Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
Rheumatology (Oxford). 2021 Sep 1;60(9):4348-4354. doi: 10.1093/rheumatology/keaa796.
In light of reports of de novo LN during belimumab (BLM) treatment, we sought to determine its frequency and contributing or protective factors in a real-life setting.
Patients with SLE who received BLM between 2011 and 2017 at five European academic practices were enrolled (n = 95) and followed longitudinally for a median time of 13.1 months [interquartile range (IQR): 6.0-34.7]; 52.6% were anti-dsDNA positive, 60.0% had low complement levels, and 69.5% had no renal involvement prior to/at BLM initiation [mean disease duration at baseline: 11.4 (9.3) years]. Age- and sex-matched patients with non-renal SLE who had similar serological profiles, but were not exposed to BLM, served as controls (median follow-up: 132.0 months; IQR: 98.3-151.2).
We observed 6/66 cases (9.1%) of biopsy-proven de novo LN (4/6 proliferative) among the non-renal BLM-treated SLE cases after a follow-up of 7.4 months (IQR: 2.7-22.2). Among controls, 2/66 cases (3.0%) of de novo LN (both proliferative) were observed after 21 and 50 months. BLM treatment was associated with an increased frequency and/or shorter time to de novo LN [hazard ratio (HR): 10.7; 95% CI: 1.7, 67.9; P = 0.012], while concomitant use of antimalarial agents along with BLM showed an opposing association (HR: 0.2; 95% CI: 0.03, 0.97; P = 0.046).
Addition of BLM to standard-of-care did not prevent LN in patients with active non-renal SLE, but a favourable effect of concomitant use of antimalarials was implicated. Studies of whether effects of B-cell activating factor inhibition on lymphocyte subsets contribute to LN susceptibility are warranted.
鉴于贝利尤单抗（BLM）治疗期间新出现狼疮肾炎（LN）的报道，我们旨在确定其在真实环境中的频率以及相关的致病或保护因素。
在五家欧洲学术机构接受 BLM 治疗的 SLE 患者于 2011 年至 2017 年期间入组（n=95），并进行了中位时间为 13.1 个月[四分位距（IQR）：6.0-34.7]的纵向随访；52.6%患者抗 dsDNA 阳性，60.0%患者补体水平较低，且 69.5%患者在开始 BLM 治疗之前/时无肾脏受累[基线时平均疾病持续时间：11.4（9.3）年]。年龄和性别匹配的非肾脏 SLE 患者具有相似的血清学特征，但未接受 BLM 治疗，作为对照组（中位随访：132.0 个月；IQR：98.3-151.2）。
在非肾脏 BLM 治疗的 SLE 病例中，经过 7.4 个月（IQR：2.7-22.2）的随访，我们观察到 6/66 例（9.1%）活检证实的新发病例 LN（4/6 例为增生性）。在对照组中，在 21 和 50 个月时观察到 2/66 例（3.0%）新发病例 LN（均为增生性）。BLM 治疗与新发病例 LN 的频率增加和/或发病时间缩短相关[风险比（HR）：10.7；95%CI：1.7，67.9；P=0.012]，而 BLM 联合抗疟药物的使用则表现出相反的关联（HR：0.2；95%CI：0.03，0.97；P=0.046）。
在活动期非肾脏 SLE 患者中，BLM 联合标准治疗并未预防 LN，但同时使用抗疟药物具有有利影响。有必要研究 B 细胞激活因子抑制剂对淋巴细胞亚群的影响是否导致 LN 易感性。
