Efficacy and Safety of Avatrombopag in Patients with Chronic Immune Thrombocytopenia: A Systematic Literature Review and Network Meta-Analysis
Advances in therapy. 2021
INTRODUCTION A network meta-analysis (NMA) was performed to assess the efficacy and safety of avatrombopag, relative to eltrombopag, romiplostim, and fostamatinib, for patients with chronic immune thrombocytopenia (ITP) not responding adequately to corticosteroids. METHODS A systematic search of publication and clinical trial databases was conducted to identify relevant randomized controlled trials (RCTs) and observational studies. Data from eligible studies were extracted and analyzed in a Bayesian framework using relative effect sizes vs placebo. Outcomes included durable platelet response; need for rescue therapy; reduction in use of concomitant ITP medication; incidence of any or World Health Organization (WHO) grade 2-4 bleeding events, and any adverse events. Results were reported as odds ratios or incidence rate ratios (IRR) with 95% credible intervals (CrIs). RESULTS The NMA included seven phase 3 RCTs. Compared with placebo, avatrombopag was associated with statistically significant improvements in durable platelet response, reduction in use of concomitant ITP medication, and incidence of any bleeding events. Statistically significant differences vs placebo were also observed for durable platelet response and need for rescue therapy (eltrombopag, romiplostim, and fostamatinib); reduction in use of concomitant ITP medication (eltrombopag and romiplostim); incidence of any bleeding events (fostamatinib); and incidence of WHO grade 2-4 bleeding events (romiplostim and fostamatinib). No statistically significant differences were observed for any adverse events. Avatrombopag was associated with a statistically significant lower incidence of any bleeding events vs eltrombopag (IRR 0.38 [95% CrI 0.19, 0.75]) and romiplostim (IRR 0.38 [95% Crl 0.17, 0.86]); no other between-treatment differences were observed. CONCLUSION In this NMA, avatrombopag significantly increased the chance of achieving durable platelet response and reducing the use of concomitant ITP medication vs placebo, and significantly reduced the incidence of any bleeding events compared with placebo, eltrombopag, and romiplostim. The study aims to help guide clinicians managing patients with chronic ITP and insufficient response to previous treatment.
Patients with chronic immune thrombocytopenia (ITP), not responding to corticosteroids (7 studies).
Eltrombopag, romiplostim, fostamatinib therapy or placebo.
Compared with placebo, avatrombopag was associated with statistically significant improvements in durable platelet response, reduction in use of concomitant ITP medication, and incidence of any bleeding events. Statistically significant differences vs. placebo were also observed for durable platelet response and need for rescue therapy (eltrombopag, romiplostim, and fostamatinib); reduction in use of concomitant ITP medication (eltrombopag and romiplostim); incidence of any bleeding events (fostamatinib); and incidence of WHO grade 2-4 bleeding events (romiplostim and fostamatinib). No statistically significant differences were observed for any adverse events. Avatrombopag was associated with a statistically significant lower incidence of any bleeding events vs. eltrombopag (IRR 0.38) and romiplostim (IRR 0.38); no other between-treatment differences were observed.
