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Recent advances in treatments of adult immune thrombocytopenia.

ABSTRACT: Immune thrombocytopenia (ITP) is isolated thrombocytopenia characterized by autoimmune-mediated disruption of platelet without other etiologies. Treatments for chronic ITP consist of corticosteroids, intravenous immunoglobulins, anti-D immunoglobulin, rituximab, thrombopoietin receptor agonists, immunosuppressants and splenectomy. Although current therapies are effective in over two-thirds of patients, some patients are refractory to therapies or fail to achieve long-term responses. Recently, great advance has been made in identifying various mechanisms involved in ITP pathogenesis, and new treatments targeting these pathways are being developed. Novel agents such as splenic tyrosine kinase inhibitor, Bruton kinase inhibitor, plasma cell targeting therapies, neonatal Fc receptor inhibitor, platelet desialylation inhibitor, and inhibition of the classical complement pathway are expected to be effective for ITP treatment. This review summarizes current strategies and emerging therapies of ITP.

SUBMITTER: Kim DS

PROVIDER: S-EPMC9057657 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Recent advances in treatments of adult immune thrombocytopenia.

Kim Dae Sik DS

Blood research 20220401 S1

Immune thrombocytopenia (ITP) is isolated thrombocytopenia characterized by autoimmune-mediated disruption of platelet without other etiologies. Treatments for chronic ITP consist of corticosteroids, intravenous immunoglobulins, anti-D immunoglobulin, rituximab, thrombopoietin receptor agonists, immunosuppressants and splenectomy. Although current therapies are effective in over two-thirds of patients, some patients are refractory to therapies or fail to achieve long-term responses. Recently, gr ...[more]

PMID: 35483935

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Project description:BackgroundImmune thrombocytopenia is an autoimmune disease characterised by decreased platelet count. In recent years, novel therapeutic regimens have been investigated in randomised controlled trials (RCTs). We aimed to compare the efficacy and safety of different treatments in newly diagnosed adult primary immune thrombocytopenia.MethodsWe did a systematic review and network meta-analysis of RCTs involving treatments for newly diagnosed primary immune thrombocytopenia. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched up to April 31, 2022. The primary outcomes were 6-month sustained response and early response. Secondary outcome was grade 3 or higher adverse events. This study is registered with PROSPERO (CRD42022296179).FindingsEighteen RCTs (n = 1944) were included in this study. Pairwise meta-analysis showed that the percentage of patients achieving early response was higher in the dexamethasone-containing doublet group than in the dexamethasone group (79.7% vs 68.7%, odds ratio [OR] 1.82, 95% CI 1.10-3.02). The difference was more profound for sustained response (60.5% vs 37.4%, OR 2.57, 95% CI 1.95-3.40). Network meta-analysis showed that dexamethasone plus recombinant human thrombopoietin ranked first for early response, followed by dexamethasone plus oseltamivir or tacrolimus. Rituximab plus prednisolone achieved highest sustained response, followed by dexamethasone plus all-trans retinoic acid or rituximab. Rituximab plus dexamethasone showed 15.3% of grade 3 or higher adverse events, followed by prednis(ol)one (4.8%) and all-trans retinoic acid plus dexamethasone (4.7%).InterpretationOur findings suggested that compared with monotherapy dexamethasone or prednis(ol)one, the combined regimens had better early and sustained responses. rhTPO plus dexamethasone ranked top in early response, while rituximab plus corticosteroids obtained the best sustained response, but with more adverse events. Adding oseltamivir, all-trans retinoic acid or tacrolimus to dexamethasone reached equally encouraging sustained response, without compromising safety profile. Although this network meta-analysis compared all the therapeutic regimens up to date, more head-to-head RCTs with larger sample size are warranted to make direct comparison among these strategies.FundingNational Natural Science Foundation of China, Major Research Plan of National Natural Science Foundation of China, Shandong Provincial Natural Science Foundation and Young Taishan Scholar Foundation of Shandong Province.

Project description:Gastric cancer (GC) is the fifth most common cancer worldwide. Despite recent improvements in treatment quality and options, advanced gastric cancer remains one of the hardest to cure cancers, with a median overall survival (OS) of 10-12 months and a 5-year OS of approximately 5-20%. There is an unmet need for further efforts to palliate disease-related symptoms, improve quality of life, increase tumor response rate, and prolong progression free and overall survival while balancing the toxicities of therapy. The most common type of GC is adenocarcinoma, which demonstrates morphological, biological, and clinical heterogeneity. A plethora of genomic alterations and the activation of numerous molecular pathways including human epidermal growth receptor 2 (HER2), epidermal growth factor receptor (EGFR), fibroblast growth factor receptor-2 (FGFR2), mesenchymal epidermal transforming factor receptor (MET), and the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) are responsible for the complex heterogeneity of GC. Efforts to validate the therapeutic effects of inhibiting some of these aberrantly expressed pathways have failed to lead to a clinically meaningful outcome apart from the overexpression/amplification of the HER2 gene, inhibition of which has had a significant impact on clinical practice. The only available biomarkers to guide the effective treatment of patients with advanced GC are HER2 overexpression, MSI/PD-L1 status, and FGFR alterations. Various anti-HER2 agents have been evaluated after the success of the ToGA trial, but none led to a significant enough clinical improvement to be considered a viable alternative for HER2-targeted therapy in advanced GC until the global Keynote-811 trial, which added pembrolizumab to trastuzumab in combination with chemotherapy. This combination demonstrated a survival advantage for the first time in the 11 years since ToGA. Trastuzumab deruxtecan (T-DXd) was also found to be effective in patients who had already received >2 previous lines of treatment. Despite these promising avenues, the optimal management of HER-2 positive GC still requires further development.

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Recent advances in treatments of adult immune thrombocytopenia.

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Recent advances in treatments of adult immune thrombocytopenia.

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