Roxadustat (FG-4592) treatment for anemia in dialysis-dependent (DD) and not dialysis-dependent (NDD) chronic kidney disease patients: A systematic review and meta-analysis

The effect of roxadustat (FG-4592) on individuals with chronic kidney diseases (CKD) patients receiving or not receiving the dialysis was unclear. The aim of this study was to evaluate the efficacy of roxadustat for the treatment of anemia in patients who are dialysis dependent (DD) or dialysis independent (NDD) CKD. We performed a systematic review of randomised controlled trials (RCTs) comparing treatment with roxadustat versus placebo or epoetin alfa up to November 2019. We investigated the efficacy of roxadustat in the levels of hemoglobin and other clinical parameters in renal anemia in patients with NDD and DD-CKD. We estimated weighted-mean difference (WMD) using random effect models. We included six RCTs comprising 1001 patients of whom 70.6 % were treated with roxadustat and 294 controls. The control group for studies of NDD-CKD patients was placebo whereas an active control of epoetin-alfa was used in studies of DD-CKD patients. Median follow-up time was 8 weeks. All trials were industry-sponsored. Overall, roxadustat increased hemoglobin levels by 1.20 g/dl (95 % CI:0.66, 1.75,P < 0.0001,I-2 = 99.3 %). Hemoglobin levels increased by 1.99 g/dl in NDD-CKD patients versus placebo and 0.52 g/dl in DD-CKD patients versus epoetin-alfa. Roxadustat was associated with a decrease the levels of hepcidin by -49.3 ng/dl (-38.5 ng/dl in NDD patients versus placebo and -27.7 ng/dl in DD patients versus epoetin alfa), a decrease in ferritin of -49.7 mu mol/l (-52.2 mu mol/l in NDD patients versus placebo and -7.3 mu mol/l in DD patients versus epoetin alfa), and increase in total iron-binding capacity of 32.2 mu mol/l (14.1 mu mol/l in NDD patients versus placebo and 13.6 mu mol/l in DD patients versus epoetin alfa). The percentage change in the transferrin saturation levels was - 2.07 % ( - 6%, NDD patients versus placebo, and + 3.7 % in DD patients versus epoetin alfa) in anemia associated CKD patients. This review found roxadustast increases the levels of hemoglobin, serum transferrin, intestinal iron absorption, and reduces hepcidin in both NDD and DD-CKD patients. Safety data is still emerging.