Effect of Recent Antirheumatic Drug on Features of Rheumatoid Arthritis–Associated Lymphoproliferative Disorders
Yoshihiko Hoshida, Atsuko Tsujii, Shiro Ohshima, Yukihiko Saeki, Masato Yagita, Tomoya Miyamura, Masao Katayama, Tomonori Kawasaki, Yasushi Hiramatsu, Hisaji Oshima, Toshihiko Murayama, Shinji Higa, Kazuya Kuraoka, Fuminori Hirano, Kenji Ichikawa, Mitsutoshi Kurosawa, Hiroaki Suzuki, Noriyuki Chiba, Takao Sugiyama, Yuko Minami, Hitoshi Niino, Atsushi Ihata, Ikuo Saito, Akiko Mitsuo, Toshitaka Maejima, Atsuhiro Kawashima, Hiroshi Tsutani, Koichiro Takahi, Takahiko Kasai, Yoko Shinno, Yoshiro Tachiyama, Norihiro Teramoto, Kenichi Taguchi, Shinji Naito, Shigeru Yoshizawa, Masahiro Ito, Yasuo Suenaga, Shunsuke Mori, Shoichi Nagakura, Norie Yoshikawa, Mitsuharu Nomoto, Atsuhisa Ueda, Shouhei Nagaoka, Yukio Tsuura, Keigo Setoguchi, Shoji Sugii, Asami Abe, Toshiaki Sugaya, Hiroyuki Sugahara, Shigeki Fujita, Yasuo Kunugiza, Norishige Iizuka, Ryosuke Yoshihara, Hiroki Yabe, Tomoaki Fujisaki, Eiichi Morii, Morishige Takeshita, Masakazu Sato, Kazuyoshi Saito, Kiyoshi Matsui, Yasuhiko Tomita, Hiroshi Furukawa, Shigeto Tohma
Abstract
OBJECTIVE: In this study, we examine how advancements in novel antirheumatic drugs affect the clinicopathologic features of lymphoproliferative disorder (LPD) in patients with rheumatoid arthritis (RA). METHODS: In this multicenter study across 53 hospitals in Japan, we characterized patients with RA who developed LPDs and visited the hospitals between January 1999 and March 2021. The statistical tools used included Fisher's exact test, the Mann-Whitney U-test, the log-rank test, logistic regression analysis, and Cox proportional hazards models. RESULTS: Overall, 752 patients with RA-associated LPD (RA-LPD) and 770 with sporadic LPD were included in the study. We observed significant differences in the clinicopathologic features between patients with RA-LPD and those with sporadic LPD. Histopathological analysis revealed a high frequency of LPD-associated immunosuppressive conditions. Furthermore, patients with RA-LPD were evaluated based on the antirheumatic drugs administered. The methotrexate (MTX) plus tacrolimus and MTX plus tumor necrosis factor inhibitor (TNFi) groups had different affected site frequencies and histologic subtypes than the MTX-only group. Moreover, MTX and TNFi may synergistically affect susceptibility to Epstein-Barr virus infection. In case of antirheumatic drugs administered after LPD onset, tocilizumab (TCZ)-only therapy was associated with lower frequency of regrowth after spontaneous regression than other regimens. CONCLUSION: Antirheumatic drugs administered before LPD onset may influence the clinicopathologic features of RA-LPD, with patterns changing over time. Furthermore, TCZ-only regimens are recommended after LPD onset.