Department of Medicine, University of Cambridge, Cambridge, UK.
Boehringer Ingelheim International GmbH, Biberach, Germany.
Arthritis Rheumatol. 2023 Nov;75(11):1983-1993. doi: 10.1002/art.42557. Epub 2023 Aug 17.
To characterize its dose-response relationship, BI 655064 (an anti-CD40 monoclonal antibody) was tested as an add-on to mycophenolate and glucocorticoids in patients with active lupus nephritis (LN).
A total of 121 patients were randomized (2:1:1:2) to receive placebo or BI 655064 120, 180, or 240 mg and received a weekly loading dose for 3 weeks followed by dosing every 2 weeks for the 120 and 180 mg groups, and 120 mg weekly for the 240 mg group. The primary endpoint was complete renal response (CRR) at week 52. Secondary endpoints included CRR at week 26.
A dose-response relationship with CRR at week 52 was not shown (BI 655064 120 mg, 38.3%; 180 mg, 45.0%; 240 mg, 44.6%; placebo, 48.3%). At week 26, 28.6% (120 mg), 50.0% (180 mg), 35.0% (240 mg), and 37.5% (placebo) achieved CRR. The unexpected high placebo response prompted a post hoc analysis evaluating confirmed CRR (cCRR, at weeks 46 and 52). cCRR was achieved in 22.5% (120 mg), 44.3% (180 mg), 38.2% (240 mg), and 29.1% (placebo) of patients. Most patients reported ≥1 adverse event (BI 655064, 85.7-95.0%; placebo, 97.5%), most frequently infections and infestations (BI 655064 61.9-75.0%; placebo 60%). Compared with other groups, higher rates of serious (20% vs. 7.5-10%) and severe infections (10% vs. 4.8-5.0%) were reported with 240 mg BI 655064.
The trial failed to demonstrate a dose-response relationship for the primary CRR endpoint. Post hoc analyses suggest a potential benefit of BI 655064 180 mg in patients with active LN.
为了确定其剂量反应关系，我们将抗 CD40 单克隆抗体 BI 655064 作为补充疗法，与霉酚酸酯和糖皮质激素联合用于治疗活动期狼疮肾炎（LN）患者。
共 121 名患者被随机分为（2:1:1:2）安慰剂组和 BI 655064 120、180、240mg 组，患者接受每周一次的负荷剂量治疗 3 周，然后每 2 周给药 1 次，120 和 180mg 组治疗 12 周，240mg 组每周给药 120mg。主要终点为第 52 周时完全肾脏缓解（CRR）。次要终点包括第 26 周时的 CRR。
第 52 周时未显示出与 CRR 相关的剂量反应关系（BI 655064 120mg 组为 38.3%，180mg 组为 45.0%，240mg 组为 44.6%，安慰剂组为 48.3%）。第 26 周时，28.6%（120mg）、50.0%（180mg）、35.0%（240mg）和 37.5%（安慰剂）患者达到 CRR。意外的高安慰剂反应促使我们进行了事后分析，评估了确认的 CRR（第 46 和 52 周时的 cCRR）。22.5%（120mg）、44.3%（180mg）、38.2%（240mg）和 29.1%（安慰剂）的患者达到了 cCRR。大多数患者报告了≥1 次不良事件（BI 655064 组为 85.7-95.0%，安慰剂组为 97.5%），最常见的是感染和寄生虫感染（BI 655064 组为 61.9-75.0%，安慰剂组为 60%）。与其他组相比，240mg BI 655064 组报告的严重（20%比 7.5-10%）和严重感染（10%比 4.8-5.0%）的发生率更高。
该试验未能证明主要的 CRR 终点存在剂量反应关系。事后分析提示 BI 655064 180mg 可能对活动期 LN 患者有益。
