Dataset Information

Efficacy of Different Doses of Daprodustat for Anemic Non-dialysis Patients with Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis.

ABSTRACT: (1) Background: Anemia affects about 40% of patients with chronic kidney disease (CKD). Daprodustat improves serum hemoglobin in anemic patients by inhibiting prolyl hydroxylase of hypoxia-inducible factor. We conducted a network meta-analysis to investigate the direct and indirect effects of different doses of daprodustat compared to each other and erythropoietin and placebo. (2) Methods: We searched PubMed, Cochrane Library, Web of Science, and Scopus, for randomized clinical trials (RCTs) reporting data about different doses of daprodustat for anemia in nondialysis of CKDs. (3) Results: We eventually included five RCTs with a total sample size of 4566 patients. We found that the higher the dose of daprodustat, the greater the change in serum total iron binding capacity (TIBC), hemoglobin, and ferritin from baseline. Compared to placebo, daprodustat 25-30 mg was associated with the highest significant increase in serum hemoglobin (MD = 3.27, 95% CI = [1.89; 4.65]), a decrease in serum ferritin (MD = -241.77, 95% CI = [-365.45; -118.09]) and increase in serum TIBC (MD = 18.52, 95% CI = [12.17; 24.87]). (4) Conclusion: Higher daprodustat doses were associated with a higher impact on efficacy outcomes as serum total iron-binding capacity (TIBC), hemoglobin, and ferritin. However, data about the safety profile of different doses of daprodustat is still missing.

SUBMITTER: Fadlalmola H

PROVIDER: S-EPMC9145143 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Efficacy of Different Doses of Daprodustat for Anemic Non-dialysis Patients with Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis.

Fadlalmola Hammad H Al-Sayaghi Khaled K Al-Hebshi Abdulqader A Aljohani Maher M Albalawi Mohammed M Kashari Ohoud O Alem Alaa A Alrasheedy Mariam M Balelah Saud S Almuteri Faten F Alyamani Arwa A Alwasaidi Turki T

Journal of clinical medicine 20220511 10

(1) Background: Anemia affects about 40% of patients with chronic kidney disease (CKD). Daprodustat improves serum hemoglobin in anemic patients by inhibiting prolyl hydroxylase of hypoxia-inducible factor. We conducted a network meta-analysis to investigate the direct and indirect effects of different doses of daprodustat compared to each other and erythropoietin and placebo. (2) Methods: We searched PubMed, Cochrane Library, Web of Science, and Scopus, for randomized clinical trials (RCTs) rep ...[more]

PMID: 35628849

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Project description:ImportanceDaprodustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, is being evaluated as an oral alternative to conventional erythropoiesis-stimulating agent (ESA) therapy. Few studies of anemia treatment in an incident dialysis (ID) population have been reported.ObjectiveTo evaluate the efficacy and safety of daprodustat vs darbepoetin alfa in treating anemia of chronic kidney disease in ID patients.Design, setting, and participantsThis prospective, randomized, open-label clinical trial was conducted from May 11, 2017, through September 24, 2020, in 90 centers across 14 countries. Patients with advanced CKD were eligible if they planned to start dialysis within 6 weeks from screening or had started and received hemodialysis (HD) or peritoneal dialysis (PD) within 90 days before randomization, had a screening hemoglobin (Hb) concentration of 8.0 to 10.5 g/dL (to convert to grams per liter, multiply by 10) and a randomization Hb of 8.0 to 11.0 g/dL, were ESA-naive or had received limited ESA treatment, and were iron-replete.InterventionsRandomized 1:1 to daprodustat or darbepoetin alfa.Main outcomes and measuresThe primary analysis in the intent-to-treat population evaluated the mean change in Hb concentration from baseline to evaluation period (weeks 28-52) to assess noninferiority of daprodustat vs darbepoetin alfa (noninferiority margin, -0.75 g/dL). The mean monthly intravenous (IV) iron dose from baseline to week 52 was the principal secondary end point. Rates of treatment-emergent and serious adverse events (AEs) were also compared between treatment groups to assess safety and tolerability.ResultsA total of 312 patients (median [IQR] age, 55 [45-65] years; 194 [62%] male) were randomized to either daprodustat (157 patients; median [IQR] age, 52.0 [45-63] years; 96 [61%] male) or darbepoetin alfa (155 patients; median [IQR] age, 56.0 [45-67] years; 98 [63%] male); 306 patients (98%) completed the trial. The mean (SD) Hb concentration during the evaluation period was 10.5 (1.0) g/dL for the daprodustat and 10.6 (0.9) g/dL for the darbepoetin alfa group, with an adjusted mean treatment difference of -0.10 g/dL (95% CI, -0.34 to 0.14 g/dL), indicating noninferiority. There was a reduction in mean monthly IV iron use from baseline to week 52 in both treatment groups; however, daprodustat was not superior compared with darbepoetin alfa in reducing monthly IV iron use (adjusted mean treatment difference, 19.4 mg [95% CI, -11.0 to 49.9 mg]). Adverse event rates were 76% for daprodustat vs 72% for darbepoetin alfa.Conclusions and relevanceThis randomized clinical trial found that daprodustat was noninferior to darbepoetin alfa in treating anemia of CKD and may represent a potential oral alternative to a conventional ESA in the ID population.Trial registrationClinicalTrials.gov Identifier: NCT03029208.

