Outcomes of methotrexate-associated lymphoproliferative disorders in rheumatoid arthritis patients treated with disease-modifying anti-rheumatic drugs

Takuya Harada, Hiromi Iwasaki, Tsuyoshi Muta, Shingo Urata, Aiko Sakamoto, Kentaro Kohno, Ken Takase, Tomoya Miyamura, Takuya Sawabe, Hideki Asaoku, Kensuke Oryoji, Tomoaki Fujisaki, Yasuo Mori, Goichi Yoshimoto, Masahiro Ayano, Hiroki Mitoma, Toshihiro Miyamoto, Hiroaki Niiro, Hidetaka Yamamoto, Yumi OshiroHiroaki Miyoshi, Koichi Ohshima, Morishige Takeshita, Koichi Akashi, Koji Kato

Research output: Contribution to journalArticlepeer-review

Abstract

Recently, the use of targeted synthetic or biological disease-modifying anti-rheumatic drugs (ts/bDMARDs) in addition to conventional synthetic (cs)DMARDs including methotrexate (MTX) for rheumatoid arthritis (RA) has increased. However, whether ts/bDMARDs are associated with the development and clinicopathological features of MTX-associated lymphoproliferative disorder (MTX-LPD) in patients with RA remains unknown. Therefore, we evaluated the clinical outcomes of 121 patients with MTX-LPD. Results showed that prior use of ts/bDMARDs was not associated with the different histopathological subtypes of MTX-LPD. Patients with polymorphic-type LPD had a better event-free survival than those with diffuse large B-cell lymphoma (DLBCL), classical Hodgkin lymphoma and peripheral T-cell lymphoma. The pathological subtype of lymphoma could predict the clinical outcome of MTX-LPD. In patients with DLBCL, the use of tumour necrosis factor-alpha (TNF-α) inhibitors prior to MTX-LPD onset was associated with a higher non-relapse mortality. Further, patients with RA previously treated with Janus kinase (JAK) inhibitors more commonly required chemotherapy than those treated with csDMARDs alone, indicating disease aggressiveness. Hence, special caution should be observed when managing patients with MTX-LPD previously treated with JAK or TNF-α inhibitors for RA.

Original languageEnglish
JournalBritish Journal of Haematology
DOIs
Publication statusAccepted/In press - 2021

All Science Journal Classification (ASJC) codes

  • Hematology

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