rheumatology, Dermatology, Immunology, Obstetrics, Psychiatry and Cardiovascular Research…
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