Project description: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.

Project description:BackgroundFive types of HIF-PHIs have been authorized for anemia treatment in CKD patients in China and Japan. These are enarodustat, roxadustat, daprodustat, vadadustat, and molidustat. How effectively they compare to ESAs about clinical results in CKD-DD patients is uncertain. This study examined the RCT evidence about the benefits and risks of HIF-PHIs and ESAs in dialysis CKD patients.MethodsWe conducted an extensive investigation and network meta-analysis of RCTs. In these RCTs, patients with CKD-DD received one of five different HIF-PHI or ESAs, a placebo, and no medical intervention. Outcomes included hemoglobin, iron parameters, and adverse events, and there were four weeks of follow-up at least. A frequentist framework for multivariate random effects meta-analyzed the results. The effect sizes of categorical variables were displayed as odds ratios. Mean differences were employed for computing continuous outcomes with common units; otherwise, standardized mean differences were applied. The Cochrane tool evaluated the bias risk in RCTs.Results26 RCTs with 14945 patients were qualified for inclusion. Compared to the placebo, HIF-PHIs and ESAs dramatically boosted hemoglobin without affecting serum iron. Roxadustat performed better hemoglobin levels than ESAs (MD 0.32, 95% CI 0.10 to 0.53) and daprodustat (0.46, 0.09 to 0.84). Roxadustat (91.8%) was the top hemoglobin treatment among all medical interventions, as determined by the SUCRA ranking. However, roxadustat caused more thrombosis and hypertension than ESAs (1.61, 1.22 to 2.12) and vadadustat (1.36, 1.01 to 1.82). The lowest rates of hypertension and thrombosis were seen in molidustat (80.7%) and ESAs (88.5%). Compared with a placebo, ESAs and HIF-PHIs all affected TSAT levels. Except for molidustat, the other four HIF-PHIs impact different iron parameters. Regarding ferritin reduction, roxadustat (90.9%) and daprodustat (60.9%) came out on top. Enarodustat (80.9%) and roxadustat (74%) placed best and second in lowering hepcidin levels. The former two medicines for TIBC improvement were vadadustat (98.7%) and enarodustat (80.9%).ConclusionThe most effective treatment for hemoglobin correction is roxadustat. The superior efficacy of reducing hepcidin makes roxadustat and enarodustat appropriate for patients with inflammation. However, the increased risk of hypertension and thrombosis associated with roxadustat should be noted. In patients at risk for hypertension and thrombosis, molidustat and ESAs may be preferable options. When administering roxadustat and daprodustat, clinicians should check ferritin to assess iron storage. Lower TSAT in patients receiving HIF-PHIs and ESAs treatment suggests intravenous iron supplements are needed.

Dataset Information

Efficacy of Different Doses of Daprodustat for Anemic Non-dialysis Patients with Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis.

Publications

Efficacy of Different Doses of Daprodustat for Anemic Non-dialysis Patients with Chronic Kidney Disease: A Systematic Review and Network Meta-Analysis.

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