Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis.
Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis.
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I型干扰素抑制剂阳离子的I阶段随机试验对活性狼疮性肾炎患者。
DOI：
10.1136/annrheumdis-2021-221478
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发表时间：
2022-04
影响因子：
27.4
通讯作者：
Lindholm C
中科院分区：
文献类型：
--
作者：
Jayne D;Rovin B;Mysler EF;Furie RA;Houssiau FA;Trasieva T;Knagenhjelm J;Schwetje E;Chia YL;Tummala R;Lindholm C
评估I型干扰素受体抗体（anifrolumab）在活动性、活检证实的III/IV类狼疮性肾炎患者中的疗效和安全性。这项II期双盲研究将147例患者（1：1：1）随机分配至每月一次静脉注射阿尼夫鲁单抗基础方案（BR，300 mg）、强化方案（IR，900 mg ×3，此后300 mg）或安慰剂，同时接受标准治疗（口服糖皮质激素、吗替麦考酚酯）。主要终点是合并的阿尼福鲁单抗组与安慰剂组在第52周（W）时基线24小时尿蛋白-肌酐比值（UPCR）的变化。次要终点为第52周时的完全肾脏缓解（CRR）。探索性终点包括更严格的CRR定义和持续糖皮质激素减量（≤7.5 mg/天，W24-52）。安全性进行了分析。患者接受了阿尼夫鲁单抗BR（n=45）、IR（n=51）或安慰剂（n=49）。在第52周，联合阿尼福鲁单抗和安慰剂组的24小时UPCR分别改善了69%和70%（几何均值比=1.03; 95% CI 0.62 - 1.71; p=0.905）。与提供次优暴露的anifrolumab BR相比，anifrolumab IR的血清浓度更高。与安慰剂相比，接受阿尼福鲁单抗IR治疗的患者在数量上更多地达到CRR（45.5% vs 31.1%）、UPCR ≤0.5 mg/mg时的CRR（40.9% vs 26.7%）、非活性尿沉渣时的CRR（40.9% vs 13.3%）和糖皮质激素持续减少（55.6% vs 33.3%）。与安慰剂相比，联合阿尼夫鲁单抗的带状疱疹发生率更高（16.7% vs 8.2%）。各组严重不良事件的发生率相似。尽管未达到主要终点，但在活动性狼疮性肾炎患者中，与安慰剂相比，anifrolumab IR与终点（包括CRR）的数值改善相关。 NCT02547922。
To assess the efficacy and safety of the type I interferon receptor antibody, anifrolumab, in patients with active, biopsy-proven, Class III/IV lupus nephritis. This phase II double-blinded study randomised 147 patients (1:1:1) to receive monthly intravenous anifrolumab basic regimen (BR, 300 mg), intensified regimen (IR, 900 mg ×3, 300 mg thereafter) or placebo, alongside standard therapy (oral glucocorticoids, mycophenolate mofetil). The primary endpoint was change in baseline 24-hour urine protein–creatinine ratio (UPCR) at week (W) 52 for combined anifrolumab versus placebo groups. The secondary endpoint was complete renal response (CRR) at W52. Exploratory endpoints included more stringent CRR definitions and sustained glucocorticoid reductions (≤7.5 mg/day, W24–52). Safety was analysed descriptively. Patients received anifrolumab BR (n=45), IR (n=51), or placebo (n=49). At W52, 24-hour UPCR improved by 69% and 70% for combined anifrolumab and placebo groups, respectively (geometric mean ratio=1.03; 95% CI 0.62 to 1.71; p=0.905). Serum concentrations were higher with anifrolumab IR versus anifrolumab BR, which provided suboptimal exposure. Numerically more patients treated with anifrolumab IR vs placebo attained CRR (45.5% vs 31.1%), CRR with UPCR ≤0.5 mg/mg (40.9% vs 26.7%), CRR with inactive urinary sediment (40.9% vs 13.3%) and sustained glucocorticoid reductions (55.6% vs 33.3%). Incidence of herpes zoster was higher with combined anifrolumab vs placebo (16.7% vs 8.2%). Incidence of serious adverse events was similar across groups. Although the primary endpoint was not met, anifrolumab IR was associated with numerical improvements over placebo across endpoints, including CRR, in patients with active lupus nephritis. NCT02547922.
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