-
1.
Hydroxyurea for secondary stroke prevention in children with sickle cell anaemia: a systematic review of clinical evidence and outcomes
Aderinto, N., Olatunji, G., Kokori, E., Abdulbasit, M.
Annals of medicine and surgery (2012). 2024;86(2):1042-1047
Abstract
BACKGROUND Stroke remains one of the leading complications of sickle cell anaemia (SCA) in children. Traditionally, SCA treatment focused on symptom relief. However, the high incidence of strokes in children has prompted a reevaluation of treatment, particularly hydroxyurea, for secondary stroke prevention. This study assesses hydroxyurea's effectiveness and safety in preventing secondary strokes in paediatric SCA patients. METHODS This systematic review followed a pre-defined protocol registered with PROSPERO. Comprehensive searches were conducted across PubMed, Embase, Scopus, MEDLINE, Google Scholar, and the Cochrane Library up to August 2023. Studies were included involving paediatric SCA patients at risk of secondary stroke, assessing hydroxyurea as the primary intervention. RESULTS A total of six studies meeting inclusion criteria were included. The effectiveness of hydroxyurea in preventing secondary strokes, with variable responses reported across studies. Adverse effects, including mild neutropenia, are associated with hydroxyurea treatment but with variability in reported toxicity levels. CONCLUSION Hydroxyurea holds promise in preventing recurrent strokes in children with SCA, though its efficacy and safety profiles vary among individuals. Optimal dosages and treatment durations require further investigation, necessitating vigilant monitoring of haematological parameters. Future research should refine dosing strategies, consider individual patient characteristics, assess long-term effects, and explore ancillary benefits beyond stroke prevention.
-
2.
Efficacy and safety of adeno-associated virus-based clinical gene therapy for hemophilia: A systematic review and meta-analysis
Han, Z., Yi, X., Li, J., Liao, D., Gao, G., Ai, J.
Human gene therapy. 2024
Abstract
Clinical trials of adeno-associated virus (AAV)-based gene therapy have made remarkable progress in recent years. We aimed to perform a systematic review and meta-analysis of the literature to assess the efficacy and safety of AAV-based gene therapy for hemophilia. We systematically searched the Web of Science, Embase, PubMed, and the Cochrane Database of Systematic Reviews databases, for clinical trials involving patients diagnosed with hemophilia and treated with AAV-mediated gene therapy. Data on the annualized bleeding rate (ABR), annualized infusion rate (AIR), and the incidence of treatment-related adverse events (TRAEs), severe adverse events (SAEs), and alanine aminotransferase (ALT) elevation were extracted as our outcomes. A total of 12 articles from 11 clinical trials were selected from 868 articles for meta-analysis. Pooled analyses showed that AAV-based gene therapy in hemophilia patients reduced the number of bleeding events and the number of factor infusion events by an approximate average of 7 per year and 103 per year, respectively. 80%, 18% and 63% of hemophilia patients had elevated TRAE, SAE, and ALT levels, respectively. Moreover, subgroup analysis found a significant reduction in ABR and AIR 2-3 years after the therapy. Additional findings that were not pooled including coagulation factor activity are presented in the accompanying tables. Our analysis supported the efficacy and safety of AAV-mediated gene therapy for hemophilia, providing evidence for its application as a therapeutic option for widespread clinical use in hemophilia patients in the future.
-
3.
Thrombopoietin receptor agonists use and risk of thrombotic events in patients with immune thrombocytopenic purpura: A systematic review and meta‑analysis of randomized controlled trials
Shen, N., Qiao, J., Jiang, Y., Yan, J., Wu, R., Yin, H., Zhu, S., Li, J.
