Effect of Recent Antirheumatic Drug on Features of Rheumatoid Arthritis-Associated Lymphoproliferative Disorders

Yoshihiko Hoshida¹, Atsuko Tsujii¹, Shiro Ohshima¹, Yukihiko Saeki¹, Masato Yagita², Tomoya Miyamura³, Masao Katayama⁴, Tomonori Kawasaki⁴, Yasushi Hiramatsu⁵, Hisaji Oshima⁶, Toshihiko Murayama⁷, Shinji Higa⁸, Kazuya Kuraoka⁹, Fuminori Hirano¹⁰, Kenji Ichikawa¹¹, Mitsutoshi Kurosawa¹², Hiroaki Suzuki¹², Noriyuki Chiba¹³, Takao Sugiyama¹⁴, Yuko Minami¹⁵, Hitoshi Niino¹⁶, Atsushi Ihata¹⁶, Ikuo Saito¹⁷, Akiko Mitsuo¹⁸, Toshitaka Maejima¹⁹, Atsuhiro Kawashima²⁰, Hiroshi Tsutani²¹, Koichiro Takahi²², Takahiko Kasai²³, Yoko Shinno²⁴, Yoshiro Tachiyama²⁵, Norihiro Teramoto²⁶, Kenichi Taguchi²⁷, Shinji Naito²⁸, Shigeru Yoshizawa²⁹, Masahiro Ito³⁰, Yasuo Suenaga³¹, Shunsuke Mori³², Shoichi Nagakura³³, Norie Yoshikawa³⁴, Mitsuharu Nomoto³⁵, Atsuhisa Ueda³⁶, Shouhei Nagaoka³⁷, Yukio Tsuura³⁸, Keigo Setoguchi³⁹, Shoji Sugii⁴⁰, Asami Abe⁴¹, Toshiaki Sugaya⁴², Hiroyuki Sugahara⁴³, Shigeki Fujita⁴³, Yasuo Kunugiza⁴⁴, Norishige Iizuka⁴⁵, Ryosuke Yoshihara⁴⁶, Hiroki Yabe⁴⁷, Tomoaki Fujisaki⁴⁸, Eiichi Morii⁴⁹, Morishige Takeshita⁵⁰, Masakazu Sato⁵¹, Kazuyoshi Saito⁵², Kiyoshi Matsui⁵³, Yasuhiko Tomita⁵⁴, Hiroshi Furukawa⁵⁵, Shigeto Tohma⁵⁵

