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Effectiveness of shengxuexiaoban capsules combined with glucocorticoid therapy for immune thrombocytopenia: A meta-analysis
Ding MY, Li B, Yang M, Zhai WS, Song CD, Zhang J, Zhang QY, Li PF, Liu LY
PloS one. 2022;17(9):e0275122
Abstract
OBJECTIVE To evaluate the effectiveness of the Shengxuexiaoban Capsules combined with glucocorticoid therapy for immune thrombocytopenia (ITP). METHODS We collected randomized controlled trials (RCTs) using shengxuexiaoban capsules in combination with glucocorticoid to treat ITP by searching major Chinese and English electronic databases. The outcome indicators were the effective rate, recurrence rate, the number of platelets in the blood, recovery time of platelets, and adverse reactions. We used STATA 16.0 and RevMan 5.3 for meta-analysis and GRADE pro. for evidence quality evaluation. RESULTS A total of 27 RCTs were included in the meta-analysis, and the results showed a significant difference (all p<0.05) in the effective rate, recurrence rate, the number of platelets, and the recovery time of platelets (≥ 100×109) between ITP patients in the control group (who received glucocorticoid therapy alone) and test group (who received glucocorticoid therapy combined with the Shengxuexiaoban Capsules). And that Shengxuexiaoban capsules combined with glucocorticoid therapy were safe. The funnel plot and Egger's test results indicated no obvious publication bias. The GRADE evidence rating showed an intermediate quality of evidence rating for recurrence rate and overall effectiveness. CONCLUSION Glucocorticoid therapy combined with the Shengxuexiaoban Capsules showed more effectiveness in the treatment of ITP. It can improve the effective rate, reduce the recurrence rate, increase the number of platelets and shorten the recovery time of platelets, and has a good safety profile.
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A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent beta-Thalassemia
Cappellini MD, Viprakasit V, Taher AT, Georgiev P, Kuo KHM, Coates T, Voskaridou E, Liew HK, Pazgal-Kobrowski I, Forni GL, et al
N Engl J Med. 2020;382(13):1219-1231
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Editor's Choice
Abstract
BACKGROUND Patients with transfusion-dependent beta-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor beta superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients. METHODS In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent beta-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.00 to 1.25 mg per kilogram of body weight) or placebo for at least 48 weeks. The primary end point was the percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval. Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies. RESULTS A total of 224 patients were assigned to the luspatercept group and 112 to the placebo group. Luspatercept or placebo was administered for a median of approximately 64 weeks in both groups. The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%, P<0.001). During any 12-week interval, the percentage of patients who had a reduction in transfusion burden of at least 33% was greater in the luspatercept group than in the placebo group (70.5% vs. 29.5%), as was the percentage of those who had a reduction of at least 50% (40.2% vs. 6.3%). The least-squares mean difference between the groups in serum ferritin levels at week 48 was -348 mug per liter (95% confidence interval, -517 to -179) in favor of luspatercept. Adverse events of transient bone pain, arthralgia, dizziness, hypertension, and hyperuricemia were more common with luspatercept than placebo. CONCLUSIONS The percentage of patients with transfusion-dependent beta-thalassemia who had a reduction in transfusion burden was significantly greater in the luspatercept group than in the placebo group, and few adverse events led to the discontinuation of treatment. (Funded by Celgene and Acceleron Pharma; BELIEVE ClinicalTrials.gov number, NCT02604433; EudraCT number, 2015-003224-31.).
PICO Summary
Population
Adults with transfusion-dependent beta-thalassemia (n= 336).
Intervention
Luspatercept (at a dose of 1.00 to 1.25 mg per kilogram of body weight) for at least 48 weeks (n=224).
Comparison
Placebo for at least 48 weeks (n= 112).
Outcome
The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%). During any 12-week interval, the percentage of patients who had a reduction in transfusion burden of at least 33% was greater in the luspatercept group than in the placebo group, as was the percentage of those who had a reduction of at least 50%. The least-squares mean difference between the groups in serum ferritin levels at week 48 was -348 mug per liter in favor of luspatercept. Adverse events of transient bone pain, arthralgia, dizziness, hypertension, and hyperuricemia were more common with luspatercept than placebo.
