The efficacy and safety of roxadustat for the treatment of anemia in non-dialysis dependent chronic kidney disease patients: An updated systematic review and meta-analysis of randomized clinical trials

Abdelazeem, Basel; Shehata, Joseph; Abbas, Kirellos Said; El-Shahat, Nahla Ahmed; Malik, Bilal Haider; Savarapu, Pramod; Eltobgy, Mostafa; Kunadi, Arvind

doi:10.1371/journal.pone.0266243

Cited by 14 publications

(12 citation statements)

References 39 publications

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“…Roxadustat performed better efficacy in elevating hemoglobin levels than ESAs in CKD-DD patients. This result is consistent with previous meta-analyses [23][24][25]. One meta-analysis investigated roxadustat on hemoglobin in six studies [26][27][28][29][30][31].…”

Section: Comparison With Other Studiessupporting

confidence: 91%

A network meta-analysis of the efficacy of hypoxia-inducible factor prolyl-hydroxylase inhibitors in dialysis chronic kidney disease

Shou

Jin

et al. 2023

Aging

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Background: Five 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. Methods: We 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. Results: 26 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%). Conclusion: The 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.

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Section: Comparison With Other Studiessupporting

confidence: 91%

A network meta-analysis of the efficacy of hypoxia-inducible factor prolyl-hydroxylase inhibitors in dialysis chronic kidney disease

Shou

Jin

et al. 2023

Aging

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“…Although many studies have verified the effectiveness of roxadustat for renal anemia, [ 18 , 19 ] the optimal duration of treatment and dosage have not been well defined so far. As far as we know, no data are available for determining the concentration-effect relationship of roxadustat.…”

Section: Discussionmentioning

confidence: 99%

Correlation between blood concentration of roxadustat and clinical efficacy in patients with anemia of chronic kidney disease

Zhang

Zhou

2023

Medicine

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Roxadustat has been associated with the efficacy and safety in patients with chronic kidney disease-related anemia. However, the relationship between roxadustat blood concentration and clinical efficacy is lacking. To explore of the correlation between clinical efficacy and blood concentration of roxadustat in patients with renal anemia of chronic kidney diseases, so as to provide reference for rational clinical drug use. A total of 46 patients were selected with a diagnosis of renal anemia who were prescribed roxadustat at the department of nephrology of the First Hospital of Hebei Medical University from December 2019 to March 2020. The roxadustat blood concentration was determined at 12 weeks of treatment, according to the cumulative response rate, patients were divided into the response group and the nonresponse group, and the relationship between roxadustat blood concentration and treatment effect was analyzed. We also explored the correlation between various factors and the blood concentration. The patients in the response group had higher roxadustat blood concentrations than the nonresponse group ( P < .05), and there was no correlation between blood concentration and clinical characteristics such as age, gender, and dosage ( P > .05). The blood concentration of roxadustat was correlated with clinical efficacy. The higher the blood concentration, the better the clinical efficacy, meaning it might be a predictor of efficacy.

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“… 42 Conversely, hypertension has been reported by several clinical studies as one of the adverse events when roxadustat was administered for the treatment of renal anemia. 43 As sudomotor dysfunction could also result from an impaired microvascular perfusion, 44 it might be informative to monitor the blood pressure and observe the cutaneous microcirculation throughout the experiment. However, to fully explore and evaluate the therapeutic potential of the hypoxic response pathways in the progression to CRPS, further investigations are warranted.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Ischemic Conditioning with Roxadustat Does Not Affect Pain-Like Behaviors but Mitigates Sudomotor Impairment in a Murine Model of Deep Hind Paw Incision

Lu¹,

Kato²,

Toramaru³

et al. 2023

JPR

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Purpose The involvement of hypoxic response mechanisms in local functional impairments in surgical wounds is unclear. In the present study, we characterized tissue hypoxia in surgical wounds and investigated the role of pharmacological ischemic conditioning (PIC) using roxadustat, an oral prolyl hydroxylase domain enzyme inhibitor, in postoperative local functional impairments in a murine model of deep hind paw incision. Methods Male BALB/cAJcl mice aged 9–13 weeks were used in all experiments. Plantar skins of mice that underwent surgical incision were subjected to immunohistochemistry to localise tissue hypoxia. Pain-like behaviours and sudomotor function were compared between mice treated with 6-week perioperative PIC and control mice. The effects of PIC were examined in vitro by immunocytochemistry using sympathetically differentiated PC12 cells and in vivo by immunohistochemistry using plantar skins collected on postoperative day 21. Results Prominent tissue hypoxia was detected within axons in the nerve bundles underneath surgical wounds. Six-week perioperative PIC using roxadustat failed to ease spontaneous pain-like behaviors; however, it mitigated local sudomotor impairment postoperatively. Upregulation of sympathetic innervation to the eccrine glands was observed in the PIC-treated skins collected on postoperative day 21, in accordance with the in vitro study wherein roxadustat promoted neurite growth of sympathetically differentiated PC12 cells. Conclusion This study suggests that tissue hypoxia is involved in the pathogenesis of local sudomotor dysfunction associated with surgical trauma. Targeting the hypoxic response mechanisms with PIC may be of therapeutic potential in postsurgical local sympathetic impairments that can be present in complex regional pain syndrome.

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The efficacy and safety of roxadustat for the treatment of anemia in non-dialysis dependent chronic kidney disease patients: An updated systematic review and meta-analysis of randomized clinical trials

Cited by 14 publications

References 39 publications

A network meta-analysis of the efficacy of hypoxia-inducible factor prolyl-hydroxylase inhibitors in dialysis chronic kidney disease

A network meta-analysis of the efficacy of hypoxia-inducible factor prolyl-hydroxylase inhibitors in dialysis chronic kidney disease

Correlation between blood concentration of roxadustat and clinical efficacy in patients with anemia of chronic kidney disease

Pharmacological Ischemic Conditioning with Roxadustat Does Not Affect Pain-Like Behaviors but Mitigates Sudomotor Impairment in a Murine Model of Deep Hind Paw Incision

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