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Efficacy and safety of thrombopoietin receptor agonists in children and adults with persistent and chronic immune thrombocytopenia: a meta-analysis
Li T, Liu Q, Pu T, Liu J, Zhang A
Expert opinion on pharmacotherapy. 2023;24(6):763-774
Abstract
INTRODUCTION In this paper, we systematically review the efficacy and safety of thrombopoietin receptor agonists (TPORAs) for treatment of persistent and chronic immune thrombocytopenia (ITP) in children and adults. METHODS We searched PubMed, MEDLINE, ScienceDirect, Scopus, EMbase and the Cochrane Library to collect randomized controlled trials (RCTs) of TPO-RAs which including avatrombopag hetrombopag eltrombopag and romiplostim treated persistent and chronic ITP from their earliest records to February 2022. RESULTS We included 15 RCTs with a total of 1563 patients. There were ten trials of adults and five trials of children. The results of meta-analysis showed that in adult patients, patients treated with TPO-RAs had longer duration of platelet response, higher platelet response rate, lower use of rescue therapy, and lower incidence of bleeding events, and similar incidence of adverse events compared with placebo. Except for the incidence of any bleeding, the results in children were consistent with those in adults. The network meta-analysis of data on overall platelet response rates in adults showed that avatrombopag was more effective than eltrombopag and hetrombopag. CONCLUSIONS TPO-RAs has better efficacy and higher safety in the treatment of ITP. And the overall response rate of avatrombopag in adults was higher than that in eltrombopag and hetrombopag.
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Safety and efficacy of thalidomide in patients with transfusion-dependent β-thalassemia: a randomized clinical trial
Chen JM, Zhu WJ, Liu J, Wang GZ, Chen XQ, Tan Y, Xu WW, Qu LW, Li JY, Yang HJ, et al
Signal transduction and targeted therapy. 2021;6(1):405
Abstract
Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent β-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non β0/β0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.
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A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia
Mei H, Liu X, Li Y, Zhou H, Feng Y, Gao G, Cheng P, Huang R, Yang L, Hu J, et al
Journal of hematology & oncology. 2021;14(1):37
Abstract
BACKGROUND Hetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune thrombocytopenia (ITP). This phase III study aimed to evaluate the efficacy and safety of hetrombopag in ITP patients. METHODS Patients who had not responded to or had relapsed after previous treatment were treated with an initial dosage of once-daily 2.5 or 5 mg hetrombopag (defined as the HETROM-2.5 or HETROM-5 group) or with matching placebo in a randomized, double-blind, 10-week treatment period. Patients who received placebo and completed 10 weeks of treatment switched to receive eltrombopag, and patients treated with hetrombopag in the double-blind period continued hetrombopag during the following open-label 14-week treatment. The primary endpoint was the proportion of responders (defined as those achieving a platelet count of ≥ 50 × 10(9)/L) after 8 weeks of treatment. RESULTS The primary endpoint was achieved by significantly more patients in the HETROM-2.5 (58.9%; odds ratio [OR] 25.97, 95% confidence interval [CI] 9.83-68.63; p < 0.0001) and HETROM-5 (64.3%; OR 32.81, 95% CI 12.39-86.87; p < 0.0001) group than in the Placebo group (5.9%). Hetrombopag was also superior to placebo in achieving a platelet response and in reducing the bleeding risk and use of rescue therapy throughout 8 weeks of treatment. The durable platelet response to hetrombopag was maintained throughout 24 weeks. The most common adverse events were upper respiratory tract infection (42.2%), urinary tract infection (17.1%), immune thrombocytopenic purpura (17.1%) and hematuria (15%) with 24-week hetrombopag treatment. CONCLUSIONS In ITP patients, hetrombopag is efficacious and well tolerated with a manageable safety profile. Trial registration Clinical trials.gov NCT03222843 , registered July 19, 2017, retrospectively registered.
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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.
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Effect of eltrombopag on platelet response and safety results in Chinese adults with chronic ITP - primary result of a phase III study
Yang R, Hou M, Li J, Jin J, Huang M, Yu Z, Xu X, Zhang X, Du X, Niu T, et al
Blood. 2014;124((21)): Abstract No. 1464