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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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Eltrombopag versus romiplostim in treatment of children with persistent or chronic immune thrombocytopenia: a systematic review incorporating an indirect-comparison meta-analysis
Zhang J, Liang Y, Ai Y, Li X, Xie J, Li Y, Zheng W, He R.
Scientific Reports. 2018;8((1)):576.
Abstract
In absence of direct comparison, we conducted an indirect-comparison meta-analysis to evaluate the efficacy and safety of thrombopoietin-receptor agonists(TPO-RAs) in treatment of pediatric persistent or chronic immune thrombocytopenia(ITP). PubMed, Embase, Cochrane Library, Clinical Trials.gov, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database were searched from their earliest records to May 2017. Randomized controlled trials comparing the TPO-RAs with placebo in pediatric ITP were included. Outcomes included overall response rate(primary), durable response, overall or clinically significant bleeding, the proportion of patients receiving rescue medication, and safety. Five randomized placebo-controlled studies(N = 261) were analyzed. The overall response[Risk Ratio(RR) 0.57, 95% confidence interval(CI) 0.21-1.56], the incidence of adverse events (RR 0.96, 95%CI 0.66-1.39), durable response(RR 2.48, 95%CI 0.31-19.97), and the proportion of patients receiving rescue treatment(RR 0.73, 95%CI 0.20-2.73) were similar between eltrombopag and romiplostim group. Nevertheless, eltrombopag might have lower risk of overall bleeding(RR 0.43, 95%CI 0.23-0.80) and clinically significant bleeding(RR 0.33, 95%CI 0.12-0.89) than romiplostim. This meta-analysis suggests that eltrombopag might be similar to romiplostim in efficacy and safety, but seems to reduce the risk of bleeding compared to romiplostim. Furthermore, cost of the treatment, comorbidity of patients and drug compliance should also be considered in clinical decision making.
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Eltrombopag versus romiplostim in treatment of adult patients with immune thrombocytopenia: A systematic review incorporating an indirect-comparison meta-analysis
Zhang J, Liang Y, Ai Y, Li X, Xie J, Li Y, Zheng W, He R
Plos One. 2018;13((6)):e0198504.
Abstract
PURPOSE In absence of direct comparison randomized controlled trials (RCTs), indirect comparison was conducted to evaluate the efficacy and safety of thrombopoietin-receptor agonists (TPO-RAs) in treatment of adult immune thrombocytopenia (ITP). METHODS We searched PubMed, Embase and Cochrane Library, Clinical Trials.gov, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database from their earliest records to May 2017. RCTs comparing the TPO-RAs with placebo in adult ITP were included. Primary outcomes were the overall response rate. Secondary outcomes included safety, durable response, overall or clinically significant bleeding, and the proportion of patients receiving rescue medication. RESULTS Nine randomized placebo-controlled trials (786 participants) were included in this systematic review. Overall response [Risk Ratio(RR) = 0.59, 95%Confidence Interval(CI): 0.24-1.45], the incidence of adverse events (RR = 0.98, 95%CI: 0.79-1.21), durable response (RR = 0.47, 95%CI: 0.08-2.81), the incidence of overall bleeding (RR = 1.15, 95%CI: 0.52-2.57) and clinically significant bleeding (RR = 1.09, 95%CI: 0.37-3.24), and the proportion of patients receiving rescue treatment (RR = 0.95, 95%CI: 0.47-1.90) were similar between eltrombopag and romiplostim. CONCLUSIONS Eltrombopag and romiplostim might be equivalent in efficacy and safety for adult ITP, however, physicians should still take into account drug cost and comorbidities of the specific patient while making decisions on the treatment of ITP with TPO-RAs. REGISTRATION PROSPERO International Prospective Register of Systematic Review (PROSPERO 2017: CRD42017068661).
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Sotatercept with long-term extension for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes: a phase 2, dose-ranging trial
Komrokji R, Garcia-Manero G, Ades L, Prebet T, Steensma D P, Jurcic J G, Sekeres M A, Berdeja J, Savona M R, Beyne-Rauzy O, et al
The Lancet. Haematology. 2018;5((2):):e63-e72.
