Use of unapproved or off-label drugs in Japan for the treatment of graft-versus-host disease and post-transplant viral infection

• Published in: International journal of hematology Vol. 112; no. 6; pp. 841 - 850
• Main Authors: Kuwatsuka, Yachiyo, Atsuta, Yoshiko, Hirakawa, Akihiro, Uchida, Naoyuki, Inamoto, Yoshihiro, Najima, Yuho, Ikegame, Kazuhiro, Eto, Tetsuya, Ozawa, Yukiyasu, Ichinohe, Tatsuo, Inoue, Masami, Kimura, Takafumi, Okamoto, Shinichiro, Miyamura, Koichi, Fukuda, Takahiro
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.12.2020; Springer Nature B.V
• Subjects: Acute Disease; Adult; Beclomethasone - therapeutic use; Chronic Disease; Chronic infection; Cidofovir; Cidofovir - therapeutic use; Complications; Cytomegalovirus; Cytomegalovirus Infections - drug therapy; Cytomegalovirus Infections - etiology; Drugs; Etanercept; Etanercept - therapeutic use; Female; Foscarnet; Foscarnet - therapeutic use; Graft versus host disease; Graft vs Host Disease - drug therapy; Graft vs Host Disease - etiology; Graft-versus-host reaction; Hematology; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic stem cells; Humans; Immunosuppressive agents; Infections; Infliximab; Infliximab - therapeutic use; Japan; Male; Medical treatment; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Mycophenolate mofetil; Mycophenolic acid; Mycophenolic Acid - therapeutic use; Off-Label Use; Oncology; Original Article; Postoperative Complications - drug therapy; Postoperative Complications - etiology; Registries; Stem cell transplantation; Stem cells; Transplantation, Homologous; Tumor necrosis factor-α; Viral infections; Virus Diseases - drug therapy; Virus Diseases - etiology; Viruses; Japan; Graft-versus-host disease; Stem cell transplantation; Drug lag; Registry; Post-transplant viral infection
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-020-02972-0

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.