13 Jun JAK1-2 inhibitor Baricitinib May Limit Progression of Diabetic Kidney Disease
MedicalResearch.com Interview with:
Frank C. Brosius, MD
Professor, Internal Medicine and Physiology
Chief, Division of Nephrology
University of Michigan Ann Arbor, MI
Dr. Matthias Kretzler MD
Professor, Internal Medicine
Research Professor, Computational Medicine and Biology
University of Michigan Ann Arbor, MI
Katherine R. Tuttle MD
Clinical Professor of Medicine, Division of Nephrology
Medical & Scientific Director, Providence Medical Research Center/Sacred Heart Center
Professor of Basic Medical Sciences, WWAMI Program
Washington State University
Medical Research: What is the background for this study?
Response: Our University of Michigan team had found that JAK-STAT gene expression was increased in kidneys in patients with diabetic kidney disease and that these changes correlated with progression of kidney disease. We subsequently substantiated these changes in other studies and have found that by increasing expression of just one of these genes, JAK2, in a single kidney cell type (podocytes) in mice that we can make their diabetic kidney disease much worse.
At around the same time, investigators at Eli Lilly and Co. had FDA approval to test a JAK1-2 inhibitor, baricitinib, in patients with rheumatoid arthritis. The Lilly scientists saw our human results and thought about using baricitinib in patients with diabetic kidney disease. After initial discussions with Dr. Kretzler and myself they concluded that there was good reason to move ahead with this study and just 14 months after the initial meeting the phase 2 clinical trial of baricitinib in the treatment of patients with diabetic kidney disease was initiated.
Medical Research: What are the main findings? What should clinicians and patients take away from your report?
Response: This is an initial report and so there will need to be further testing of the effectiveness and safety of baricitinib before it is a new treatment to prevent progression of diabetic kidney disease. However, the results are very encouraging. The drug reduced abnormal losses of protein in the urine, a marker of kidney injury, by about 40 percent. Furthermore, it reduced levels of compounds in the blood and urine that are markers of inflammation in the kidneys and elsewhere in the body. This result strongly suggests that baricitinib is tamping down the inflammation that is very important in causing progressive kidney injury in diabetes. There were no major side effects except a modest and expected reduction in the hemoglobin in patients on the highest dose of baricitinib.
Medical Research: What recommendations do you have for future research as a result of this study?
Response: Discussions are ongoing about next steps, but we are very hopeful that Lilly will move ahead with further definitive trials of baricitinib in diabetic kidney disease. Positive results in bigger and longer trials could set the stage for FDA approval of baricitinib in the treatment of the millions of patients worldwide that have this disease. We hope that other investigators look carefully at the JAK-STAT pathway to determine its role in other kidney diseases and to potentially find other methods to inhibit this pathway to increase the likelihood of finding new, safe and effective agents for all individuals with chronic kidney disease.
Citation: Presented at American Diabetes Association June 2015
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MedicalResearch.com Interview with: Frank C. Brosius, MD Professor, Internal Medicine and Physiology, Chief, Division of Nephrology, & University of Michigan Ann Arbor, MI (2015). JAK1-2 inhibitor Baricitinib May Limit Progression of Diabetic Kidney Disease
Last Updated on June 13, 2015 by Marie Benz MD FAAD