Biomedical reports. 2024;20(3):44
Abstract
Thrombopoietin receptor agonists (TPO-RAs) have a role in second-line immune thrombocytopenic purpura (ITP) treatment, binding to and activating thrombopoietin receptors on megakaryocyte membranes in the bone marrow. This promotes megakaryocyte maturation and increases platelet production. Despite a 2-6% incidence of thrombotic events during TPO-RA treatment, it remains uncertain whether TPO-RAs elevate thrombosis rates. A comprehensive search of electronic databases was conducted using the relevant search criteria. To assess the risk of bias, the included studies were assessed using the revised Cochrane Risk of Bias Assessment Tool 2.0, and a meta-analysis was performed using RevMan 5.4.1. A total of 1,698 patients with ITP were included from randomized controlled trials (RCTs). There were 26 thromboembolic events in the TPO-RAs group and 4 in the control group. However, there was no significant difference in the incidence of thrombotic events between the two groups [odds ratio (OR)=1.76, 95% confidence interval (CI): 0.78-4.00, P=0.18], even if the duration of treatment was >12 weeks (OR=2.46, 95% CI: 0.81-7.43, P=0.11). Subgroup analysis showed that none of the four drugs significantly increased the incidence of thrombotic events (romiplostim: OR=0.92, 95% CI: 0.14-6.13, P=0.93; eltrombopag: OR=2.32, 95% CI: 0.64-8.47, P=0.20; avatrombopag: OR=4.15, 95% CI: 0.20-85.23, P=0.36; and hetrombopag: OR=0.76, 95% CI: 0.03-18.76, P=0.87). There was also no significant difference in the results of the double-blinded placebo-controlled RCTs (OR=1.21, 95% CI: 0.41-3.58, P=0.73). Compared to patients with ITP who did not receive TPO-RA treatment, those receiving TPO-RA treatment did not exhibit a significantly increased risk of thrombotic events.
-
4.
A systematic literature review and meta-analysis of the incidence of serious or severe hypersensitivity reactions after administration of ferric derisomaltose or ferric carboxymaltose
Kennedy, N. A., Achebe, M. M., Biggar, P., Pöhlmann, J., Pollock, R. F.
International Journal of Clinical Pharmacy. 2023
Abstract
BACKGROUND Intravenous iron is the preferred treatment for patients with iron deficiency anemia in a variety of clinical situations. Although uncommon, administration of modern IV iron formulations can result in hypersensitivity reactions (HSRs) and, rarely, anaphylactic or anaphylactoid reactions. AIM: The objective of the present study was to systematically review the literature to identify and analyze data on the incidence of HSRs after administration of ferric derisomaltose (FDI) or ferric carboxymaltose (FCM). METHOD A prospectively-registered systematic literature review was conducted to identify prospective randomized controlled trials comparing FDI and FCM with other intravenous iron formulations or oral iron. Searches were conducted in PubMed (including MEDLINE), EMBASE, and the Cochrane Library in November 2020. The relative incidence of serious or severe HSRs occurring on the day or day after dosing of intravenous iron, recorded under the standardized Medical Dictionary for Regulatory Activities query for anaphylactic reaction. RESULTS Data were obtained from seven randomized controlled trials of FCM (N = 2683) and ten of FDI (N = 3474) enrolling 10,467 patients in total. The number of patients experiencing any serious or severe HSR event was 29/2683 (1.08%) with FCM versus 5/3474 with FDI (0.14%). Bayesian inference of proportions showed the event rates to be significantly lower with FDI relative to FCM. CONCLUSION HSR events were uncommon with both intravenous iron formulations; however, the present study showed a significantly lower incidence of HSRs with FDI relative to FCM. Further large-scale, head-to-head trials of the iron formulations would be required to confirm this finding.
-
5.
Treatments of Epistaxis in Hereditary Hemorrhagic Telangiectasia: Systematic Review and Network Meta-Analysis
Chitsuthipakorn, W., Hoang, M. P., Kanjanawasee, D., Seresirikachorn, K., Snidvongs, K.
