Fostamatinib for the treatment of immune thrombocytopenia in adults

Moore, Donald C; Gebru, Tsion; Muslimani, Alaa

doi:10.1093/ajhp/zxz052

Cited by 13 publications

(8 citation statements)

References 27 publications

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“…The indications of fostamatinib are, in addition to RA, conditions such as acute myeloid leukemia, chronic lymphocytic leukemia, lymphoma, immune thrombocytopenia, autoimmune hemolytic anemia, and IgA nephropathy ( Friedberg et al, 2010 ; Morales-Torres, 2010 ; Efremov & Laurenti, 2011 ; Bartaula-Brevik et al, 2018 ; Markham, 2018 ). Overall, fostamatinib is generally well tolerated, but the most common adverse events include hypertension, diarrhea, dizziness, nausea, epistaxis, abnormal liver function tests, and infections, which are mild or moderate and can be resolved by medication or relieved spontaneously ( Bussel et al, 2018 ; Bussel et al, 2019 ; Moore et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

The Cardiovascular Risks of Fostamatinib in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

et al. 2021

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Objective: This systematic review and meta-analysis is aimed at assessing the risks of cardiovascular adverse events in patients with rheumatoid arthritis (RA) who have been treated with fostamatinib.Methods: The electronic databases of OVID Medline, OVID EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science were searched to identify studies that reported cardiovascular events or hypertension in RA patients treated with fostamatinib. Two reviewers separately and simultaneously screened the retrieved studies based on study selection criteria, collected data and performed methodological quality assessments. The effect size of meta-analysis was estimated by the Peto odds ratio (OR) or relative risk (RR) with 95% confidence intervals (95%CI). Funnel plot was used to estimate publication bias and sensitivity analysis was performed to test the robustness of the results.Results: A total of 12 trials composed of 5,618 participants with low to moderate risk of bias were included. In comparison to the placebo, the use of fostamatinib was found to elevate the risk of hypertension (RR=3.82, 95%CI 2.88–5.05) but was not associated with the risks of all-cause death (Peto OR=0.16, 95%CI 0.02–1.24), major adverse cardiovascular events (Peto OR=1.24, 95%CI 0.26–5.97), pulmonary heart disease and disease of pulmonary circulation (Peto OR=1.23, 95%CI 0.13–11.87), in addition to other forms of heart disease (Peto OR=1.96, 95%CI 0.72–5.38). Furthermore, sensitivity analysis showed no significant change in effective trends and no publication bias was found.Conclusion: Fostamatinib is associated with increased risk of hypertension; however, no increased risks of cardiovascular events were observed. Further well-planned cohort studies with large study populations and longer follow-up times are needed to elucidate the outcomes.Systematic Review Registration: [PROSPERO], identifier [CRD42020198217].

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Section: Discussionmentioning

confidence: 99%

The Cardiovascular Risks of Fostamatinib in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

et al. 2021

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“…Fostamatinib is an inhibitor of CDK1 and CHEK1 and is approved by the United States Food and Drug Administration for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia ( 27 , 28 ). The drug is also being assessed for potential indications, such as chronic lymphocytic leukemia and solid tumors ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

Key genes involved in cell cycle arrest and DNA damage repair identified in anaplastic thyroid carcinoma using integrated bioinformatics analysis