Abstract
BACKGROUND Myelodysplastic syndromes are characterised by ineffective erythropoiesis leading to anaemia. Sotatercept (ACE-011) is a novel activin receptor type IIA fusion protein that acts as a ligand trap to neutralise negative regulators of late-stage erythropoiesis. The aim of the study was to establish a safe and effective dose of sotatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes. METHODS This open-label, multicentre, dose-ranging, phase 2 trial took place at 11 treatment centres in the USA and France. Eligible patients were aged 18 years or older, had International Prognostic Scoring System-defined low-risk or intermediate-1-risk myelodysplastic syndromes, had anaemia requiring red blood cell (RBC) transfusions, and were ineligible for, or refractory to, erythropoiesis-stimulating agents (ESAs). Patients were not eligible if they had chromosome 5q deletion myelodysplastic syndromes without documented failure of lenalidomide. Patients were randomly assigned to receive either 0.1 or 0.3 mg/kg sotatercept subcutaneously, using a permuted-block method with stratification for serum erythropoietin concentration and transfusion burden. Patients were assigned to 0.5, 1.0, and 2.0 mg/kg groups in a non-randomised fashion. The primary efficacy endpoint was the proportion of patients who achieved haematological improvement-erythroid (HI-E), according to International Working Group 2006 criteria. Efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, number NCT01736683 and at EU Clinical Trials Register, number 2012-002601-22, and is ongoing. FINDINGS Between Dec 5, 2012, and July 22, 2015, 74 patients were enrolled into the study (seven to receive 0.1 mg/kg sotatercept, six to 0.3 mg/kg, 21 to 0.5 mg/kg, 35 to 1.0 mg/kg, and five to 2.0 mg/kg). 36 (49%; 95% CI 38-60) of 74 patients achieved HI-E; 29 (47%; 95% CI 35-59) of 62 patients with a high transfusion burden achieved HI-E (RBC-transfusion reduction from baseline of 4 or more units for at least 56 days), and seven (58%; 95% CI 32-81) of 12 patients with a low transfusion burden achieved HI-E (haemoglobin increase of 1.5 g/dL or more sustained for at least 56 days in the absence of transfusions). The most commonly reported adverse events were fatigue in 19 (26%) of 74 patients and peripheral oedema in 18 (24%) of 74 patients. Grade 3-4 treatment-emergent adverse events (TEAEs) were reported in 25 (34%) of 74 patients; four (5%) patients had grade 3-4 TEAEs that were considered to be treatment related. The most common grade 3-4 TEAEs were lipase increase and anaemia, which each occurred in three (4%) of 74 patients. 17 (23%) of 74 patients had at least one serious TEAE, and one patient died from a treatment-emergent subdural haematoma due to a fall. INTERPRETATION Sotatercept, a novel activin-receptor fusion protein, was well tolerated and effective for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes in whom previous ESA treatment had failed. Treatment with sotatercept could be beneficial for these patients who have few available treatment options. FUNDING Celgene Corporation.
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Thrombopoietin-receptor agonists for children with immune thrombocytopenia: a systematic review
Li Y, Zhang J, Liang Y, Ai Y, Xie J, Zheng W
Expert Opinion on Pharmacotherapy. 2017;18((15):):1543-1551
Abstract
OBJECTIVE We conducted a systematic review to assess the efficacy and safety of Thrombopoietin-receptor agonists(TPOras) for pediatric immune thrombocytopenia(ITP). METHODS We searched PubMed, Embase and Cochrane Library from their earliest records to January 2017. Randomized controlled trials(RCTs) evaluating the efficacy and safety of TPOras in children were included. Primary outcomes were durable response and clinically significant bleeding. Secondary outcomes were overall response, overall bleeding events, the proportion of patients receiving rescue medication and adverse events(AEs). RESULTS Five randomized RCTs(261participants) were included in this systematic review. Compared with placebo group, the proportion of patients achieving durable platelet response was significantly higher in Eltrombopag(92 participants, P=0.0004) or Romiplostim(62 participants, P=0.002) group, so was the overall response in Eltrombopag[RR=2.64, 95%CI(1.58, 4.44)] or Romiplostim[RR=5.05, 95%CI(2.21, 11.53)] group. Both clinically significant bleeding(159 participants, P=0.04) and total bleeding(183 participants, P=0.01) in Eltrombopag group were significantly less frequent than those in placebo group, while no significant difference between Romiplostim and placebo group. The proportion of patients receiving rescue medication, the incidence of overall AEs and serious AEs between TPO-receptor agonists and placebo group were not significantly different. CONCLUSION TPOras might improve both durable and overall platelet response in pediatric ITP, compared with placebo.