Association of methotrexate use and lymphoproliferative disorder in patients with rheumatoid arthritis: Results from a Japanese multi-institutional retrospective study

Abstract

Abstract Objectives To investigate the risk factors and clinical characteristics of lymphoproliferative disorder (LPD) in Japanese patients with rheumatoid arthritis (RA). Methods We enrolled patients with RA aged ≥20 years who visited the participating hospitals between April 2011 and July 2011. We investigated the risk factors for LPD using a Cox proportional hazard model and described pathological features and vital prognosis of LPD in patients with RA. Results We enrolled 9815 patients with the following characteristics at baseline: female 79.4%, median age 63 years; median disease duration 7 years; median DAS28-CRP (3) 3.1; prevalence of MTX use 60.0%. Sixty-eight patients (0.69%) developed LPD in 3-year observation period. Multivariable analysis showed that age by decade (hazard ratio [95% confidence interval], 1.47 [1.18–1.85]) and MTX use at baseline (2.35 [1.25–4.42] for ≤8 mg/week, 4.39 [2.07–9.32] for >8 mg/week versus non-use) were significant risk factors of LPD. Of 55 patients with pathological diagnosis, diffuse large B cell lymphoma was the most frequent (54%). The 5-year mortality of LPD was 24%. The major cause of death was lymphoma (81%). Conclusion This nationwide study revealed risk factors, clinical characteristics, and prognosis of LPD in the largest number of Japanese patients with RA.