Zhang¹,

Zou²,

Dai³

et al. 2020

Transl Cancer Res TCR

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Background: Since anaplastic thyroid carcinoma (ATC) has rapid progression and a poor outcome, identification of the key genes and underlying mechanisms of ATC is required.Methods: Gene expression profiles of GSE29265 and GSE33630 were available from the Gene Expression Omnibus database. The two profile datasets included 19 ATC tissues, 55 normal thyroid tissues and 59 papillary thyroid cancer (PTC) tissues. Differentially expressed genes (DEGs) between ATC tissues and normal thyroid tissues as well as ATC tissues and PTC tissues were identified using the GEO2R tool.Common DEGs between the two datasets were selected via Venn software online. Then, we applied the Database for Annotation, Visualization and Integrated Discovery for Kyoto Encyclopedia of Gene and Genome pathway and gene ontology (GO) analyses. Additionally, protein-protein interactions (PPIs) of these DEGs were visualized via Cytoscape with Search Tool for the Retrieval of Interacting Genes. In the PPI networks analyzed by the Molecular Complex Detection plug-in, all 54 upregulated core genes were selected. Furthermore, Kaplan-Meier analysis was applied to analyze overall survival based on these 54 genes. Then, we used the DrugBank database to identify drug relationships for the 54 genes. Additionally, we validated the correlations between genes enriched in pathways and genes identified as prognosis biomarkers of THCA by Gene Expression Profiling Interactive Analysis.Results: Four genes (CCNB1, CCNB2, CDK1 and CHEK1) involved cell cycle arrest and DNA repair were significantly enriched in the G2/M phase of the cell cycle pathway and before G2 phase arrest of the P53 pathway. Inhibitors of CHEK1, CDK1 and TOP2A were identified in the DrugBank database. ANLN, DEPDC1, KIF2C, CENPN, TACC3 CCNB2 and CDC6 were hypothesized to be prognostic biomarkers of ATC. Furthermore, CCNB1, CCNB2, CDK1 and CHEK1 were significantly positively associated with these prognosis genes.Conclusions: CCNB1, CCNB2, CDK1 and CHEK1 may be key genes involved cell cycle arrest and DNA damage repair in ATC. Further studies are required to confirm the contributions of the identified genes to ATC progression and survival.

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“…Furthermore, pimozide has been demonstrated that its treatment resulted in the decreased level of BCL2 [76]. In addition to the treatment of chronic immune thrombocytopenia [77], there is a study showing that repurposing of fostamatinib is an effective treatment to inhibit metastatic tumor outgrowth in breast cancer [78]. Moreover, evidence has demonstrated that fostamatinib could also prevent the promotion of pro-tumorigenic microenvironment mediated by B-cell [79].…”

Section: The Identified Biomarkers and Their Corresponding Potential Multiple-molecule Drug To Prevent The Progression From Early To Middmentioning

confidence: 99%

Systems Medicine Design based on Systems Biology Approaches and Deep Neural Network for Gastric Cancer

Yeh

Chen

2022

IEEE/ACM Trans. Comput. Biol. and Bioinf.

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Gastric cancer (GC) is the third leading cause of cancer death in the world. It is associated with the stimulation of microenvironment, aberrant epigenetic modification, and chronic inflammation. However, few researches discuss the GC molecular progression mechanisms from the perspective of the system level. In this study, we proposed a systems medicine design procedure to identify essential biomarkers and find corresponding drugs for GC. At first, we did big database mining to construct candidate protein-protein interaction network (PPIN) and candidate gene regulation network (GRN). Secondly, by leveraging the next-generation sequencing (NGS) data, we performed system modeling and applied system identification and model selection to obtain real genome-wide genetic and epigenetic networks (GWGENs). To make the real GWGENs easy to analyze, the principal network projection method was used to extract the core signaling pathways denoted by KEGG pathways. Subsequently, based on the identified biomarkers, we trained a deep neural network of drug-target interaction (DeepDTI) with supervised learning and filtered our candidate drugs considering drug regulation ability and drug sensitivity. With the proposed systematic strategy, we not only shed the light on the progression of GC but also suggested potential multiple-molecule drugs efficiently.

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Fostamatinib for the treatment of immune thrombocytopenia in adults

Cited by 13 publications

References 27 publications

The Cardiovascular Risks of Fostamatinib in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

The Cardiovascular Risks of Fostamatinib in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

Key genes involved in cell cycle arrest and DNA damage repair identified in anaplastic thyroid carcinoma using integrated bioinformatics analysis

Systems Medicine Design based on Systems Biology Approaches and Deep Neural Network for Gastric Cancer

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