Providence Health Care, Spokane, WA, USA.
The Kidney Research Institute, Division of Nephrology, University of Washington School of Medicine, Seattle, WA, USA.
Nephrol Dial Transplant. 2018 Nov 1;33(11):1950-1959. doi: 10.1093/ndt/gfx377.
Inflammation signaled by Janus kinases (JAKs) promotes progression of diabetic kidney disease (DKD). Baricitinib is an oral, reversible, selective inhibitor of JAK1 and JAK2. This study tested the efficacy of baricitinib versus placebo on albuminuria in adults with Type 2 diabetes at high risk for progressive DKD.
In this Phase 2, double-blind, dose-ranging study, participants were randomized 1:1:1:1:1 to receive placebo or baricitinib (0.75 mg daily; 0.75 mg twice daily; 1.5 mg daily; or 4 mg daily), for 24 weeks followed by 4-8 weeks of washout.
Participants (N = 129) were 63±9.1 (mean±standard deviation) years of age, 27.1% (35/129) women and 11.6% (15/129) African-American race. Baseline hemoglobin A1c (HbA1c) was 7.3±1% and estimated glomerular filtration rate was 45.0±12.1 mL/min/1.73 m2 with first morning urine albumin-creatinine ratio (UACR) of 820 (407-1632) (median; interquartile range) mg/g. Baricitinib, 4 mg daily, decreased morning UACR by 41% at Week 24 compared with placebo (ratio to baseline 0.59, 95% confidence interval 0.38-0.93, P = 0.022). UACR was decreased at Weeks 12 and 24 and after 4-8 weeks of washout. Baricitinib 4 mg decreased inflammatory biomarkers over 24 weeks (urine C-X-C motif chemokine 10 and urine C-C motif ligand 2, plasma soluble tumor necrosis factor receptors 1 and 2, intercellular adhesion molecule 1 and serum amyloid A). The only adverse event rate that differed between groups was anemia at 32.0% (8/25) for baricitinib 4 mg daily versus 3.7% (1/27) for placebo.
Baricitinib decreased albuminuria in participants with Type 2 diabetes and DKD. Further research is required to determine if baricitinib reduces DKD progression.
Janus 激酶（JAK）介导的炎症促进了糖尿病肾病（DKD）的进展。巴瑞替尼是一种口服、可逆、选择性 JAK1 和 JAK2 抑制剂。这项研究旨在测试巴瑞替尼与安慰剂在 2 型糖尿病高危进展性 DKD 成人中的白蛋白尿疗效。
这是一项 2 期、双盲、剂量范围研究，参与者按照 1:1:1:1:1 的比例随机分为安慰剂组或巴瑞替尼组（0.75mg 每日一次；0.75mg 每日两次；1.5mg 每日一次；4mg 每日一次），治疗 24 周，随后进行 4-8 周的洗脱期。
共有 129 名参与者（N=129）年龄为 63±9.1（均数±标准差）岁，27.1%（35/129）为女性，11.6%（15/129）为非裔美国人。基线糖化血红蛋白（HbA1c）为 7.3±1%，肾小球滤过率估计值为 45.0±12.1ml/min/1.73m2，晨尿白蛋白/肌酐比值（UACR）为 820（407-1632）（中位数；四分位距）mg/g。与安慰剂相比，巴瑞替尼 4mg 每日一次可使第 24 周早晨 UACR 降低 41%（与基线相比比值为 0.59，95%置信区间 0.38-0.93，P=0.022）。UACR 在第 12 周和第 24 周以及洗脱期 4-8 周后均下降。巴瑞替尼在 24 周内降低了炎症生物标志物（尿 CXCL10 和尿 CCL2，血浆可溶性肿瘤坏死因子受体 1 和 2，细胞间黏附分子 1 和血清淀粉样蛋白 A）。唯一组间不良反应发生率不同的是贫血，巴瑞替尼 4mg 每日一次组为 32.0%（8/25），安慰剂组为 3.7%（1/27）。
巴瑞替尼降低了 2 型糖尿病和 DKD 患者的白蛋白尿。还需要进一步的研究来确定巴瑞替尼是否可以降低 DKD 的进展。
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