Background Rheumatoid arthritis (RA) patients are sometimes associated with lymphoproliferative disorders (LPD), including lymphoid proliferation and lymphoma, in balance with the disease itself  or related to treatment with methotrexate (MTX) or biologics. Spontaneous LPD regression sometimes occurs after withdrawal MTX and/or biologics. The critical driving forces from lymphoid proliferation to lymphoma has not been apparent and the treatment for RA after a LPD is a major concern.
Objectives To investigate the clinical courses and treatments for RA patients after a LPD in daily practice.
Methods Among RA patients who self-reported lymphadenopathy in the IORRA observational cohort study in October 2012, patients who developed lymphadenopathy in the context of RA or RA treatment confirmed by their medical records were extracted. Histopathological examinations of lymph nodes, and treatment for RA at the time of lynphoadenopathy and after recovery from a LPD were investigated.
Results We extracted 48 RA patients who developed a LPD, which included 25 who had malignant lymphoma (ML), 16 who had benign lymphoadenopathy defined by biopsy, and 7 who had lymphoadenopathy that disappeared prior to biopsy.
Among ML patients [20 females (80.0%); RA onset: 51.2 years; RA duration: 10.9 years], 14 (56.0%) had been taking MTX, 1 (4.0%) had received an anti-tumor necrosis factor (anti-TNF) agent, and the others had received conventional DMARDs or no treatment. Seventeen patients (68.0%) received chemotherapy, 1 received H. pylori eradication, and 5 (20.0%) who had lymphoma (4 with diffuse large B cell lymphoma and 1 with immunoblastic lymphoadenopathy) that disappeared after withdrawal MTX received no additional chemotherapy. No patients with lymphoma were treated for RA with MTX or biologics except 1 case with MTX after that. ML had not recurred in all 25 patients for 72.0 (3-192) months. Among 23 patients with lymphoadenopathy but not ML [20 females (87.0%); RA onset age: 48.5 years; disease duration: 12.0 years], all had been taking MTX [mono therapy for 15 (65.2%), combination with anti-TNF agents for 3 (13.0%) and tacrolimus for 3 (13.0%)] when lymphoadenopathy developed. All these patients, except 1, had stopped MTX and that patient stopped etanercept (ETN). LPD disappeared in 22 patients and lymphoademopathy had regressed but remained in 1. Five (21.7%) patients were re-treated with MTX after 27.5 (6-49) months from lymphoadenopathy regression, and 9 (39.1%) were started on biologics (ETN for 7, abatacept for 1 and tocilizumab for 1) after 36.0 (2-70) months from lymphoadenopathy regression. Lymphadenopathy had not recurred in all 23 patients for 36.1 (9-126) months.
Conclusions Withdrawal either MTX or biologics for RA patients with lymphoadenopathy might be essential. MTX or anti-TNF agents were not introduced for RA treatment after lymphoma in Japan where rituximab was not approved. Whereas re-administering MTX or introducing biologics, such as anti-TNF or anti-IL-6 agents, were used for patients without recurrence who had lymphoid proliferation. Histological analysis should be considered for future treatment planning.
Hellgren K, et al. Arthritis Rheum 2010;62:1252-58.
Disclosure of Interest Y. Shimizu: None declared, A. Nakajima: None declared, E. Inoue: None declared, A. Kobayashi: None declared, K. Shidara: None declared, N. Sugimoto: None declared, D. Hoshi: None declared, E. Sato: None declared, Y. Seto: None declared, E. Tanaka: None declared, S. Momohara Speakers bureau: Abbvie Japan, Chugai Parmaceutical, Eisai, Mitsubishi Tanabe Parma, Takeda ParmaceuticalA., A. Taniguchi: None declared, H. Yamanaka Grant/research support: Abbott, AbbVie, Asahikasei, Astellas, AstraZeneca, Bristol-Myers Squib, Chugai, Daiichi Sankyo, Eisai, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, MSD, Nippon Kayaku, Pfizer, Santen, Taishotoyama, Takeda, Teijin Consultant for: Abbott, AbbVie, Astellas, AstraZeneca, Bristol-Myers Squib, Chugai, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, Nippon Kayaku, Pfizer, Takeda, Teijin, Speakers bureau: Abbott, AbbVie, Astellas, Bristol-Myers Squib, Chugai, Eisai, Mitsubishi Tanabe, Pfizer, Takeda, Teijin