Affiliations

¹ National Health Organization (NHO) Osaka Minami Medical Center, Osaka, Japan.
² Tazuke-Kofukai Medical Research Institute Kitano Hospital, Osaka, Japan.
³ NHO Kyushu Medical Center, Fukuoka, Japan.
⁴ NHO Nagoya Medical Center, Nagoya, Japan.
⁵ Japanese Red Cross Society Himeji Hospital, Himeji, Japan.
⁶ NHO Tokyo Medical Center, Tokyo, Japan.
⁷ NHO Kumamoto Medical Center, Kumamoto, Japan.
⁸ Daini Osaka Police Hospital, Osaka, Japan.
⁹ NHO Kure Medical Center and Chugoku Cancer Center, Hiroshima, Japan.
¹⁰ NHO Asahikawa Medical Center, Asahikawa, Japan.
¹¹ NHO Hokkaido Medical Center, Sapporo, Japan.
¹² NHO Hokkaido Cancer Center, Sapporo, Japan.
¹³ NHO Morioka Medical Center, Morioka, Japan.
¹⁴ NHO Shimoshizu National Hospital, Yotsukaido, Japan.
¹⁵ NHO Ibarakihigashi National Hospital, Tokai, Japan.
¹⁶ NHO Yokohama Medical Center, Yokohama, Japan.
¹⁷ NHO Sagamihara National Hospital, Sagamihara, Japan.
¹⁸ NHO Disaster Medical Center, Tachikawa, Japan.
¹⁹ NHO Shinshu Ueda Medical Center, Nagano, Japan.
²⁰ NHO Kanazawa Medical Center, Kanazawa, Japan.
²¹ NHO Awara National Hospital, Fukui, Japan.
²² NHO Osaka Toneyama Medical Center, Toyonaka, Japan.
²³ NHO Kinki-Chuo Chest Medical Center, Sakai, Japan.
²⁴ NHO Okayama Medical Center, Okayama, Japan.
²⁵ NHO Hiroshimanishi Medical Center, Otake, Japan.
²⁶ NHO Shikoku Cancer Center, Matsuyama, Japan.
²⁷ NHO Kyushu Cancer Center, Fukuoka, Japan.
²⁸ NHO Ureshino Medical Center, Ureshino, Japan.
²⁹ NHO Fukuoka National Hospital, Fukuoka, Japan.
³⁰ NHO Nagasaki Medical Center, Nagasaki, Japan.
³¹ NHO Beppu Medical Center, Beppu, Japan.
³² Kumamoto Saishun Medical Center, Koshi, Japan.
³³ NHO Kumamotominami Hospital, Uki, Japan.
³⁴ NHO Miyakonojo Medical Center, Miyakonojo, Japan.
³⁵ NHO Kagoshima Medical Center, Kagoshima, Japan.
³⁶ Yokohama City University, Yokohama, Japan.
³⁷ Yokohama Minami Kyosai Hospital, Yokohama, Japan.
³⁸ Yokosuka Kyosai Hospital, Kanagawa, Japan.
³⁹ Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
⁴⁰ Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan.
⁴¹ Niigata Rheumatic Center, Shibata, Japan.
⁴² Fuchu Hospital, Fuchu, Japan.
⁴³ Sumitomo Hospital, Osaka, Japan.
⁴⁴ Japan Community Health Care Organization Hoshigaoka Medical Center, Hirakata, Japan.
⁴⁵ Kishiwada City Hospital, Kishiwada, Japan.
⁴⁶ Hyogo Prefectural Kakogawa Hospital, Kakogawa, Japan.
⁴⁷ Ako Central Hospital, Ako, Japan.
⁴⁸ Matsuyama Red Cross Hospital, Matsuyama, Japan.
⁴⁹ Osaka University, Suita, Japan.
⁵⁰ Fukuoka University, Fukuoka, Japan.
⁵¹ Kurashiki University of Science and the Arts, Kurashiki, Japan.
⁵² University of Occupational and Environmental Health, Kitakyushu, Japan.
⁵³ Hyogo Medical University, Hyogo, Japan.
⁵⁴ International University of Health and Welfare, Narita, Japan.
⁵⁵ NHO Tokyo National Hospital, Tokyo, Japan.

PMID: 38272827
DOI: 10.1002/art.42809

Multicenter Study

Effect of Recent Antirheumatic Drug on Features of Rheumatoid Arthritis-Associated Lymphoproliferative Disorders

Yoshihiko Hoshida et al. Arthritis Rheumatol. 2024 Jun.

. 2024 Jun;76(6):869-881.

doi: 10.1002/art.42809. Epub 2024 Mar 13.

