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In this retrospective study, we evaluated the actual incidence, prognostic impact, and risk factors of MTX\u2010LPD. Of the 986 patients with RA treated with MTX, 90 patients experienced 95 new malignancies (NMs), with LPD as the most frequent in 26 patients. The cumulative LPD incidences were 1.3% and 4.7% at 5 and 10\u2009years after MTX initiation, respectively. Among the 24 patients who discontinued MTX after developing LPD, 15 showed sustained regression, without difference in overall survival between patients with LPD and without NM. Inflammatory markers and absolute lymphocyte counts were not useful for early LPD development detection, but most of the patients with LPD had persistently elevated erythrocyte sedimentation ratios. Regarding concomitant drugs, tacrolimus increased the risk only if patients were not receiving biological disease\u2010modifying antirheumatic drugs (bDMARDs). bDMARDs did not increase the risk for any of the drugs or the number of classes used. The number of LPD cases was lower in patients with IL\u20106A even after a long period after MTX, although with no statistically significant difference. Thus, approximately 1 in 20 patients with RA developed MTX\u2010LPD over the 10\u2009years of MTX treatment, but it did not affect the survival of patients with RA. Tacrolimus increased the risk of developing LPD for certain patients and should be used with caution.<\/jats:p>","DOI":"10.1111\/cas.15894","type":"journal-article","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T01:41:00Z","timestamp":1687830060000},"page":"3719-3727","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Lymphoproliferative disorder risk after methotrexate treatment for rheumatoid arthritis"],"prefix":"10.1111","volume":"114","author":[{"given":"Keisuke","family":"Tanaka","sequence":"first","affiliation":[{"name":"Department of Hematology Tokyo Medical and Dental University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Department of Hematology Tokyo Medical and Dental University  Tokyo 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