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

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.