Current allergy and asthma reports. 2023
Abstract
PURPOSE OF REVIEW To analyze and compare the effects of epistaxis treatments for Hereditary Hemorrhagic Telangiectasia (HHT) patients. RECENT FINDINGS Of total of 21 randomized controlled trials (RCT), the data from 15 RCTs (697 patients, 7 treatments: timolol, propranolol, bevacizumab, doxycycline, tacrolimus, estriol/estradiol, and tranexamic acid) were pooled for the meta-analyses while the other 6 studies (treatments: electrosurgical plasma coagulation, KTP laser, postoperative packing, tamoxifen, sclerosing agent, and estriol) were reviewed qualitatively. When compared to placebo, propranolol offered the most improved epistaxis severity score, mean difference (MD), -1.68, 95% confidence interval (95%CI) [-2.80, -0.56] followed by timolol, MD -0.40, 95%CI [-0.79, -0.02]. Tranexamic acid significantly reduced the epistaxis frequency, MD -1.93, 95%CI [-3.58, -0.28]. Other treatments had indifferent effects to placebo. Qualitative analysis highlighted the benefits of tamoxifen and estriol. The adverse events of tranexamic acid, tacrolimus, propranolol, and estradiol were significantly reported. Propranolol, timolol, tranexamic acid, tamoxifen, and estriol were effective treatments which offered benefits to HHT patients in epistaxis management. Adverse events of tranexamic acid, tacrolimus, propranolol, and estradiol should be concerned.
-
6.
Efficacy of Eltrombopag with Immunosuppressive Therapy Versus Immunosuppressive Therapy Alone on Severe Aplastic Anaemia: A Systematic Review and Meta-analysis
Zhang S, Wang Q, Cui K, Cheng B, Fan J, Hu S
Clinical drug investigation. 2023
-
-
-
Free full text
-
Full text
-
Editor's Choice
Abstract
BACKGROUND AND OBJECTIVE Severe aplastic anaemia (SAA) is a syndrome of bone marrow failure caused by T cell-mediated destruction of haematopoietic stem cells and progenitor cells. Whether patients with SAA should be treated with eltrombopag (EPAG) and immunosuppressive therapy (IST) or IST alone remains debatable. Therefore, we conducted this meta-analysis to compare the efficacy of eltrombopag + IST with that of IST alone in patients with SAA and to assess the difference in the efficacy of eltrombopag in adults and children. METHODS We performed this meta-analysis by retrieving studies that met the inclusion and exclusion criteria from PubMed, EMBASE, and the Cochrane Library up to 1 January 2023. We used a random-effects model to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for primary and secondary outcomes. I(2) statistics were used to evaluate the heterogeneity of the included studies. RESULTS Six studies involving a total of 699 patients were included. In terms of the primary outcomes, our pooled results indicated that patients treated with EPAG + IST had a higher 6-month overall response rate (OR = 2.25; 95% CI, 1.60-3.16; p < 0.00001), a higher 6-month complete response rate (OR = 2.61; 95% CI, 1.82-3.74; p < 0.00001), and a lower 6-month nonresponse rate (OR = 0.32; 95% CI, 0.19-0.52; p < 0.00001). However, there was no significant difference in the rate of 6-month partial response (OR = 0.94; 95% CI, 0.49-1.81; p = 0.85). CONCLUSION This meta-analysis indicated that patients treated with additional eltrombopag for IST may have a higher rate of haematological response.
PICO Summary
Population
Children and adults with severe aplastic anaemia (6 studies, n= 699).
Intervention
Eltrombopag (EPAG) and immunosuppressive therapy (IST), (n= 364).
Comparison
IST alone (n= 335).
Outcome
Patients treated with EPAG + IST had a higher 6-month overall response rate (odds ratio (OR), 2.25; 95% confidence interval (CI), [1.60, 3.16]), a higher 6-month complete response rate (OR, 2.61; 95% CI [1.82, 3.74]), and a lower 6-month non-response rate (OR, 0.32; 95% CI [0.19, 0.52]). There was no significant difference in the rate of 6-month partial response (OR, 0.94; 95% CI [0.49, 1.81]).
-
7.
Role of thrombopoietin receptor agonists in chemotherapy-induced thrombocytopenia: A meta-analysis
Gurumurthy, G., Kisiel, F., Gurumurthy, S., Gurumurthy, J.
