加拿大Aurinia制药公司Robert B Huizinga团队比较了voclosporin与安慰剂治疗狼疮性肾炎的疗效和安全性。2021年5月7日，该研究发表在《柳叶刀》杂志上。
Voclosporin是一种新型钙调神经磷酸酶抑制剂，获批用于治疗成人狼疮性肾炎，在一项2期临床试验中改善了狼疮性肾炎患者的完全肾功能缓解率。
为了评价voclosporin治疗狼疮性肾炎的疗效和安全性，研究组在27个国家的142家医院和诊所中进行了一项多中心、双盲、随机、3期临床试验。招募根据美国风湿病学会标准诊断为系统性红斑狼疮伴狼疮肾炎，2年内肾活检显示III、IV或V级（单独或合并III或IV级）的患者。将其按1：1随机分配，分别口服voclosporin或安慰剂，同时均服用霉酚酸酯和快速减量的小剂量口服类固醇。主要终点是52周时的完全肾功能缓解，定义为：尿蛋白肌酐比值小于等于0.5 mg/mg，肾功能稳定，未服用抢救性药物，连续3天及以上或在第44-52周连续7天及以上每天不超过10 mg强的松用量。
2017年4月13日至2019年10月10日，179名患者被分配到voclosporin组，178名被分配到安慰剂组。52周时，voclosporin组中有41%的患者达到完全肾功能缓解的主要终点，显著高于安慰剂组（23%）。两组各有21%的患者发生严重不良事件，发生率相似。最常见的与感染有关的严重不良事件是肺炎，两组的发生率各为4%。在研究或随访期间，共有6名患者死亡，其中voclosporin组1名，安慰剂组5名。研究人员认为导致死亡的事件均与研究治疗无关。
研究结果表明，与单独使用MMF和低剂量类固醇相比，voclosporin与MMF和低剂量类固醇联合使用在临床和统计学上具有更高的完全肾功能缓解率，且安全耐受。
附：英文原文
Title: Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial
Author: Brad H Rovin, Y K Onno Teng, Ellen M Ginzler, Cristina Arriens, Dawn J Caster, Juanita Romero-Diaz, Keisha Gibson, Joshua Kaplan, Laura Lisk, Sandra Navarra, Samir V Parikh, Simrat Randhawa, Neil Solomons, Robert B Huizinga
Issue&Volume: 2021-05-07
Abstract:
Background
Voclosporin, a novel calcineurin inhibitor approved for the treatment of adults with lupus nephritis, improved complete renal response rates in patients with lupus nephritis in a phase 2 trial. This study aimed to evaluate the efficacy and safety of voclosporin for the treatment of lupus nephritis.
Methods
This multicentre, double-blind, randomised phase 3 trial was done in 142 hospitals and clinics across 27 countries. Patients with a diagnosis of systemic lupus erythematosus with lupus nephritis according to the American College of Rheumatology criteria, and a kidney biopsy within 2 years that showed class III, IV, or V (alone or in combination with class III or IV) were eligible. Patients were randomly assigned (1:1) to oral voclosporin (23·7 mg twice daily) or placebo, on a background of mycophenolate mofetil (1 g twice daily) and rapidly tapered low-dose oral steroids, by use of an interactive web response system. The primary endpoint was complete renal response at 52 weeks defined as a composite of urine protein creatinine ratio of 0·5 mg/mg or less, stable renal function (defined as estimated glomerular filtration rate [eGFR] ≥60 mL/min/1·73 m2 or no confirmed decrease from baseline in eGFR of >20%), no administration of rescue medication, and no more than 10 mg prednisone equivalent per day for 3 or more consecutive days or for 7 or more days during weeks 44 through 52, just before the primary endpoint assessment. Safety was also assessed. Efficacy analysis was by intention-to-treat and safety analysis by randomised patients receiving at least one dose of study treatment. The trial is registered with ClinicalTrials.gov, NCT03021499.
Findings
Between April 13, 2017, and Oct 10, 2019, 179 patients were assigned to the voclosporin group and 178 to the placebo group. The primary endpoint of complete renal response at week 52 was achieved in significantly more patients in the voclosporin group than in the placebo group (73 [41%] of 179 patients vs 40 [23%] of 178 patients; odds ratio 2·65; 95% CI 1·64–4·27; p<0·0001). The adverse event profile was balanced between the two groups; serious adverse events occurred in 37 (21%) of 178 in the voclosporin group and 38 (21%) of 178 patients in the placebo group. The most frequent serious adverse event involving infection was pneumonia, occurring in 7 (4%) patients in the voclosporin group and in 8 (4%) patients in the placebo group. A total of six patients died during the study or study follow-up period (one [<1%] patient in the voclosporin group and five [3%] patients in the placebo group). None of the events leading to death were considered by the investigators to be related to the study treatments.
Interpretation
Voclosporin in combination with MMF and low-dose steroids led to a clinically and statistically superior complete renal response rate versus MMF and low-dose steroids alone, with a comparable safety profile. This finding is an important advancement in the treatment of patients with active lupus nephritis.
DOI: 10.1016/S0140-6736(21)00578-X
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00578-X/fulltext
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本期文章：《柳叶刀》：Online/在线发表
