@article{4c1b1e184e14480f89eb131d1c89331a,
title = "JAK1/JAK2 inhibition by baricitinib in diabetic kidney disease: Results from a Phase 2 randomized controlled clinical trial",
abstract = "Background 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. Methods 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. Results 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 m 2 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. Conclusions Baricitinib decreased albuminuria in participants with Type 2 diabetes and DKD. Further research is required to determine if baricitinib reduces DKD progression.",
keywords = "JAK inhibition, albuminuria, biomarkers, diabetic nephropathy, estimated glomerular filtration rate",
author = "Tuttle, {Katherine R.} and Brosius, {Frank C.} and Adler, {Sharon G.} and Matthias Kretzler and Mehta, {Ravindra L.} and Tumlin, {James A.} and Yoshiya Tanaka and Masakazu Haneda and Jiajun Liu and Silk, {Maria E.} and Cardillo, {Tracy E.} and Duffin, {Kevin L.} and Haas, {Joseph V.} and Macias, {William L.} and Nunes, {Fabio P.} and Janes, {Jonathan M.}",
note = "Funding Information: This study was funded by Eli Lilly and Company and Incyte Corporation. Funding Information: The results presented in this manuscript have not been published previously in whole or part, except in abstract form. K.R.T. has received consulting support from Eli Lilly and Company, Boehringer-Ingelheim, Gilead and Astra Zeneca. F.C.B. III, through the University of Michigan, has received grant/research support from Eli Lilly and Company, Bristol-Myers Squibb and Takeda Pharmaceuticals. S.G.A. has received grant/research support and/or consulting fees from Eli Lilly and Company, Baxter, Bayer, Mallinckrodt, Retrophin Pharmaceuticals and Renal Research Institute. M.K., through the University of Michigan, has received grant/research support and/or consulting support from Eli Lilly and Company, Abbvie, Astra-Zeneca, Boehringer-Ingleheim, Novo-Nordisk and Pfizer. R.L.M. has received grant/research support and/or consulting support from Eli Lilly and Company, Abbvie, AM Pharma, Akebia, Ardea, Astute Inc., Baxter, CSL Behring, Ferring Research, Fresenius, Fresenius-Kabi, International Safety Adverse Events Consortium, International Society of Nephrology, Ionis, Relypsa and Regulus. J.A.T. has received grant/research support and/or consulting fees from Eli Lilly and Company, Genkyotec Pharmaceuticals, Gilead Pharmaceuticals, Jansen Pharmaceuticals and Mallinckrodt. Y.T. has received grant/research support and/or consulting fees from AbbVie, Astellas, Asahi-Kasei, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly and Company, Glaxo Smith Kline, Janssen, Kyowa-Kirin, Mitsubishi-Tanabe, MSD, Ono, Pfizer, Sanofi, Takeda, Taisho-Toyama, Teijin, YL Biologics and UCB. M.H. has received grant/research support or consulting support from Eli Lilly and Company. J.L., M.E.S., T.E.C., K.L.D., J.V.H., W.L.M., F.P.N. and J.M.J. are employees of Eli Lilly and Company and may own stock or stock options in Eli Lilly and Company. Publisher Copyright: {\textcopyright} {\textcopyright} The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA.",
year = "2018",
month = nov,
day = "1",
doi = "10.1093/ndt/gfx377",
language = "English (US)",
volume = "33",
pages = "1950--1959",
journal = "Proceedings of the European Dialysis and Transplant Association - European Renal Association. European Dialysis and Transplant Association - European Renal Association. Congress",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "11",
}