THU0149 A clinical and pathological characterization of methotrexate-associated lymphoproliferative disorders in patients with rheumatoid arthritis
Authors: K Nakano, A Nawata, S Nakayamada, S Iwata, K Hanami, S Kubo, I Miyagawa, M Yoshikawa, K Saito, Y Tanaka
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Methotrexate (MTX) is used as an anchor drug for the treatment of rheumatoid arthritis (RA). Patients with RA have a modestly increased risk of developing lymphoproliferative disorders (LPD). Furthermore, although sometimes spontaneous regression occurs after withdrawal of MTX, LPD developed during the treatment with MTX is broadly defined as MTX-associated LPD (MTX-LPD). <h3>Objectives</h3> To characterize the risk factors concerning MTX-LPD and to consider optimal treatment after occurrence of LPD in patients with RA. <h3>Methods</h3> We retrospectively evaluated 51 RA patients with LPD from 2006 to 2015 in our institution. MTX-LPD patients were divided into two groups; regressive LPD after MTX cessation (N=27) and persistent LPD though MTX was tapered (N=24), and the clinical characteristics, pathology and treatment outcomes were compared. EBV infection and IL-6 receptor (IL-6R) expression were analyzed by in situ hybridization and immunohistochemistry. <h3>Results</h3> There was no significant difference in disease duration, stage, disease activity of RA, the positive rate of Epstein–Barr virus-encoded small RNAs, EBERs (42.7 vs 50.0%) and treatment with TNF-inhibitors (40.7 vs 45.8%) between regressive LPD and persistent LPD. Age of LPD onset (59.1 vs 68.3), CRP (2 vs 5 mg/dl) and the weekly MTX dose (10.9 vs 8.4 mg/w) significantly differed between the groups. Of note, IL-6R was highly expressed in both group (75.0 vs 66.7%). Among regressive LPD, 3 patients developed DLBCL later. persistent LPD showed poorer prognosis and worse mortality than regressive LPD. An older age and anemia were poor prognostic factors. Of 51 patients, 41% achieved sustained low disease activity (LDA) with other DMARDs except MTX. Nine of 10 patients refractory to DMARDs were controlled by tocilizumab (TCZ) and kept LDA. <h3>Conclusions</h3> Taken together, it seems unreasonable to be lump the persistent-group into the same category as MTX-LPD. The high expression rate of IL-6R and the high responsiveness to TCZ suggest that IL-6/IL-6R is likely to play a role in the development of LPD in patients with RA. <h3>Disclosure of Interest</h3> K. Nakano: None declared, A. Nawata: None declared, S. Nakayamada: None declared, S. Iwata: None declared, K. Hanami: None declared, S. Kubo Speakers bureau: Bristol-Myers, I. Miyagawa: None declared, M. Yoshikawa: None declared, K. Saito: None declared, Y. Tanaka Grant/research support from: Mitsubishi-Tanabe, Takeda, Daiichi-Sankyo, Chugai, Bristol-Myers, MSD, Astellas, Abbvie, Eisai, Consultant for: Abbvie, Chugai, Daiichi-Sankyo, Bristol-Myers, Mitsubishi-Tanabe, Astellas, Takeda, Pfizer, Teijin, Asahi-kasei, YL Biologics, Sanofi, Janssen, Eli Lilly, GlaxoSmithKline, Speakers bureau: Abbvie, Chugai, Daiichi-Sankyo, Bristol-Myers, Mitsubishi-Tanabe, Astellas, Takeda, Pfizer, Teijin, Asahi-kasei, YL Biologics, Sanofi, Janssen, Eli Lilly, GlaxoSmithKline