Effect of blood donor characteristics on transfusion outcomes: a systematic review and meta-analysis
Transfusion Medicine Reviews. 2016;30((2):):69-80
Optimal selection of blood donors is critical for ensuring the safety of blood products. The current selection process is concerned principally with the safety of the blood donor at the time of donation and of the recipient at the time of transfusion. Recent evidence suggests that the characteristics of the donor may affect short- and long-term transfusion outcomes for the transfused recipient. We conducted a systematic review with the primary objective of assessing the association between blood donor characteristics and red blood cell (RBC) transfusion outcomes. We searched MEDLINE, EMBASE, and Cochrane Central databases and performed manual searches of top transfusion journals for all available prospective and retrospective studies. We described study characteristics, methodological quality, and risk of bias and provided study-level effect estimates and, when appropriate, pooled estimates with 95% confidence intervals using the Mantel-Haenszel or inverse variance approach. The overall quality of the evidence was graded using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. From 6121 citations identified by our literature search, 59 studies met our eligibility criteria (50 observational, 9 interventional). We identified the evaluation of association of 17 donor characteristics on RBC transfusion outcome. The risk of bias and confounding of the included studies was high. The quality of evidence was graded as very low to low for all 17 donor characteristics. Potential associations were observed for donor sex with reduced survival at 90 days and 6 months in male recipients that receive donated blood from females (hazard ratio 2.60 [1.09, 6.20] and hazard ratio 2.40 [1.10, 5.24], respectively; n = 1), Human Leukocyte Antigen - antigen D Related (HLA-DR) selected transfusions (odds ratio [OR] 0.39 [0.15, 0.99] for the risk of transplant alloimmunization, n = 9), presence of antileukocyte antibodies (OR 5.84 [1.66, 20.59] for risk of transfusion-related acute lung injury, n = 4), and donor RBC antigens selection (OR 0.20 [0.08, 0.52] for risk of alloimmunization, n = 4). Based on poor quality evidence, positive antileukocyte antibodies, female donor to male recipients, HLA-DR selected RBC transfusion, or donor RBC antigen selection may affect RBC transfusion outcome. Our findings that donor characteristics may be associated with transfusion outcomes warrant establishing vein-to-vein data infrastructure to allow for large robust evaluations. PROSPERO registration number: CRD42013006726.
Effect of blood donor characteristics on transfusion outcomes: a systematic review and meta-analysis
Transfusion. 2015;55((Suppl. 3)):123A.. Abstract no.SP176.
Effect of blood donor characteristics on transfusion outcomes: a protocol for systematic review and meta-analysis
Systems Review. 2014;3((1):):28.
BACKGROUND Optimal selection of blood donors is of paramount importance in ensuring the safety of blood products. The current selection process is concerned principally with the safety of the blood donor and the safety of the patient that receives the blood. Recent evidence suggests that the characteristics of the donor may affect transfusion outcomes for the recipient. METHODS We will conduct a systematic review of the association between major blood donor characteristics and red blood cell (RBC) transfusion outcomes. The primary objective is to assess the association of blood donor characteristics and the risk of adverse short-term and long-term clinical outcomes after RBC transfusion. We will search MEDLINE, EMBASE, Cochrane Central databases, as well as perform manual searches of top transfusion medical journals for prospective and retrospective studies. Study characteristics will be reported and the methodological quality of studies will be assessed. When appropriate, we will provide pooled odds ratio with 95% confidence intervals of the effect estimates, study clinical heterogeneity using pre-defined sensitivity and subgroup analyses, and study statistical heterogeneity using the I2 test. DISCUSSION The results of this systematic review will provide an evidence base regarding the potential clinical effects of donor characteristics on transfusion recipients to better guide policy and clinical practice. The evidence gathered from this review will also identify strengths and weaknesses of published studies regarding donor characteristics and transfusion outcomes and will identify knowledge gaps to inform future research in this field of transfusion medicine. TRIAL REGISTRATION PROSPERO Registration Number: CRD42013006726.
ABO-identical vs. non-identical platelet transfusion. A systematic review
BACKGROUND The significance of ABO matching for platelet (PLT) transfusion has not been clearly defined. The primary objective of this report is to assess whether ABO-identical PLT transfusion is associated with improved mortality and/or morbidity for patients with hematologic/oncologic disorders. STUDY DESIGN AND METHODS A systematic review to January 2009 was conducted. Data on mortality, morbidity, PLT refractoriness, and PLT increment after transfusion were abstracted. RESULTS A total of 100 citations were identified. Nineteen studies were included in the systematic review. A total of 1502 patients from three randomized controlled trials and 16 observational studies were included. Survival, bleeding events, and transfusion reactions were only considered as secondary outcomes in the reports reviewed. The PLT count increment was the primary outcome of several studies and was consistently higher with ABO-identical PLT transfusion. The largest difference in increment between ABO-identical and nonidentical PLT transfusion was 4 x 10(9)/L. No consistent benefit in clinical outcomes was noted. Survival was assessed in three reports with conflicting results. Although two studies described bleeding as an outcome, the assessment of hemorrhage was considered inadequate. In six studies, ABO-nonidentical PLT transfusion was not associated with transfusion reactions, and the results from four studies addressing the impact of ABO-identical PLT transfusion on PLT and red blood cell utilization were conflicting. CONCLUSION ABO-identical PLT transfusion results in a higher PLT increment. Randomized controlled trials are required to definitely determine the effect of ABO-identical PLT transfusion on survival, bleeding events, or transfusion reactions.
