Zhang Hong, Lafayette Richard, Wang Bei, Ying Lisa, Zhu Zhengying, Stone Andrew, Kristensen Jens, Barratt Jonathan
Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, China.
Division of Nephrology, Department of Medicine, Stanford University, Stanford, California.
Kidney360. 2024 Dec 1;5(12):1881-1892. doi: 10.34067/KID.0000000583. Epub 2024 Oct 9.
IgA nephropathy (IgAN), an immune-mediated kidney disease, is particularly prevalent among individuals of East Asian ancestry. Nefecon is a novel, oral, targeted-release budesonide formulation designed to inhibit galactose-deficient IgA1 formation underlying IgAN pathophysiology. We present findings in patients with IgAN from mainland China participating in the 2-year, multicenter, randomized, double-blind, phase 3 NefIgArd trial of nefecon.
Patients (aged 18 years and older) with primary IgAN (eGFR 35–90 ml/min per 1.73 m2, persistent proteinuria [urine protein–creatinine ratio ≥0.8 g/g or proteinuria ≥1 g/24 hours] despite optimized renin-angiotensin system blockade) received nefecon or placebo over 9 months, followed by a 15-month follow-up phase on supportive care alone. The primary efficacy end point was time-weighted average of eGFR over 2 years.
Sixty-two patients from mainland China were included in this prespecified analysis. The primary efficacy end point was 9.6 ml/min per 1.73 m2 (95% confidence interval, 2.0 to 19.8) in favor of nefecon versus placebo. This was consistent with (and numerically greater than) that of the global study population. Time to confirmed 30% eGFR reduction or kidney failure from baseline was substantially delayed with nefecon (patients with an event: 9%) versus placebo (30%; hazard ratio, 0.21; 95% confidence interval, 0.04 to 0.73). No deaths were reported in the China cohort. In the nefecon group, treatment-emergent serious adverse events were reported by one patient during treatment and two patients during follow-up (versus no patients and seven patients, respectively, in the placebo group). No severe infections requiring hospitalization were reported.
Nefecon treatment for 9 months showed greater preservation of eGFR over 2 years compared with placebo. The efficacy outcomes were consistent with global study results, with a numerically greater treatment benefit observed in patients from China. Nefecon was well tolerated, with no unexpected safety signals.
IgA肾病(IgAN)是一种免疫介导的肾脏疾病,在东亚血统个体中尤为普遍。耐赋康(Nefecon)是一种新型口服靶向释放布地奈德制剂,旨在抑制IgAN病理生理学中潜在的半乳糖缺陷型IgA1的形成。我们展示了来自中国大陆参与为期2年的耐赋康多中心、随机、双盲3期NefIgArd试验的IgAN患者的研究结果。
原发性IgA肾病患者(年龄18岁及以上,估算肾小球滤过率[eGFR]为35 - 90 ml/min/1.73 m²,尽管肾素 - 血管紧张素系统阻断已优化,但仍存在持续性蛋白尿[尿蛋白 - 肌酐比值≥0.8 g/g或蛋白尿≥1 g/24小时])接受耐赋康或安慰剂治疗9个月,随后仅接受支持性治疗的15个月随访期。主要疗效终点是2年内eGFR的时间加权平均值。
本预设分析纳入了62名来自中国大陆的患者。主要疗效终点显示,与安慰剂相比,耐赋康组的eGFR为9.6 ml/min/1.73 m²(95%置信区间,2.0至19.8)。这与全球研究人群的结果一致(且数值上更高)。与安慰剂组(30%;风险比,0.21;95%置信区间,0.04至0.73)相比,耐赋康组从基线确认eGFR降低30%或出现肾衰竭的时间大幅延迟(发生事件的患者:9%)。中国队列中未报告死亡病例。在耐赋康组中,1名患者在治疗期间和2名患者在随访期间报告了治疗中出现的严重不良事件(安慰剂组分别为无患者和7名患者)。未报告需要住院治疗的严重感染病例。
与安慰剂相比,耐赋康治疗9个月在2年内显示出对eGFR的更好保护。疗效结果与全球研究结果一致,在来自中国的患者中观察到数值上更大的治疗益处。耐赋康耐受性良好,未出现意外的安全信号。