Efficacy and Safety of Daprodustat Vs rhEPO for Anemia in Patients With Chronic Kidney Disease: A Meta-Analysis and Trial Sequential Analysis
Frontiers in pharmacology. 2022;13:746265
Introduction: Daprodustat, a novel hypoxia-inducible factor prolyl-hydroxylase inhibitor (HIF-PHI), its efficacy and safety remain unclear. Thus, we conducted this meta-analysis aiming at investigating its efficacy and safety on the treatment of patients with chronic kidney disease (CKD)-related anemia. Methods: We systematically searched for relevant studies in PubMed, Embase, Cochrane Library and Clinical Trial Registries databases from inception until December 2021. We selected randomized controlled trials comparing daprodustat with recombinant human erythropoietin (rhEPO) in anemia patients with CKD with or without dialysis. Results: Seven studies including 7933 patients met the inclusion criteria. For both nondialysis-dependent (NDD-) CKD and dialysis-dependent (DD-) CKD patients, the pooled results showed that there was no significant difference in the changes in hemoglobin levels between the daprodustat and rhEPO groups (mean difference (MD) = -0.01, 95% confidence interval (CI) = -0.38, 0.35, p = 0.95; MD = 0.15, 95% CI = -0.29, 0.60, p = 0.50; respectively). In addition, a significant increase in transferrin saturation (TSAT), total iron binding capacity (TIBC) and total iron was observed in daprodustat groups compared with rhEPO groups in DD-CKD patients (p < 0.05). As for safety, the overall frequency of adverse events was similar between the daprodustat and rhEPO groups in DD-CKD patients (relative risk (RR) = 0.99, 95%CI = 0.92, 1.06, p = 0.76), and the trial sequential analysis (TSA) confirmed this result. But for NDD-CKD patients, the incidence of adverse events in the daprodustat groups was significantly higher than that of rhEPO groups (RR = 1.04, 95%CI = 1.01,1.07, p = 0.02), while the TSA corrected this result. No trend of increasing incidence of serious adverse events was found in all daprodustat treated patients, but the TSA could not confirm this result. Conclusion: Although daprodustat was noninferior to rhEPO in correcting anemia in both NDD-CKD and DD-CKD patients, it seemed to have a better effect on optimizing iron metabolism in DD-CKD patients. Daprodustat may be a promising alternative for the treatment of anemia in patients with CKD. However, due to the lack of included studies, future researches are needed to further evaluate the therapeutic effect of daprodustat. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021229636.
Antiviral agents, glucocorticoids, antibiotics, and intravenous immunoglobulin usage in 1142 patients with coronavirus disease 2019: a systematic review and meta-analysis
Pol Arch Intern Med. 2020
INTRODUCTION Treatment effects of antiviral agents, glucocorticoids, antibiotics, and intravenous immunoglobulin are controversial in patients with Coronavirus disease 2019 (COVID-19). OBJECTIVES To evaluate the impact of drug therapy on the risk of death in patients with COVID-19. PATIENTS AND METHODS The PubMed, EMBASE, Web of Science, Cochrane Library, and major preprint platforms were searched to retrieve articles till 7 April 2020. The effects of specific drug interventions on mortality were assessed in COVID-19 patients. Odds ratios (ORs) and Risk Ratios (RRs) with corresponding 95% confidence intervals (CIs) were pooled using random-effects models. RESULTS Of 3421 references, six studies were included. Pooled results from retrospective studies revealed that antiviral agents may contribute to survival benefit (OR, 0.42, 95% CI, 0.17-0.99, p=0.048, I2=82.8%), while the RCT found no effects of antiviral agent on mortality (RR 0.77, 95% CI, 0.45-1.30, p=0.33). Glucocorticoids usage leads to an increased risk of death (OR 2.43, 95% CI, 1.44-4.10, p=0.001, I2=61.9%). Antibiotics intervention did not significantly affect mortality (OR 1.13, 95% CI, 0.67-1.89, p=0.64, I2=0%). Likewise, intravenous immunoglobulin had non-significant effects on mortality (OR 2.66, 95% CI, 0.72-9.89, p=0.14, I2=93.1%). CONCLUSIONS With the varied heterogeneities across interventions, the current evidence indicated a probable survival benefit of antiviral agent usage and a harmful effect of glucocorticoids in patients with COVID-19. None of antibiotics or intravenous immunoglobulin usage was associated with survival benefit in patients with COVID-19.