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福斯他替尼在原发性慢性免疫性血小板减少症治疗中的应用与定位:意大利专家意见

Use and positioning of fostamatinib in the management of primary chronic immune thrombocytopenia: an Italian expert opinion.

作者信息

Lucchesi Alessandro, Fattizzo Bruno, De Stefano Valerio, Ruggeri Marco, Siragusa Sergio, Vianelli Nicola, Zaja Francesco, Rodeghiero Francesco

机构信息

Hematology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy.

Department of Oncology and Onco-Hematology, University of Milan, via Festa del Perdono 7, 20122 Milan, Italy.

出版信息

Ther Adv Hematol. 2023 Feb 28;14:20406207221147777. doi: 10.1177/20406207221147777. eCollection 2023.

Abstract

Fostamatinib, a spleen tyrosine kinase (Syk) inhibitor, represents a new therapeutic opportunity for patients with immune thrombocytopenia (ITP) in Europe and Italy. However, the positioning of this drug in patient's therapeutic sequence is undefined within the most recent international guidelines. The conclusions from a consensus meeting between Italian experts, whose task was to outline the profile of the ideal candidate to receive fostamatinib, are reported here. A modified Delphi methodology was used to achieve shared statements, which were reported in a narrative form. In particular, the panelists examined the strengths and weaknesses of the registration studies in terms of clinical outcomes, the safety profile of fostamatinib, the drug's impact on the quality of life of patients with chronic ITP, and the potential benefits of its use in the pandemic era. Although the experience with thrombopoietin receptor agonists (TPO-RAs) and the amount of data from real-world studies suggest the preferential use of these drugs as a second-line treatment in most patients, the absence of an increased thrombotic risk in the clinical trials could make fostamatinib a reasonable choice in patients with an increased risk of vascular events. An unstable platelet count during TPO-RAs might also justify a switch to the Syk inhibitor, which is more likely to stabilize the platelet count in responders. Fostamatinib may be preferred to immunosuppressors during the SARS-CoV-2 pandemic, in patients at infectious risk, or in case of contraindication to splenectomy. Finally, the novel mechanism of action makes it an attractive drug in multi-refractory patient.

摘要

fostamatinib是一种脾酪氨酸激酶(Syk)抑制剂,为欧洲和意大利的免疫性血小板减少症(ITP)患者带来了新的治疗机遇。然而,在最新的国际指南中,这种药物在患者治疗序列中的定位尚不明确。本文报告了意大利专家共识会议的结论,该会议旨在勾勒出接受fostamatinib的理想候选者的特征。采用了改良的德尔菲方法来达成共同声明,并以叙述形式进行了报告。具体而言,小组成员研究了注册研究在临床结果方面的优缺点、fostamatinib的安全性、该药物对慢性ITP患者生活质量的影响以及在大流行时代使用它的潜在益处。尽管血小板生成素受体激动剂(TPO-RAs)的使用经验和来自真实世界研究的数据量表明,在大多数患者中优先将这些药物用作二线治疗,但临床试验中未发现血栓形成风险增加,这可能使fostamatinib成为血管事件风险增加患者的合理选择。TPO-RAs治疗期间血小板计数不稳定也可能成为改用Syk抑制剂的理由,因为Syk抑制剂更有可能使反应者的血小板计数稳定。在SARS-CoV-2大流行期间、有感染风险的患者或脾切除禁忌的情况下,fostamatinib可能比免疫抑制剂更受青睐。最后,这种新的作用机制使其成为多难治性患者中一种有吸引力的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75a4/10326469/b164301959f8/10.1177_20406207221147777-fig1.jpg

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