Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Department of Gastroenterology, Dermatology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
Rheumatology (Oxford). 2024 Mar 1;63(3):798-808. doi: 10.1093/rheumatology/kead249.
To identify determinants of neuropsychiatric (NP) flares in patients with SLE treated for active SLE yet no ongoing severe NPSLE with non-biologic standard therapy plus belimumab or placebo.
We analysed data from five phase III trials (BLISS-52, BLISS-76, BLISS-NEA, BLISS-SC, EMBRACE; n = 3638) after exclusion of patients with baseline NP BILAG A. Factors associated with NPSLE flare, defined as a new NP BILAG A or B, were investigated using Cox regression. In a subgroup analysis, we studied patients with baseline NP BILAG E for determinants of de novo NPSLE flare. Organ damage was assessed using the SLICC/ACR Damage Index (SDI).
We documented 105 (2.9%) NPSLE flares. In multivariable analysis, male sex (HR = 2.37; 95% CI: 1.31, 4.28; P = 0.004), baseline NP BILAG B-D (HR = 5.91; 95% CI: 3.86, 9.06; P < 0.001), and increasing SDI scores (HR = 1.35; 95% CI: 1.21, 1.50; P < 0.001) were strongly associated with NPSLE flare. Belimumab use yielded no association at any dose or administration form. In analysis of SDI domains, NP damage was the strongest determinant of NPSLE flare (HR = 3.25; 95% CI: 2.72, 3.88; P < 0.001), holding true for cognitive impairment (HR = 14.29; 95% CI: 9.22, 22.14; P < 0.001), transverse myelitis (HR = 21.89; 95% CI: 5.40, 88.72; P < 0.001), and neuropathy (HR = 8.87; 95% CI: 5.59, 14.09; P < 0.001). Male sex was the strongest determinant of de novo NPSLE flare (HR = 3.26; 95% CI: 1.51, 7.04; P = 0.003).
Male sex, NPSLE history, and NP damage were strong determinants of impending NPSLE flare. No clear protection or predisposition was conferred from add-on belimumab.
在使用非生物标准疗法联合贝利尤单抗或安慰剂治疗活动期系统性红斑狼疮（SLE）但无持续严重神经精神性狼疮（NPSLE）的患者中，确定神经精神性（NP） flares 的决定因素。
我们分析了排除基线 NP BILAG A 的 5 项 III 期试验（BLISS-52、BLISS-76、BLISS-NEA、BLISS-SC 和 EMBRACE）的数据。使用 Cox 回归分析与 NPSLE flares 相关的因素，定义为新的 NP BILAG A 或 B。在亚组分析中，我们研究了基线 NP BILAG E 的患者新发生 NPSLE flares 的决定因素。使用 SLICC/ACR 损伤指数（SDI）评估器官损伤。
我们记录了 105 例（2.9%）NPSLE flares。多变量分析显示，男性（HR=2.37；95%CI：1.31，4.28；P=0.004）、基线 NP BILAG B-D（HR=5.91；95%CI：3.86，9.06；P<0.001）和 SDI 评分升高（HR=1.35；95%CI：1.21，1.50；P<0.001）与 NPSLE flares 密切相关。无论剂量或给药形式如何，贝利尤单抗的使用均与 NPSLE flares 无关。在 SDI 各领域的分析中，NP 损伤是 NPSLE flares 的最强决定因素（HR=3.25；95%CI：2.72，3.88；P<0.001），认知障碍（HR=14.29；95%CI：9.22，22.14；P<0.001）、横贯性脊髓炎（HR=21.89；95%CI：5.40，88.72；P<0.001）和神经病（HR=8.87；95%CI：5.59，14.09；P<0.001）也如此。男性是新发生 NPSLE flares 的最强决定因素（HR=3.26；95%CI：1.51，7.04；P=0.003）。
男性、NPSLE 病史和 NP 损伤是即将发生的 NPSLE flares 的重要决定因素。加用贝利尤单抗没有明显的保护或易感性。
