1.
Roxadustat for the treatment of anemia in patients with chronic kidney diseases: a meta-analysis
Zhang L, Hou J, Li J, Su SS, Xue S
Aging. 2021;13
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Editor's Choice
Abstract
BACKGROUND Anemia is a common complication of chronic kidney disease (CKD). Treating renal anemia with erythropoiesis-stimulating agents (ESAs) or erythropoietin analogs is effective but has side effects. Therefore, we performed a meta-analysis to assess the efficacy and safety of roxadustat in treating CKD-induced anemia. METHODS We searched publications online and conducted a meta-analysis and calculated relative risks with 95% confidence intervals (CIs) for dichotomous data and mean differences (MD) with 95% CIs for continuous data. RESULTS Of 110 articles, nine were included that contained 12 data sets and 11 randomized control trials on roxadustat. In the non-dialysis-dependent (NDD) high-dose/low-dose subgroups, the change in hemoglobin (Hb) levels was significantly higher in the roxadustat group than in the placebo group (P<0.0001, P=0.001, respectively). The Hb response rate of the roxadustat is higher in the NDD subgroup than in the placebo group (P<0.00001, MD=6.92, 95% CI: 4.03, 11.89). However, in the dialysis-dependent subgroup, there was no significant difference in the change in Hb levels or the Hb response rate between the roxadustat and ESA groups. There was no change in the mortality in the roxadustat group compared to that in the placebo/ESA group. Hyperkalemia may be a side effect of roxadustat. CONCLUSIONS Roxadustat elevated the serum Hb levels in a manner similar to that observed for ESAs. Roxadustat raised the Hb levels more significantly than the placebo and showed a higher Hb response rate than the placebo group in NDD patients. Roxadustat is a safe and effective drug for anemia in CKD patients.
PICO Summary
Population
Patients with chronic kidney disease-induced anaemia (9 studies).
Intervention
Roxadustat.
Comparison
Erythropoiesis-stimulating agents (ESAs) or erythropoietin analogues or placebo.
Outcome
In the non-dialysis-dependent (NDD) high-dose/low-dose subgroups, the change in haemoglobin (Hb) levels was significantly higher in the roxadustat group than in the placebo group. The Hb response rate of the roxadustat is higher in the NDD subgroup than in the placebo group (MD=6.92). In the dialysis-dependent subgroup, there was no significant difference in the change in Hb levels or the Hb response rate between the roxadustat and ESA groups. There was no change in the mortality in the roxadustat group compared to that in the placebo/ESA group.
2.
Iron Chelation in Transfusion-Dependent Patients With Low- to Intermediate-1-Risk Myelodysplastic Syndromes: A Randomized Trial
Angelucci E, Li J, Greenberg P, Wu D, Hou M, Montano Figueroa EH, Rodriguez MG, Dong X, Ghosh J, Izquierdo M, et al
Ann Intern Med. 2020
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Editor's Choice
Abstract
Background: Iron chelation therapy (ICT) in patients with lower-risk myelodysplastic syndromes (MDS) has not been evaluated in randomized studies. Objective: To evaluate event-free survival (EFS) and safety of ICT in iron-overloaded patients with low- or intermediate-1-risk MDS. Design: Multicenter, randomized, double-blind, placebo-controlled trial (TELESTO). (ClinicalTrials.gov: NCT00940602). Setting: 60 centers in 16 countries. Participants: 225 patients with serum ferritin levels greater than 2247 pmol/L; prior receipt of 15 to 75 packed red blood cell units; and no severe cardiac, liver, or renal abnormalities. Intervention: Deferasirox dispersible tablets (10 to 40 mg/kg per day) (n = 149) or matching placebo (n = 76). Measurements: The primary end point was EFS, defined as time from date of randomization to first documented nonfatal event (related to cardiac or liver dysfunction and transformation to acute myeloid leukemia) or death, whichever occurred first. Results: Median time on treatment was 1.6 years (interquartile range [IQR], 0.5 to 3.1 years) in the deferasirox group and 1.0 year (IQR, 0.6 to 2.0 years) in the placebo group. Median EFS was prolonged by approximately 1 year with deferasirox versus placebo (3.9 years [95% CI, 3.2 to 4.3 years] vs. 3.0 years [CI, 2.2 to 3.7 years], respectively; hazard ratio, 0.64 [CI, 0.42 to 0.96]). Adverse events occurred in 97.3% of deferasirox recipients and 90.8% of placebo recipients. Exposure-adjusted incidence rates of adverse events (≥15 events per 100 patient treatment-years) in deferasirox versus placebo recipients, respectively, were 24.7 versus 23.9 for diarrhea, 21.8 versus 18.7 for pyrexia, 16.7 versus 22.7 for upper respiratory tract infection, and 15.9 versus 0.9 for increased serum creatinine concentration. Limitations: The protocol was amended from a phase 3 to a phase 2 study, with a reduced target sample size from 630 to 210 participants. There was differential follow-up between treatment groups. Conclusion: The findings support ICT in iron-overloaded patients with low- to intermediate-1-risk MDS, with longer EFS compared with placebo and a clinically manageable safety profile. Therefore, ICT may be considered in these patients. Primary Funding Source: Novartis Pharma AG.
