1.
Efficacy and safety of vadadustat compared to darbepoetin alfa on anemia in patients with chronic kidney disease: a meta-analysis
Huang Q, Liao Z, Liu X, Xia Y, Wang J
International urology and nephrology. 2022
Abstract
OBJECTIVE As a novel oral agent in treating anemia of chronic kidney disease (CKD), several clinical trials of vadadustat have been conducted to compare with darbepoetin alfa. This study systematically reviews and investigates the efficacy and safety of vadadustat in the anemia treatment with different duration in both nondialysis-dependent CKD (NDD-CKD) and dialysis-dependent CKD (DD-CKD). METHODS Several main databases were searched for randomized controlled trials (RCTs) reporting vadadustat vs darbepoetin alfa for anemia patients with CKD. The outcome indicators were focused on hemoglobin (Hb), the percentage of patients within the target Hb, the need for RBC (Red Blood Cell) transfusions, and serious adverse events (SAEs). RESULTS Four eligible studies with 8,026 participants were included. The changes of Hb levels from the baseline in the darbepoetin alfa group were significantly higher than that in the vadadustat group with DD-CKD (mean difference (MD) - 0.19, [95% confidence interval (CI), - 0.21 to - 0.17], p < 0.0001). In NDD-CKD patients, the changes of Hb levels in the two groups are not significantly different (MD = - 0.06, [95% CI, - 0.18 to 0.05], p = 0.006), especially, during the treatment duration of 20-36 weeks (MD = 0.02, [95% CI, - 0.04 to 0.08], p = 0.51). The percentage of patients within the target Hb was significantly lower in the vadadustat group than that in the darbepoetin alfa group in DD-CKD patients (MD = 0.9, [95% CI, 0.86 to 0.94], p < 0.00001), while in NDD-CKD patients, there was no significant difference (MD = 1.05, [95% CI, 0.99 to 1.12], p < 0.00001). In terms of safety, the two agents had no significant difference in the incidence of RBC transfusions and SAEs (RR = 1.26 [95% CI, 0.99 to 1.61], p = 0.52; RR = 0.97, [95% CI, 0.94 to 1.01], p = 0.19; respectively). CONCLUSION Compared to darbepoetin alfa, vadadustat had the same effect in raising the hemoglobin level in NDD-CKD patients in the short term. Vadadustat may become an effective and safe alternative for the treatment of patients with anemia and CKD, especially in NDD-CKD patients. As the application of vadadustat is still under exploration, future research should compensate for the limitations of our study to estimate the vadadustat's value.
2.
Roxadustat Treatment for Anemia in Patients Undergoing Long-Term Dialysis
Chen N, Hao C, Liu BC, Lin H, Wang C, Xing C, Liang X, Jiang G, Liu Z, Li X, et al
The New England journal of medicine. 2019
Abstract
BACKGROUND Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis and regulates iron metabolism. Additional data are needed regarding the effectiveness and safety of roxadustat as compared with standard therapy (epoetin alfa) for the treatment of anemia in patients undergoing dialysis. METHODS In a trial conducted in China, we randomly assigned (in a 2:1 ratio) patients who had been undergoing dialysis and erythropoiesis-stimulating agent therapy with epoetin alfa for at least 6 weeks to receive roxadustat or epoetin alfa three times per week for 26 weeks. Parenteral iron was withheld except as rescue therapy. The primary end point was the mean change in hemoglobin level from baseline to the average level during weeks 23 through 27. Noninferiority of roxadustat would be established if the lower boundary of the two-sided 95% confidence interval for the difference between the values in the roxadustat group and epoetin alfa group was greater than or equal to -1.0 g per deciliter. Patients in each group had doses adjusted to reach a hemoglobin level of 10.0 to 12.0 g per deciliter. Safety was assessed by analysis of adverse events and clinical laboratory values. RESULTS A total of 305 patients underwent randomization (204 in the roxadustat group and 101 in the epoetin alfa group), and 256 patients (162 and 94, respectively) completed the 26-week treatment period. The mean baseline hemoglobin level was 10.4 g per deciliter. Roxadustat led to a numerically greater mean (+/-SD) change in hemoglobin level from baseline to weeks 23 through 27 (0.7+/-1.1 g per deciliter) than epoetin alfa (0.5+/-1.0 g per deciliter) and was statistically noninferior (difference, 0.2+/-1.2 g per deciliter; 95% confidence interval [CI], -0.02 to 0.5). As compared with epoetin alfa, roxadustat increased the transferrin level (difference, 0.43 g per liter; 95% CI, 0.32 to 0.53), maintained the serum iron level (difference, 25 mug per deciliter; 95% CI, 17 to 33), and attenuated decreases in the transferrin saturation (difference, 4.2 percentage points; 95% CI, 1.5 to 6.9). At week 27, the decrease in total cholesterol was greater with roxadustat than with epoetin alfa (difference, -22 mg per deciliter; 95% CI, -29 to -16), as was the decrease in low-density lipoprotein cholesterol (difference, -18 mg per deciliter; 95% CI, -23 to -13). Roxadustat was associated with a mean reduction in hepcidin of 30.2 ng per milliliter (95% CI, -64.8 to -13.6), as compared with 2.3 ng per milliliter (95% CI, -51.6 to 6.2) in the epoetin alfa group. Hyperkalemia and upper respiratory infection occurred at a higher frequency in the roxadustat group, and hypertension occurred at a higher frequency in the epoetin alfa group. CONCLUSIONS Oral roxadustat was noninferior to parenteral epoetin alfa as therapy for anemia in Chinese patients undergoing dialysis. (Funded by FibroGen and FibroGen [China] Medical Technology Development; ClinicalTrials.gov number, NCT02652806.).
3.
Erythropoiesis-stimulating agents in the management of cancer patients with anemia: a meta-analysis
Li X, Yan Z, Kong D, Zou W, Wang J, Sun D, Jiang Y, Zheng C
Chinese Journal of Cancer Research. 2014;26((3):):268-76.
Abstract
BACKGROUND Erythropoiesis-stimulating agents (ESAs) are widely used in the management of anemia in cancer patients. Despite their apparent effectiveness, recent studies have suggested that ESAs could result in serious adverse events and even higher mortality. The aim of the current study was to evaluate the benefits and risks of ESAs in the management of cancer patients with anemia using a meta-analysis. METHODS The initial literature search covered Medline, PubMed, Embase, and the Cochrane Center Register of Controlled Trials, and identified 1,569 articles. The final meta-analysis included eight randomized controlled trials (n=2,387) in cancer patients with <11 g/dL hemoglobin (Hb) at the baseline and target Hb (for stopping ESA treatment) at no more than 13 g/dL. The assessment measures included Hb response, blood transfusion rate and adverse events that included venous thromboemblism (VTE), hypertension, and on-study mortality. The results are expressed as pooled odds ratio (OR). Publication bias was assessed using funnel plot analysis. RESULTS ESAs significantly increased the Hb concentration [OR 7.85, 95% confidence interval (CI): 5.85 to 10.53, P<0.001] and reduced the red blood cell (RBC) transfusion rate (OR 0.52, 95% CI: 0.42 to 0.65, P<0.001). ESAs did not increase the accumulated adverse events (OR 0.95, P=0.82), or the on-study mortality (OR 1.09, P=0.47). CONCLUSIONS ESAs are not associated with increased frequency of severe adverse events in anemic cancer patients when the target Hb value is no more than 13 g/dL.