In vivo evaluation of AMICUS platelets in additive solution
Transfusion. 2008;48((S2):):11A-12A.. Abstract No. S26-020C.
Six Sigma study to reduce quantity not sufficient (QNS) rates on mobile blood drives
Transfusion. 2006;46((9s):):192-3A.. Abstract No. AP64.
Use of intravenous immunoglobulin for treatment of neurologic conditions: a systematic review
BACKGROUND Given the increasing use of intravenous immunoglobulin (IVIG) for various neurologic conditions and uncertainty pertaining to its benefits and harms, a systematic review was conducted of randomized controlled trials (RCTs) evaluating IVIG for all neurologic indications for which there was at least one published trial. STUDY DESIGN AND METHODS For this systematic review, a systematic search strategy was applied to MEDLINE (1966-June 2003) and the Cochrane Register of Controlled Trials (June 2003) to identify potentially eligible RCTs comparing IVIG to placebo or an active control. All dosage regimens were considered. Abstracts were excluded, and no restriction was placed on language of publication. Two investigators independently performed data extraction with a standardized form. Measures of effect were calculated for each trial independently, and studies were pooled based on clinical and methodologic judgment as to its appropriateness. Where pooling of trials was inappropriate, a qualitative discussion of findings is provided. RESULTS AND CONCLUSIONS Thirty-seven trials representing 14 conditions were identified. IVIG is more effective than placebo for treatment of relapsing-remitting multiple sclerosis and idiopathic chronic inflammatory demyelinating polyneuropathy. There is also potential benefit for treatment of multifocal motor neuropathy, myasthenia gravis, dermatomyositis, stiff-person syndrome, and Lambert-Eaton myasthenic syndrome. There was insufficient evidence to determine whether IVIG therapy was more effective than plasma exchange for Guillain-Barré syndrome. There was also insufficient evidence regarding paraprotein-associated polyneuropathy. No evidence of benefit was observed for secondary progressive multiple sclerosis or inclusion body myositis.
Reducing the amount of blood transfused: a systematic review of behavioral interventions to change physicians' transfusion practices
Archives of Internal Medicine. 2005;165((8):):845-52.
BACKGROUND Transfusion services have used various techniques to reduce blood product utilization. Given the potential adverse effects of transfusions and the resources consumed in implementing strategies to reduce transfusions, there is a need to understand their effectiveness. Therefore, we performed a systematic review of the literature to examine the effectiveness of behavioral interventions to reduce blood product utilization. METHODS We identified all relevant articles through the use of electronic searches of MEDLINE and EMBASE, as well as hand searches of review articles and personal files. The electronic searches included articles published between January 1966 and May 2003. The searches included the terms blood transfusion, plasma exchange, guidelines, education, practice patterns, and professional practice. The outcomes of interest were the number of units transfused and the proportion of patients who received transfusions. RESULTS Nineteen studies examining the effectiveness of single (guidelines, prospective audits, retrospective audits, and reminders) or multifaceted interventions in reducing red blood cell, platelet, plasma, cryoprecipitate, and albumin transfusions met the inclusion criteria. Eighteen studies demonstrated a relative reduction in the number of units given (range, 9%-77%) or the proportion of patients receiving transfusions (range, 17%-79%). The reported reductions were qualitatively similar for the different blood products studied. No particular intervention or combination of interventions appeared more effective in reducing utilization. CONCLUSIONS Behavioral interventions, including simple interventions, appear to be effective in changing physician transfusion practices and reducing blood utilization. Appropriately designed clinical trials are still needed to determine the relative effectiveness of different interventions to change practices.
Use of intravenous immunoglobulin for treatment of neurological conditions: a systematic review
Blood. 2004;104((11):):990a.. Abstract No. 3642.