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

Mod Rheumatol. 2022 Jan 5;32(1):16-23. doi: 10.1080/14397595.2020.1869370.

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.

Keywords: lymphoproliferative disorder; methotrexate; rheumatoid arthritis; risk.

MeSH terms

  • Antirheumatic Agents* / adverse effects
  • Arthritis, Rheumatoid* / complications
  • Arthritis, Rheumatoid* / drug therapy
  • Female
  • Humans
  • Japan / epidemiology
  • Lymphoma, Large B-Cell, Diffuse*
  • Lymphoproliferative Disorders* / chemically induced
  • Lymphoproliferative Disorders* / epidemiology
  • Methotrexate / adverse effects
  • Middle Aged
  • Retrospective Studies

Substances

  • Antirheumatic Agents
  • Methotrexate