Real-World Safety and Effectiveness of Letermovir in Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation: Final Results of Post-Marketing Surveillance in Japan.

IF 2.9 3区医学 Q2 PHARMACOLOGY & PHARMACY

Clinical Drug Investigation Pub Date : 2024-07-01 Epub Date: 2024-06-27 DOI:10.1007/s40261-024-01376-w

Masaki Fukuda, Junko Hattori, Rika Ohkubo, Asuka Watanabe, Shinichiroh Maekawa

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Abstract

Background and objective: Cytomegalovirus (CMV) is a common opportunistic infection after allogenic hematopoietic stem cell transplantation (allo-HSCT). Letermovir, an inhibitor of CMV DNA terminase, is approved for CMV prophylaxis in allo-HSCT patients. We report the final results of post-marketing surveillance of letermovir in Japan.

Methods: The case report forms were drafted in part by the Japanese Data Center for Hematopoietic Cell Transplantation using data elements in the Transplant Registry Unified Management Program and sent to individual HSCT centers to decrease the burden of reporting. Hematopoietic stem cell transplantation patients who received letermovir between May 2018 and May 2022 were registered. Data collected included physician-assessed adverse events/adverse drug reactions and clinical effectiveness (development of CMV disease, CMV antigen status, and use of preemptive therapy).

Results: A total of 821 HSCT patients were included in the safety analyses. Adverse drug reactions occurred in 11.33% of patients, with serious adverse drug reactions in 3.05%. The five most common adverse drug reactions were nausea (1.58%), renal impairment (1.46%), and acute graft versus host disease, CMV test positive, and hepatic function abnormal (0.61% each). A total of 670 patients were eligible for effectiveness analyses. Among these patients, 16.57% and 28.66% required preemptive therapy through week 14 and week 48, respectively. In addition, relatively few patients developed CMV disease throughout the follow-up period (1.34% at week 14 and 3.85% at week 48).

Conclusions: This final analysis of post-marketing surveillance with up to 48 weeks follow-up period in Japan provides further evidence supporting the safety profile and effectiveness of letermovir for CMV prophylaxis in patients undergoing allo-HSCT in real-world settings.

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来替莫韦在异基因造血干细胞移植患者中的实际安全性和有效性：日本上市后监测的最终结果。

背景与目的：巨细胞病毒（CMV）是异基因造血干细胞移植（allo-HSCT）后常见的机会性感染。来替莫韦是一种CMV DNA终止酶抑制剂，已被批准用于异基因造血干细胞移植患者的CMV预防。我们报告了来特莫韦在日本上市后的最终监测结果：病例报告表部分由日本造血细胞移植数据中心（Japanese Data Center for Hematopoietic Cell Transplantation）使用移植登记统一管理程序（Transplant Registry Unified Management Program）中的数据元素起草，并发送给各个造血干细胞移植中心，以减轻报告负担。登记了2018年5月至2022年5月期间接受过来特莫韦治疗的造血干细胞移植患者。收集的数据包括医生评估的不良事件/药物不良反应和临床疗效（CMV疾病的发展、CMV抗原状态和使用预防性治疗）：共有 821 名造血干细胞移植患者参与了安全性分析。11.33%的患者出现了药物不良反应，其中3.05%的患者出现了严重的药物不良反应。最常见的五种药物不良反应是恶心（1.58%）、肾功能损害（1.46%）、急性移植物抗宿主病、CMV 检测阳性和肝功能异常（各占 0.61%）。共有 670 名患者符合有效性分析的条件。在这些患者中，分别有 16.57% 和 28.66% 的患者在第 14 周和第 48 周需要进行预防性治疗。此外，在整个随访期间出现 CMV 疾病的患者相对较少（第 14 周为 1.34%，第 48 周为 3.85%）：日本上市后随访期长达 48 周的最终监测分析进一步证明了来特莫韦在实际环境中用于接受allo-HSCT的患者预防CMV的安全性和有效性。

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来源期刊

Clinical Drug Investigation 医学-药学

CiteScore

5.90

自引率

3.10%

发文量

108

审稿时长

6-12 weeks

期刊介绍： Clinical Drug Investigation provides rapid publication of original research covering all phases of clinical drug development and therapeutic use of drugs. The Journal includes: -Clinical trials, outcomes research, clinical pharmacoeconomic studies and pharmacoepidemiology studies with a strong link to optimum prescribing practice for a drug or group of drugs. -Clinical pharmacodynamic and clinical pharmacokinetic studies with a strong link to clinical practice. -Pharmacodynamic and pharmacokinetic studies in healthy volunteers in which significant implications for clinical prescribing are discussed. -Studies focusing on the application of drug delivery technology in healthcare. -Short communications and case study reports that meet the above criteria will also be considered. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Clinical Drug Investigation may be accompanied by plain language summaries to assist readers who have some knowledge, but non in-depth expertise in, the area to understand important medical advances.