Background/Purpose: Lymphoproliferative disorders (LPDs) are a serious complication in patients with rheumatoid arthritis (RA). Methotrexate (MTX) is known to be able to cause a development of LPDs and previous reports have shown that the cumulative dose of MTX and combination therapy with immunosuppressive agents influence the risk of developing LPDs. However, few reports have focused on the duration from the initiation of MTX to the onset of LPDs. Therefore, the aim of this study is to clarify the factors that influencing the time until the development of LPDs in patients with RA being treated with MTX.

Methods: RA patients who developed LPDs during MTX therapy at Tokai University Hospital between 2001 and 2017 were retrospectively examined. We collected demographic and clinical characteristics and pathological findings from the medical records. The duration from the initiation of MTX to the development of LPDs was calculated. The association between the duration from the initiation of MTX until the development of LPDs and various parameters were analyzed by univariate and multivariate analyses.

Results: A total of 45 patients with RA who developed LPD during MTX therapy were found. Eight patients were excluded from the analysis because of incomplete data and 37 patients (mean 66 years of age) were enrolled. Folic acid (FA), biological disease-modifying anti-rheumatic diseases (bDMARDs), conventional synthetic DMARDs (csDMARDs) and corticosteroid were used in 14, 8 and 16 patients, respectively. The mean duration to the development of LPDs from the first administration of MTX was 6.8 years. In the univariate analysis, the combined use of FA with MTX significantly prolonged the period between the time of MTX initiation and the development of LPDs compared to MTX monotherapy (3.6 years vs. 9.0 years, p < 0.001). In addition, we found that the time until the development of LPDs was prolonged in a dose-dependent manner (3.0 years at 0mg; 6.2years at 3mg; 8.7 years at 5mg). In contrast, combination therapy with csDMARDs significantly shortened the time until the development of LPDs compared to without csDMARDs combination therapy (5.1 years vs. 7.9 years, p = 0.04). However, no significant association was noted between the time until the development of LPDs and the combined use of bDMARDs or corticosteroids. Complication with Sjögren’s syndrome did not influence the time until the development of LPDs. A multiple regression analysis revealed that the combined use of FA was an independent factor that prolonged the time until the development of LPDs (p<0.01).

Conclusion: These results indicated that the combined use of FA with MTX might prolong the time until the development of LPDs during MTX treatment in RA patients.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-combined-use-of-folic-acid-influenced-the-time-until-the-development-of-lymphoproliferative-disorders-in-patients-with-rheumatoid-arthritis-during-treatment-with-methotrexate/