PICO Summary
Population
Iron-overloaded patients with low- or intermediate-1-risk myelodysplastic syndromes (MDS), (n= 225).
Intervention
Deferasirox dispersible tablets (10 to 40 mg/kg per day), (n= 149).
Comparison
Matching placebo (n = 76).
Outcome
Median time on treatment was 1.6 years in the deferasirox group and 1.0 year in the placebo group. Median EFS was prolonged by approximately 1 year with deferasirox versus placebo (3.9 years vs. 3.0 years, respectively; hazard ratio, 0.64. Adverse events occurred in 97.3% of deferasirox recipients and 90.8% of placebo recipients. Exposure-adjusted incidence rates of adverse events (>/=15 events per 100 patient treatment-years) in deferasirox versus placebo recipients, respectively, were 24.7 versus 23.9 for diarrhea, 21.8 versus 18.7 for pyrexia, 16.7 versus 22.7 for upper respiratory tract infection, and 15.9 versus 0.9 for increased serum creatinine concentration.
3.
Efficacy and safety of iron chelator for transfusion-dependent patients with myelodysplastic syndrome: a meta-analysis
Zhang J, Shi P, Liu J, Li J, Cao Y
Hematology (Amsterdam, Netherlands). 2019;24(1):669-678
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Editor's Choice
Abstract
To systematically evaluate the efficacy and safety of iron chelators for transfusion-dependent patients with MDS. Thirteen cohort studies with 12,990 patients diagnosed with MDS were included in this study. According to m eta-analysis results transfusion-dependent MDS patients with secondary iron overload had a longer (HR = 0.52, 95%CI = 0.43-0.62, P < 0.001). Further subgroup analysis revealed a longer LFS (HR = 0.84, 95%CI = 0.76-0.93, P = 0.001) in MDS patients receiving iron chelators than in MDS patients not receiving iron chelators (HR = 0.52, 95%CI = 0.43-0.62, P < 0.001) and in patients with lower-risk MDS (HR = 0.50, 95%CI = 0.43-0.59, P < 0.001). Subgroup analysis of DFX showed that compared with patients not treated with iron chelators, the group receiving DFX monotherapy had significantly increased OS (HR = 0.43, 95%CI = 0.27-0.69, P < 0.001). In terms of tolerance, meta-analysis of binary variables in CAEs indicated that the occurrence of CAEs was significantly reduced by ICT (RR = 0.64, 95%CI = 0.57-0.71, P < 0.001).
PICO Summary
Population
Transfusion dependent patients with myelodysplastic syndrome (n=12,990, 13 studies).
Intervention
Iron chelator therapy (n=1999).
Comparison
No iron chelator therapy (n=10991).
Outcome
Patients with secondary iron overload had a longer overall survival. Further subgroup analysis revealed a longer leukaemia free survival (LFS) in MDS patients receiving iron chelators than in MDS patients not receiving iron chelators and in patients with lower-risk MDS. Subgroup analysis of Deferasirox (DFX) showed that compared with patients not treated with iron chelators, the group receiving DFX monotherapy had significantly increased overall survival. The occurrence of cardiac adverse eventss was significantly reduced by iron chelator therapy.