Authors

Affiliations

¹ National Health Organization (NHO) Osaka Minami Medical Center, Osaka, Japan.
² Tazuke-Kofukai Medical Research Institute Kitano Hospital, Osaka, Japan.
³ NHO Kyushu Medical Center, Fukuoka, Japan.
⁴ NHO Nagoya Medical Center, Nagoya, Japan.
⁵ Japanese Red Cross Society Himeji Hospital, Himeji, Japan.
⁶ NHO Tokyo Medical Center, Tokyo, Japan.
⁷ NHO Kumamoto Medical Center, Kumamoto, Japan.
⁸ Daini Osaka Police Hospital, Osaka, Japan.
⁹ NHO Kure Medical Center and Chugoku Cancer Center, Hiroshima, Japan.
¹⁰ NHO Asahikawa Medical Center, Asahikawa, Japan.
¹¹ NHO Hokkaido Medical Center, Sapporo, Japan.
¹² NHO Hokkaido Cancer Center, Sapporo, Japan.
¹³ NHO Morioka Medical Center, Morioka, Japan.
¹⁴ NHO Shimoshizu National Hospital, Yotsukaido, Japan.
¹⁵ NHO Ibarakihigashi National Hospital, Tokai, Japan.
¹⁶ NHO Yokohama Medical Center, Yokohama, Japan.
¹⁷ NHO Sagamihara National Hospital, Sagamihara, Japan.
¹⁸ NHO Disaster Medical Center, Tachikawa, Japan.
¹⁹ NHO Shinshu Ueda Medical Center, Nagano, Japan.
²⁰ NHO Kanazawa Medical Center, Kanazawa, Japan.
²¹ NHO Awara National Hospital, Fukui, Japan.
²² NHO Osaka Toneyama Medical Center, Toyonaka, Japan.
²³ NHO Kinki-Chuo Chest Medical Center, Sakai, Japan.
²⁴ NHO Okayama Medical Center, Okayama, Japan.
²⁵ NHO Hiroshimanishi Medical Center, Otake, Japan.
²⁶ NHO Shikoku Cancer Center, Matsuyama, Japan.
²⁷ NHO Kyushu Cancer Center, Fukuoka, Japan.
²⁸ NHO Ureshino Medical Center, Ureshino, Japan.
²⁹ NHO Fukuoka National Hospital, Fukuoka, Japan.
³⁰ NHO Nagasaki Medical Center, Nagasaki, Japan.
³¹ NHO Beppu Medical Center, Beppu, Japan.
³² Kumamoto Saishun Medical Center, Koshi, Japan.
³³ NHO Kumamotominami Hospital, Uki, Japan.
³⁴ NHO Miyakonojo Medical Center, Miyakonojo, Japan.
³⁵ NHO Kagoshima Medical Center, Kagoshima, Japan.
³⁶ Yokohama City University, Yokohama, Japan.
³⁷ Yokohama Minami Kyosai Hospital, Yokohama, Japan.
³⁸ Yokosuka Kyosai Hospital, Kanagawa, Japan.
³⁹ Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan.
⁴⁰ Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan.
⁴¹ Niigata Rheumatic Center, Shibata, Japan.
⁴² Fuchu Hospital, Fuchu, Japan.
⁴³ Sumitomo Hospital, Osaka, Japan.
⁴⁴ Japan Community Health Care Organization Hoshigaoka Medical Center, Hirakata, Japan.
⁴⁵ Kishiwada City Hospital, Kishiwada, Japan.
⁴⁶ Hyogo Prefectural Kakogawa Hospital, Kakogawa, Japan.
⁴⁷ Ako Central Hospital, Ako, Japan.
⁴⁸ Matsuyama Red Cross Hospital, Matsuyama, Japan.
⁴⁹ Osaka University, Suita, Japan.
⁵⁰ Fukuoka University, Fukuoka, Japan.
⁵¹ Kurashiki University of Science and the Arts, Kurashiki, Japan.
⁵² University of Occupational and Environmental Health, Kitakyushu, Japan.
⁵³ Hyogo Medical University, Hyogo, Japan.
⁵⁴ International University of Health and Welfare, Narita, Japan.
⁵⁵ NHO Tokyo National Hospital, Tokyo, Japan.

PMID: 38272827
DOI: 10.1002/art.42809

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.

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References

REFERENCES

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1. Sokal EM, Antunes H, Beguin C, et al. Early signs and risk factors for the increased incidence of Epstein‐Barr virus‐related posttransplant lymphoproliferative diseases in pediatric liver transplant recipients treated with tacrolimus. Transplantation 1997;64:1438–1442.
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1. Younes BS, McDiarmid SV, Martin MG, et al. The effect of immunosuppression on posttransplant lymphoproliferative disease in pediatric liver transplant patients. Transplantation 2000;70:94–99.

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Effect of Recent Antirheumatic Drug on Features of Rheumatoid Arthritis-Associated Lymphoproliferative Disorders

Affiliations

Effect of Recent Antirheumatic Drug on Features of Rheumatoid Arthritis-Associated Lymphoproliferative Disorders

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