Background/Purpose

Lymphoproliferative disorder (LPD) is a rare complication in patients with rheumatoid arthritis(RA) treated with methotrexate(MTX). Although not a few patients experience exacerbation of RA disease activity after withdrawal of MTX, there have been very few reports referring how to treat RA with MTX-LPD. This study is to investigate the safety profile of biologic agents as a RA treatment after the diagnosis of MTX-LPD.

Methods

We retrospectively studied all 32 RA patients regarded as being complicated with MTX-LPD from 2007 to 2013 in our institution. The patients were classified into 2 groups: patients treated with biologic agents after MTX withdrawal (Biologics group) and patients treated with conventional synthetic disease modifying anti-rheumatic drugs (csDMARD) other than MTX or prednisolone (PSL) (non-biologics group). The rates of LPD recurrence after these RA treatments were compared. The recurrence rates were analyzed by Kaplan-Meier curves and compared by log-rank test.

Results

Four patients were excluded because three died before the restart of RA treatment and one needed no treatment, so twenty eight patients were analyzed in this study. Baseline characteristics of 28 patients were following: age,65; Female, 89%;  duration of MTX administration, 7.5 years; RA disease duration,14.1years; disease activity score (DAS) 28, 2.95. Of 28 patients, 22 patients were pathologically diagnosed as LPD, and 10 were highly suspected of LPD with imaging tests. Seven patients were treated of LPD with chemotherapy prior to restart of RA therapy. 17 Patients were treated with biologic agents and the drugs used were following; tocilizumab (TCZ) in 9 patients, tumor necrosis factor inhibitors (TNFi) in 6, abatacept in 1, rituximab in 1. Eleven patients were treated with PSL and/or csDMARDs; PSL alone in 5, salazosulfapyridin (SASP) in 3, bucillamin in 2, tacrolimus (Tac) in 1 patient. LPD relapsed in 2 patients in biologics group, and in 1 in non-biologics group. No significant difference in recurrence rates between the two groups analyzed by Kaplan-Meier curves and Log-rank test (Figure, p=0.84).

Among 7 patients who had been treated with chemotherapy before the RA disease activity exacerbation, 3 were treated with biologics and 4 with non-biologic; PSL alone in 2, SASP in 1, Tac in 1. No LPD recurrence was observed in these 7 patients in follow up duration (mean 33 months).

Additional analysis with 22 patients that were pathologically diagnosed of LPD showed similar results.

Conclusion

Biologics agents did not increase LPD recurrence compared to csDMARD, and could be the choice of RA treatment in post-MTX-LPD.

<Figure>Recurrence free RA treatment period [months]