Clinical aspects in patients with rheumatoid arthritis complicated with lymphoproliferative disorders without regression after methotrexate withdrawal and treatment for arthritis after regression of lymphoproliferative disorders

Abstract

Objectives

To identify predictive factors for lymphoproliferative disorders (LPDs) that persist after methotrexate (MTX) withdrawal (Persistent-LPD) and the optimal treatment for rheumatoid arthritis (RA) after LPD regression.

Methods

Among 3666 patients with RA treated with MTX in our department from 2006 to 2017, 26 cases of LPD that regressed after MTX withdrawal (Regressive-LPD) and 25 cases of Persistent-LPD were compared. Multivariate logistic analysis was performed to identify predictive factors for Persistent-LPD. Retention rates of biological disease-modifying antirheumatic drugs (bDMARDs) were calculated using the Kaplan–Meier Method.

Results

In Persistent-LPD, the incidence of diffuse large B-cell lymphoma was higher (76%). The overall 2-year survival rate was 83.9%: 95.8% for Regressive-LPD and 71.0% for Persistent-LPD. The International Prognostic Index (IPI) risk classification was useful for predicting Persistent-LPD. bDMARDs were introduced in 38 RA patients after LPD regression. Unadjusted retention rate of bDMARDs in the 51 LPD patients was significantly lower than that in the 1668 non-LPD RA patients in our bDMARD cohort (controls) (p = 0.029). The 1-year retention rates for bDMARDs were 69% and 64% for tocilizumab and abatacept, respectively vs. 46% for TNF-inhibitor (TNFi).

Conclusion

Risk assessment using IPI predicted Persistent-LPD. After LPD regression, non-TNFi tended to have higher retention rates.

Keywords:

• Rheumatoid arthritis
• methotrexate
• lymphoproliferative disorders
• biological disease-modifying antirheumatic drugs

Conflict of interest

K. Nakano has received speaking fees from Astellas, UCB, Mitsubishi-Tanabe, Eisai and has received research grants from Mitsubishi-Tanabe, Eisai, and Eli Lilly. S. Kubo has received speaking fees from Bristol-Myers, Eli Lilly, Pfizer, and Takeda. S. Nakayamada has received speaking fees from Bristol-Myers, Sanofi, Abbvie, Eisai, Chugai, Pfizer, Takeda, Asahi-kasei and also research grants from Mitsubishi-Tanabe, Novartis and MSD. Y. Tanaka, has received speaking fees and/or honoraria from Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, Abbvie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Teijin and has received research grants from Asahi-kasei, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Ono.