Qiyan Zheng1,2, Yahui Wang1,2, Huisheng Yang3, Luying Sun1,2, Xinwen Fu1,2, Ruojun Wei1,2, Yu Ning Liu1,2, Wei Jing Liu1,2,4. 1. Renal Research Institution of Beijing University of Chinese Medicine, Beijing, China. 2. Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China. 3. Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China. 4. Institute of Nephrology, and Zhanjiang Key Laboratory of Prevention and Management of Chronic Kidney Disease, Guangdong Medical University, Zhanjiang, China.
Abstract
Objective: Daprodustat is a novel oral agent in treating anemia of chronic kidney disease (CKD), and several clinical trials have been conducted to compare daprodustat with recombinant human erythropoietin (rhEPO) or placebo. Our systematic review aimed to investigate the efficacy and safety of daprodustat for anemia treatment in both dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients. Methods: Six databases were searched for randomized controlled trials (RCTs) reporting daprodustat vs. rhEPO or placebo for anemia patients in CKD. The outcome indicators were focused on hemoglobin (Hb), ferritin, transferrin saturation (TSAT), total iron-binding capacity (TIBC), vascular endothelial growth factor (VEGF), and serious adverse events (SAEs). Results: Eight eligible studies with 1,516 participants were included. For both NDD and DD patients, changes in Hb levels from baseline were significantly higher in daprodustat group than that in the placebo (mean difference (MD) = 1.73, [95% confidence interval (CI), 0.34 to 3.12], p = 0.01; MD = 1.88, [95% CI, 0.68 to 3.09], p = 0.002; respectively), and there was no significant difference between daprodustat and rhEPO group (MD = 0.05, [95% CI, -0.49 to 0.59], p = 0.86; MD = 0.12, [95% CI, -0.28 to 0.52], p = 0.55; respectively). The indexes of iron metabolism were improved significantly in the daprodustat group compared to placebo- or rhEPO-treated patients, while there was no similar change in terms of TSAT for DD patients. Furthermore, no trend of increasing plasma VEGF was observed in daprodustat-treated subjects. As for safety, there was no significant difference in the incidence of SAEs between daprodustat and placebo treatment, while the incidence of SAEs in the daprodustat group was significantly lower than that in the rhEPO group. Conclusion: Daprodustat was efficacious and well tolerated for anemia in both NDD and DD patients in the short term based on current RCTs. And daprodustat may become an effective alternative for treatment of anemia with CKD. Since the application of daprodustat is still under exploration, future researches should consider the limitations of our study to evaluate the value of daprodustat.
Objective: Daprodustat is a novel oral agent in treating anemia of chronic kidney disease (CKD), and several clinical trials have been conducted to compare daprodustat with recombinant humanerythropoietin (rhEPO) or placebo. Our systematic review aimed to investigate the efficacy and safety of daprodustat for anemia treatment in both dialysis-dependent (DD) and non-dialysis-dependent (NDD) patients. Methods: Six databases were searched for randomized controlled trials (RCTs) reporting daprodustat vs. rhEPO or placebo for anemiapatients in CKD. The outcome indicators were focused on hemoglobin (Hb), ferritin, transferrin saturation (TSAT), total iron-binding capacity (TIBC), vascular endothelial growth factor (VEGF), and serious adverse events (SAEs). Results: Eight eligible studies with 1,516 participants were included. For both NDD and DDpatients, changes in Hb levels from baseline were significantly higher in daprodustat group than that in the placebo (mean difference (MD) = 1.73, [95% confidence interval (CI), 0.34 to 3.12], p = 0.01; MD = 1.88, [95% CI, 0.68 to 3.09], p = 0.002; respectively), and there was no significant difference between daprodustat and rhEPO group (MD = 0.05, [95% CI, -0.49 to 0.59], p = 0.86; MD = 0.12, [95% CI, -0.28 to 0.52], p = 0.55; respectively). The indexes of iron metabolism were improved significantly in the daprodustat group compared to placebo- or rhEPO-treated patients, while there was no similar change in terms of TSAT for DDpatients. Furthermore, no trend of increasing plasma VEGF was observed in daprodustat-treated subjects. As for safety, there was no significant difference in the incidence of SAEs between daprodustat and placebo treatment, while the incidence of SAEs in the daprodustat group was significantly lower than that in the rhEPO group. Conclusion:Daprodustat was efficacious and well tolerated for anemia in both NDD and DDpatients in the short term based on current RCTs. And daprodustat may become an effective alternative for treatment of anemia with CKD. Since the application of daprodustat is still under exploration, future researches should consider the limitations of our study to evaluate the value of daprodustat.
Authors: Zhangning Fu; Xiaodong Geng; Kun Chi; Chengcheng Song; Di Wu; Chao Liu; Quan Hong Journal: Front Pharmacol Date: 2022-03-10 Impact factor: 5.810
Authors: Charli E Harlow; Josan Gandawijaya; Rosemary A Bamford; Emily-Rose Martin; Andrew R Wood; Peter J van der Most; Toshiko Tanaka; Hampton L Leonard; Amy S Etheridge; Federico Innocenti; Robin N Beaumont; Jessica Tyrrell; Mike A Nalls; Eleanor M Simonsick; Pranav S Garimella; Eric J Shiroma; Niek Verweij; Peter van der Meer; Ron T Gansevoort; Harold Snieder; Paul J Gallins; Dereje D Jima; Fred Wright; Yi-Hui Zhou; Luigi Ferrucci; Stefania Bandinelli; Dena G Hernandez; Pim van der Harst; Vickas V Patel; Dawn M Waterworth; Audrey Y Chu; Asami Oguro-Ando; Timothy M Frayling Journal: Am J Hum Genet Date: 2022-09-01 Impact factor: 11.043