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2023;:10781552231219003
Abstract
INTRODUCTION Chemotherapy-induced thrombocytopenia (CIT) is a significant challenge in cancer treatment, often leading to dose reductions and reduced number of cycles. The limited effectiveness of platelet transfusions in managing CIT highlights the need for alternative treatments. Thrombopoietin receptor agonists (TPO-RA), including romiplostim, eltrombopag and avatrombopag, have shown potential in increasing platelet counts in CIT patients, necessitating a comprehensive analysis of their efficacy. METHODS This meta-analysis followed the Preferred Reporting Items for Systemic Reviews and Meta-analysis guidelines, searching Ovid databases up to 5 October 2023. The primary metric of interest was platelet count changes post-TPO-RA administration in CIT patients. RESULTS From the initial 867 studies obtained, 7 studies were selected based on the inclusion criteria. The analysis included 348 patients. A significant association was found between TPO-RA administration and platelet count increase, with a combined-effect increase of 69.52 ± 2.24 × 10(9)/l. Subgroup analysis based on Romiplostim use suggested an increase of approximately 70.11 ± 39.07 × 10(9)/l, while non-Romiplostim TPO-RAs showcased an increase of about 68.09 ± 82.58 × 10(9)/l. CONCLUSIONS The meta-analysis demonstrates the effectiveness of TPO-RAs in managing CIT. Further research comparing platelet increases across standardised TPO-RA regimens is recommended to refine treatment strategies. This analysis provides valuable insights for clinicians in tailoring CIT treatment using TPO-RAs.
-
8.
Hydroxyurea at escalated dose versus fixed low-dose hydroxyurea in adults with sickle cell disease
Ogu, U. O., Mukhopadhyay, A., Patel, K., Nelson, M. N., Strahan, K. S., Wu, L., Smeltzer, M. P., Ataga, K. I.
European journal of haematology. 2023
Abstract
Hydroxyurea reduces the frequency of vaso-occlusive complications, increases hemoglobin, and decreases mortality in sickle cell disease (SCD). Although current guidelines recommend escalation to maximum tolerated dose (MTD), the use of fixed low-dose hydroxyurea is common in low-resource countries. We conducted a systematic review and meta-analysis to evaluate the efficacy of escalated doses versus fixed low-dose of hydroxyurea in adults with SCD. Nine studies were included in the quantitative synthesis, four evaluating fixed low-dose and five evaluating escalated doses of hydroxyurea. Average daily doses of hydroxyurea in the fixed low-dose and escalated dose studies were ~10 and 22 mg/kg, respectively. There was no difference in the estimate of vaso-occlusive crisis rate between escalated and fixed low-dose studies (p = .73). The mean difference in hemoglobin from baseline to follow-up was greater for fixed low-dose than escalated dose studies (1.07 g/dL vs. 0.54 g/dL, p = .01). No difference was seen in the mean estimate of fetal hemoglobin. Despite limited eligible studies and substantial heterogeneity of effect between the studies for several outcomes, there appears to be clinical equipoise regarding the most appropriate hydroxyurea dosing regimen in adults with SCD. Controlled studies of hydroxyurea at MTD versus fixed low-dose in adults with SCD are required.
-
9.
Effectiveness of Pharmacokinetic-Guided Hydroxyurea Dose Individualization in Patients with Sickle Cell Anemia: A Mini-Review
Dos Santos Neres, J. S., Yahouédéhou, Scma, Goncalves, M. S.
Pharmaceuticals (Basel, Switzerland). 2023;16(6)
Abstract
Inconsistent therapeutic responses have been observed among patients with sickle cell anemia (SCA) undergoing hydroxyurea (HU) following the adoption of the standardized protocol. Moreover, this treatment regimen necessitates a prolonged period to reach the maximum tolerated dose in which beneficial therapeutic effects are observed in most SCA patients. To overcome this limitation, several studies have performed HU dose adjustments in SCA patients based on individualized pharmacokinetic profiles. The present systematic mini-review aims to select and analyze published data to present an overview of HU pharmacokinetics studies performed in SCA patients, as well as evaluate the effectiveness of the dose adjustment strategy. A systematic search was performed in the Embase, Pubmed, Scopus, Web of Science, Scielo, Google Scholar, and the Virtual Library of Health databases from December 2020 to August 2022, with a total of five studies included. Inclusion criteria consisted of studies in which the dose adjustment was performed in SCA patients based on pharmacokinetic parameters. Quality analyzes were performed using QAT, while data synthesis was performed according to the Cochrane Manual of Systematic Reviews of Interventions. Analysis of the selected studies revealed improved HU treatment effectiveness using personalized dosages in SCA patients. Moreover, several laboratory parameters were utilized as biomarkers of the HU response, and methods designed to simplify the adoption of this practice were presented. Despite the scarcity of studies on this topic, HU-personalized treatment based on individualized pharmacokinetic profiles represents a viable alternative for SCA patients who are candidates for HU therapy, especially for pediatric patients. Registration number: PROSPERO CRD42022344512.
