Department of Advanced Medicine, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8560, Japan.
Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan.
Int J Hematol. 2020 Dec;112(6):841-850. doi: 10.1007/s12185-020-02972-0. Epub 2020 Sep 1.
Many drugs are used for unapproved indications in Japan for post hematopoietic stem cell transplant (HCT) complications. To investigate unapproved or off-label drug usage for graft-versus-host disease (GVHD) and virus infections after allogeneic HCT, we analyzed the data of Japanese HCT registry. Between 2006 and 2017, 39,941 adults and children received HCT for a variety of disease and their transplant data were captured in the registry. Among them, 14,687 and 8914 patients receiving treatment for acute and/or chronic GVHD, 24,828 patients with cytomegalovirus (CMV) infection or receiving therapies for CMV, and 4943 who received treatment for other viral infections were included in the analyses of off-label or unapproved drugs. For GVHD, mycophenolate mofetil was the most frequently used off-label drug, followed by beclomethasone, infliximab, and etanercept. For viral infections other than CMV, foscarnet was the most frequently used off-label drug. Cidofovir, which is not approved for use in Japan, was mainly used for adenovirus infection. This study demonstrated that numerous off-label and unapproved drugs have been used as key drugs for GVHD and post-transplant viral infection, and the real world date in the transplant registry may serve as an important asset to regulatory purposes.
许多药物在日本被用于造血干细胞移植（HCT）后并发症的未经批准的适应症。为了研究异基因 HCT 后移植物抗宿主病（GVHD）和病毒感染的未经批准或标签外药物使用情况，我们分析了日本 HCT 注册处的数据。在 2006 年至 2017 年期间，有 39941 名成人和儿童因各种疾病接受 HCT，其移植数据被捕获在注册处。其中，有 14687 名和 8914 名患者接受急性和/或慢性 GVHD 的治疗，24828 名患者患有巨细胞病毒（CMV）感染或接受 CMV 的治疗，4943 名患者接受其他病毒感染的治疗，这些患者均被纳入标签外或未经批准药物的分析。对于 GVHD，霉酚酸酯是最常用的标签外药物，其次是倍氯米松、英夫利昔单抗和依那西普。对于 CMV 以外的其他病毒感染，喷昔洛韦是最常用的标签外药物。在日本未获准使用的更昔洛韦主要用于腺病毒感染。本研究表明，许多标签外和未经批准的药物已被用作 GVHD 和移植后病毒感染的关键药物，移植登记处的真实世界数据可能成为监管目的的重要资产。
