Huang Li, Huang Yingzi, Zeng Jiamin, Zhang Huhai, Chen Liping, Li Yi, Zhao Hongwen, Tang Xiaopeng
Nephrology Department, The First Affiliated Hospital of Army Medical University, Chongqing, China.
Front Med (Lausanne). 2025 Aug 22;12:1608085. doi: 10.3389/fmed.2025.1608085. eCollection 2025.
Biological agents targeting B-cell pathways represent significant advances in systemic lupus erythematosus (SLE) management, yet optimal patient selection remains challenging. This study evaluated whether BAFF/APRIL expression testing could guide personalized treatment decisions in SLE patients.
In this real-world observational study, we compared two treatment strategies in 86 SLE patients: personalized therapy with telitacicept in BAFF/APRIL double-positive patients ( = 14) versus conventional belimumab therapy without expression testing ( = 72). Clinical responses, laboratory parameters, and steroid-sparing effects were assessed at 3 and 6 months.
Despite having significantly higher baseline disease activity (SLEDAI 18.79 ± 9.34 vs. 8.86 ± 4.3) and more severe proliferative lupus nephritis (Class IV/IV + V in 78.6% vs. 52.8%), the BAFF/APRIL-guided telitacicept group achieved higher complete response rates (57.1% vs. 48.6%) and lower non-response rates (7.1% vs. 23.6%) compared to the conventional belimumab group. The BAFF/APRIL-guided group showed more substantial improvements in complement C3 levels (Δ = 0.49 vs. 0.24, < 0.001) and anti-dsDNA antibody reduction (Δ = -177.07 vs -117.00, = 0.028) at 6 months. Notably, normalization of immunological parameters was significantly better in the personalized therapy group, with dsDNA abnormalities decreasing from 92.9 to 7.1% (vs 91.7-32.5%) and C3 abnormalities from 100 to 28.6% (vs 91.7-61.1%). The BAFF/APRIL-guided group also achieved greater steroid dose reduction at 6 months (Δ = -35.00 vs -25.00 mg, = 0.014).
BAFF/APRIL expression-guided telitacicept therapy demonstrated superior efficacy in improving clinical responses and laboratory parameters in SLE patients compared to conventional belimumab therapy, despite treating patients with more severe baseline disease. This real-world study provides preliminary evidence supporting BAFF/APRIL testing as a potential biomarker-driven approach for personalized SLE management, warranting further prospective validation.
靶向B细胞通路的生物制剂代表了系统性红斑狼疮（SLE）治疗的重大进展，但最佳患者选择仍然具有挑战性。本研究评估了BAFF/APRIL表达检测是否可以指导SLE患者的个性化治疗决策。
在这项真实世界观察性研究中，我们比较了86例SLE患者的两种治疗策略：对BAFF/APRIL双阳性患者（n = 14）采用替利西普进行个性化治疗，与未进行表达检测的传统贝利尤单抗治疗（n = 72）。在3个月和6个月时评估临床反应、实验室参数和激素节省效果。
尽管BAFF/APRIL引导的替利西普组基线疾病活动度显著更高（SLEDAI 18.79±9.34 vs. 8.86±4.3）且增殖性狼疮肾炎更严重（IV/IV + V级分别为78.6% vs. 52.8%），但与传统贝利尤单抗组相比，其完全缓解率更高（57.1% vs. 48.6%），无反应率更低（7.1% vs. 23.6%）。在6个月时，BAFF/APRIL引导组的补体C3水平改善更显著（Δ = 0.49 vs. 0.24，P < 0.001），抗双链DNA抗体降低更明显（Δ = -177.07 vs -117.00，P = 0.028）。值得注意的是，个性化治疗组免疫参数的正常化明显更好，双链DNA异常从92.9%降至7.1%（vs 91.7 - 32.5%），C3异常从100%降至28.6%（vs 91.7 - 61.1%）。BAFF/APRIL引导组在6个月时也实现了更大幅度的激素剂量减少（Δ = -35.00 vs -25.00 mg，P = 0.014）。
与传统贝利尤单抗治疗相比，BAFF/APRIL表达引导的替利西普治疗在改善SLE患者的临床反应和实验室参数方面显示出更高的疗效，尽管治疗的是基线疾病更严重的患者。这项真实世界研究提供了初步证据，支持将BAFF/APRIL检测作为一种潜在的生物标志物驱动方法用于SLE的个性化管理，值得进一步进行前瞻性验证。