-
10.
Risk of thrombotic events in immune thrombocytopenia patients treated with thrombopoietic agents: a systematic review and meta-analysis
Dong, Y., Xia, Z., Zhou, J., Hu, Y., Yue, M., Wang, Y., Hu, M.
Thrombosis journal. 2023;21(1):69
-
-
-
Free full text
-
Editor's Choice
Abstract
BACKGROUND Immune thrombocytopenia (ITP), which is a well-known hemorrhagic disorder characterized by low platelet counts, has been shown to be associated with the risk of thrombosis. Thrombopoietic agents (TAs) are extensively used as second-line treatments for ITP, effectively reducing the risk of hemorrhage. However, thrombosis, a potential adverse effect of TAs, raises clinical challenges. METHODS The MEDLINE(PubMed), Embase, and the Cochrane Library databases were systematically searched for relevant studies, including both single-arm trials and randomized controlled trials (RCTs), without language restrictions. RESULTS A total of 17 RCTs comprising 2,105 patients and 29 single-arm trials comprising 3,227 patients were included. In the single-arm meta-analysis, the pooled rate of overall thrombotic events in ITP patients receiving TAs was 2.2% (95% CI 1.0% - 3.7%). In RCTs, a higher incidence of thrombosis (33/1425 vs. 4/680) and higher risk ratios (RR) of overall, arterial, and venous thrombotic events (1.73, 95% CI [0.88, 3.39], P = 0.113; RR 1.98, 95% CI [0.80, 4.92], P = 0.141; RR 1.06, 95% CI [0.46, 2.41], P = 0.895, respectively) were observed in the TAs group than in the control group, although the differences were not significant. Subgroup analysis demonstrated that hetrombopag was the only TA with no increased thrombotic risk (rate 0.3% 95% CI [0.0 - 1.5%]; RR 0.76, 95% CI [0.03, 18.41], P = 0.864) compared to eltrombopag, avatrombopag, romiplostim, and rhTPO. Subgroup analyses also revealed that ITP patients with advanced age (3.7% vs. 1.3%, P = 0.132) or with a thrombotic history (3.0% vs. 1.4%, P = 0.257), and patients who received TAs therapy for a long duration (4.7% vs. 0.1%, P < 0.001) had an increased risk of thrombosis. CONCLUSION Our findings suggest ITP patients treated with TAs have a nonsignificantly higher risk of overall, arterial, and venous thrombotic events. Furthermore, hetrombopag is the recommended TA to avoid thrombophilia. Patients receiving long-term TAs, as well as elderly ITP patients or those with a history of thrombosis, face an increased thrombotic risk. In general, clinicians should consider potential thrombotic risks, address underlying risk factors, and ensure ongoing monitoring and follow-up when treating ITP patients with TAs.
PICO Summary
Population
Adult patients with immune thrombocytopenia (ITP), (17 randomised controlled trials (RCTs) and 29 single arm trials).
Intervention
Thrombopoietic agents (TAs) at any dosage, with or without combination therapy.
Comparison
Standard of care or placebo.
Outcome
In the single-arm meta-analysis, the pooled rate of overall thrombotic events was 2.2%; 95% CI [1.0%, 3.7%]. In RCTs, a higher incidence of thrombosis (33/1,425 vs. 4/680) and higher risk ratios (RR) of overall, arterial, and venous thrombotic events were observed in the TAs group than in the control group, although the differences were not significant. Hetrombopag was the only TA with no increased thrombotic risk compared to eltrombopag, avatrombopag, romiplostim, and recombinant human thrombopoietin (rhTPO). ITP patients with advanced age or with a thrombotic history, and patients who received TAs therapy for a long duration (4.7% vs. 0.1%) had an increased risk of thrombosis.