Dataset Information

Risk of Bleeding Associated With Ibrutinib in Patients With B-Cell Malignancies: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

ABSTRACT: Background: Ibrutinib is an oral covalent Bruton's tyrosine kinase inhibitor that has been approved for chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia and some other B-cell malignancies. Some studies have found an increased risk of bleeding with ibrutinib. Some studies, however, found no significant differences in the risk of major bleeding between patients treated with ibrutinib and those with other regimens. So, a systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to estimate the risk of bleeding associated with ibrutinib in patients with B-cell malignancies. Methods: A systematic search of PUBMED, EMBASE, Central Register of Controlled Trials, and ClinicalTrials.gov was conducted from January 2000 to February 2020 to identify RCTs by comparing ibrutinib with other agents or placebo in B-cell malignancies. The RevMan software (version 5.3) was used to carry out this analysis, and the analyzed data were represented by risk ratios (RR) and 95% confidence intervals (CI). Results: There were 11 eligible RCTs (4,288 patients). All studies reported major bleeding, and seven studies reported overall bleeding (any-grade bleeding). Ibrutinib was associated with a significantly increased risk of bleeding (overall bleeding and major bleeding) in patients with B-cell malignancies [RR = 2.56, 95% CI 1.68-3.90, p < 0.0001 and RR = 2.08, 95% CI 1.36-3.16, p = 0.0006, respectively]. The bleeding (overall bleeding and major bleeding) risk in patients with CLL was more obvious [RR = 3.08, 95% CI 2.07-4.58, p < 0.00001 and RR = 2.46, 95% CI 1.37-4.41, p = 0.003, respectively]. There were no statistically significant differences for risk of bleeding between the subgroups based on dose and treatment setting. Conclusion: Ibrutinib was associated with a significantly higher risk of bleeding (both overall bleeding and major bleeding) in patients with B-cell malignancies, especially in CLL.

SUBMITTER: Wang J

PROVIDER: S-EPMC7919192 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Risk of Bleeding Associated With Ibrutinib in Patients With B-Cell Malignancies: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Wang Jinjin J Zhao Ailin A Zhou Hui H Zhu Jinbing J Niu Ting T

Frontiers in pharmacology 20201120

<b>Background:</b> Ibrutinib is an oral covalent Bruton's tyrosine kinase inhibitor that has been approved for chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia and some other B-cell malignancies. Some studies have found an increased risk of bleeding with ibrutinib. Some studies, however, found no significant differences in the risk of major bleeding between patients treated with ibrutinib and those with other regimens. So, a systematic review and meta-analysis of randomized controll ...[more]

PMID: 33658926

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Project description:In 2012, the United States Food and Drug Administration (FDA) issued a warning regarding potential adverse effects of HMG-CoA reductase inhibitors (statins) on cognition, based on the Adverse Events Reporting System and a review of the medical literature. We aimed to synthesize randomized clinical trial (RCTs) evidence on the association between statin therapy and cognitive outcomes.We searched MEDLINE, EMBASE, and Cochrane CENTRAL through December 2012, and reviewed published systematic reviews of statin treatment. We sought RCTs that compared statin treatment versus placebo or standard care, and reported at least one cognitive outcome (frequency of adverse cognitive events or measurements using standard neuropsychological cognitive test scores). Studies reporting sufficient information to calculate effect sizes were included in meta-analyses. Standardized and unstandardized mean differences were calculated for continuous outcomes for global cognition and for pre-specified cognitive domains. The main outcome was change in cognition measured by neuropsychological tests; an outcome of secondary interest was the frequency of adverse cognitive events observed during follow-up.We identified 25 RCTs (all placebo-controlled) reporting cognitive outcomes in 46,836 subjects, of which 23 RCTs reported cognitive test results in 29,012 participants. Adverse cognitive outcomes attributable to statins were rarely reported in trials involving cognitively normal or impaired subjects. Furthermore, meta-analysis of cognitive test data (14 studies; 27,643 participants) failed to show significant adverse effects of statins on all tests of cognition in either cognitively normal subjects (standardized mean difference 0.01, 95% confidence interval, CI, -0.01 to 0.03, p?=?0.42) or Alzheimer's disease subjects (standardized mean difference -0.05, 95% CI -0.19 to 0.10, p?=?0.38).Statin therapy was not associated with cognitive impairment in RCTs. These results raise questions regarding the continued merit of the FDA warning about potential adverse effects of statins on cognition.

Project description:Objective(s)Edoxaban, a factor Xa inhibitor, is a new oral anticoagulant that has been developed as an alternative to vitamin K antagonists. However, its safety remains unexplored.MethodsMedline, Embase and Web of Science were searched to March 8, 2014 for prospective, randomized controlled trials (RCTs) that assessed the safety profile of edoxaban with warfarin. Safety outcomes examined included bleeding risk and mortality.ResultsFive trials including 31,262 patients that met the inclusion criteria were pooled. Overall, edoxaban was associated with a significant decrease in major or clinically relevant nonmajor bleeding events [risk ratio (RR) 0.78, 95% confidence interval (CI) 0.74 to 0.82, p<0.001] and any bleeding events [RR 0.82, 95% CI 0.79 to 0.85, p<0.001]. Edoxaban also showed superiority to warfarin both in all-cause mortality [RR 0.92, 95% CI 0.85 to 0.99, p = 0.02] and cardiovascular mortality [RR 0.87, 95% CI 0.79 to 0.96, p = 0.004]. Subgroup analyses indicated that RRs of edoxaban 30, 60 or 120 mg/d were 0.67 (p<0.001), 0.87 (p<0.001) and 3.3 (p = 0.004) respectively in major or clinically relevant nonmajor bleeding; 0.71 (p<0.001), 0.89 (p<0.001) and 2.29 (p = 0.002) respectively in any bleeding; as well as 0.86 (p = 0.01), 0.87 (p = 0.01) and 0.28 (p = 0.41) respectively in cardiovascular death… Meanwhile, paramount to note that pooled results other than the largest trial showed edoxaban was still associated with a decrease in the rate of major or clinically relevant nonmajor bleeding event (p = 0.02) and any bleeding (p = 0.002), but neither in all-cause death (p = 0.66) nor cardiovascular death (p = 0.70).ConclusionsEdoxaban, a novel orally available direct factor Xa inhibitor, seems to have a favorable safety profiles with respect to bleeding risk and non-inferior in mortality when compared to warfarin. Further prospective RCTs are urgently needed to confirm the results of this meta-analysis.

Dataset Information

Risk of Bleeding Associated With Ibrutinib in Patients With B-Cell Malignancies: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Publications

Risk of Bleeding Associated With Ibrutinib in Patients With B-Cell Malignancies: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

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