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

• Published in: Modern rheumatology 2022-01, Vol.ahead-of-print (ahead-of-print), p.1-14
• Main Authors: Honda, Suguru, Sakai, Ryoko, Inoue, Eisuke, Majima, Masako, Konda, Naoko, Takada, Hideto, Kihara, Mari, Yajima, Nobuyuki, Nanki, Toshihiro, Yamamoto, Kazuhiko, Takeuchi, Tsutomu, Harigai, Masayoshi
• Format: Article
• Language: English
• Subjects: Antirheumatic Agents - adverse effects; Arthritis, Rheumatoid - complications; Arthritis, Rheumatoid - drug therapy; Female; Humans; Japan - epidemiology; Lymphoma, Large B-Cell, Diffuse; lymphoproliferative disorder; Lymphoproliferative Disorders - chemically induced; Lymphoproliferative Disorders - epidemiology; methotrexate; Methotrexate - adverse effects; Middle Aged; Retrospective Studies; rheumatoid arthritis; risk
• ISSN: 1439-7595; 1439-7609
• DOI: 10.1080/14397595.2020.1869370

To investigate the risk factors and clinical characteristics of lymphoproliferative disorder (LPD) in Japanese patients with rheumatoid arthritis (RA). 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. 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%). This nationwide study revealed risk factors, clinical characteristics, and prognosis of LPD in the largest number of Japanese patients with RA.