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

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.

Association between Rheumatoid Arthritis Disease Activity and Risk of Ovarian Malignancy in Middle-Aged and Elderly Women

“…This data suggested that patients with RA have an overall increased risk of developing cancer by 10% over the general population. Much evidence suggests that patients with RA have a significantly increased risk of lymphoma and lung cancer [ 14 – 20 ]. Lymphoma may be associated with MTX and bDMARDs in RA patients [ 14 – 16 ].…”

“…Much evidence suggests that patients with RA have a significantly increased risk of lymphoma and lung cancer [ 14 – 20 ]. Lymphoma may be associated with MTX and bDMARDs in RA patients [ 14 – 16 ]. And it was found that the higher the disease activity, the higher the relative risk [ 18 ], which is similar to the conclusion of our study.…”

Problems to Consider Before Determining the Regimen of the Treatment for Juvenile Systemic Sclerosis Treatment: A Case Report Where Tocilizumab Monotherapy Succeeded Efficiently and Safely

“…Thus far, various drugs to improve immune disorders and fibrosis have been used, 5 and recently, SHARE initiative has provided a recommendation based on expert opinion 6 that recommends corticosteroids, methotrexate (MTX), mycophenolate (MMF), or cyclophosphamide (CY), while hematopoietic stem-cell transplantation (HSCT) has been also recommended. However, from the experience of treating Japanese patients with rheumatoid arthritis, adverse reactions by MTX such as interstitial pneumonitis, liver injury, and lymphoproliferative disease tend to be more frequent in Japanese patients compared with other races 7 , 8 and coexisting ILD makes it difficult to use this agent. On the contrary, clinical trials have shown the effectiveness of CY in SSc, but these focused on patients older than 17 years of age, while some are retrospective studies or without control population.…”

Managing IBD in patients with previous cancers

“…Methotrexate use was linked with lymphoma as it was thought to adversely affect recognition of EBV-infected B lymphocytes; however, this evidence focused on patients with RA (where the risk of lymphoma is increased) often compared against the general population 23. A further retrospective study did, however, identify methotrexate as a risk factor for lymphoproliferative disorders versus non-use 24. Ultimately, there is little evidence to support that methotrexate alone is associated with malignancy in the context of IBD, although this may relate to small numbers of patients using this as monotherapy 25…”