Prognostic factors of methotrexate-associated lymphoproliferative disorders associated with rheumatoid arthritis and plausible application of biological agents

Takayuki Katsuyama, Kenei Sada, Minglu Yan, Sonia Zeggar, Sumie Hiramatsu, Yoshia Miyawaki, Keiji Ohashi, Michiko Morishita, Haruki Watanabe, Eri Katsuyama, Mariko Takano-Narazaki, Noriko Toyota-Tatebe, Katsue Sunahori-Watanabe, Tomoko Kawabata, Kohei Miyake, Toru Kiguchi, Jun Wada

Research output: Contribution to journalArticle

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Abstract

Objectives: To determine prognostic factors of methotrexate-associated lymphoproliferative disorder (MTX-LPD) and evaluate the efficacy and safety of biological therapy in rheumatoid arthritis (RA) complicated with MTX-LPD. Methods: Thirty RA patients who developed MTX-LPD were investigated in this study. We compared the clinical and laboratory parameters of patients who achieved regression of LPD by MTX withdrawal with those who required chemotherapy and evaluated the clinical course of RA after LPD development. Results: Twenty-three patients (76.7%) achieved regression of LPD by MTX withdrawal. Chemotherapy-free patients had a tendency of shorter RA duration (13.1 vs. 22.0 years, p = 0.108) and higher doses of MTX at LPD diagnosis (8.0 vs. 5.3 mg/w, p = 0.067) than patients who required chemotherapy. A significantly higher positive rate of peripheral blood Epstein–Barr virus (EBV)-DNA was observed in the chemotherapy-free group (9/9 vs. 0/3, p = 0.0002). Of 15 patients that received biological agents after LPD development, 14 patients (93.3%) demonstrated an improved disease activity of RA and persistent remission of LPD, whereas only one patient experienced relapse of LPD during tocilizumab therapy. Conclusions: Peripheral blood EBV-DNA positivity is a potential prognostic marker of better outcome in MTX-LPD. Biological agents could be an option for the treatment of RA patients with MTX-LPD.

Original languageEnglish
Pages (from-to)1-5
Number of pages5
JournalModern Rheumatology
DOIs
Publication statusAccepted/In press - Dec 13 2016

Fingerprint

Lymphoproliferative Disorders
Biological Factors
Methotrexate
Rheumatoid Arthritis
Drug Therapy
DNA Viruses
Biological Therapy
Safety
Recurrence

Keywords

  • Biological therapy
  • Epstein–Barr virus
  • Methotrexate-associated lymphoproliferative disorders
  • Prognostic factors
  • Rheumatoid arthritis

ASJC Scopus subject areas

  • Rheumatology

Cite this

Prognostic factors of methotrexate-associated lymphoproliferative disorders associated with rheumatoid arthritis and plausible application of biological agents. / Katsuyama, Takayuki; Sada, Kenei; Yan, Minglu; Zeggar, Sonia; Hiramatsu, Sumie; Miyawaki, Yoshia; Ohashi, Keiji; Morishita, Michiko; Watanabe, Haruki; Katsuyama, Eri; Takano-Narazaki, Mariko; Toyota-Tatebe, Noriko; Sunahori-Watanabe, Katsue; Kawabata, Tomoko; Miyake, Kohei; Kiguchi, Toru; Wada, Jun.

In: Modern Rheumatology, 13.12.2016, p. 1-5.

Research output: Contribution to journalArticle

Katsuyama, T, Sada, K, Yan, M, Zeggar, S, Hiramatsu, S, Miyawaki, Y, Ohashi, K, Morishita, M, Watanabe, H, Katsuyama, E, Takano-Narazaki, M, Toyota-Tatebe, N, Sunahori-Watanabe, K, Kawabata, T, Miyake, K, Kiguchi, T & Wada, J 2016, 'Prognostic factors of methotrexate-associated lymphoproliferative disorders associated with rheumatoid arthritis and plausible application of biological agents', Modern Rheumatology, pp. 1-5. https://doi.org/10.1080/14397595.2016.1259714
Katsuyama, Takayuki ; Sada, Kenei ; Yan, Minglu ; Zeggar, Sonia ; Hiramatsu, Sumie ; Miyawaki, Yoshia ; Ohashi, Keiji ; Morishita, Michiko ; Watanabe, Haruki ; Katsuyama, Eri ; Takano-Narazaki, Mariko ; Toyota-Tatebe, Noriko ; Sunahori-Watanabe, Katsue ; Kawabata, Tomoko ; Miyake, Kohei ; Kiguchi, Toru ; Wada, Jun. / Prognostic factors of methotrexate-associated lymphoproliferative disorders associated with rheumatoid arthritis and plausible application of biological agents. In: Modern Rheumatology. 2016 ; pp. 1-5.
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abstract = "Objectives: To determine prognostic factors of methotrexate-associated lymphoproliferative disorder (MTX-LPD) and evaluate the efficacy and safety of biological therapy in rheumatoid arthritis (RA) complicated with MTX-LPD. Methods: Thirty RA patients who developed MTX-LPD were investigated in this study. We compared the clinical and laboratory parameters of patients who achieved regression of LPD by MTX withdrawal with those who required chemotherapy and evaluated the clinical course of RA after LPD development. Results: Twenty-three patients (76.7{\%}) achieved regression of LPD by MTX withdrawal. Chemotherapy-free patients had a tendency of shorter RA duration (13.1 vs. 22.0 years, p = 0.108) and higher doses of MTX at LPD diagnosis (8.0 vs. 5.3 mg/w, p = 0.067) than patients who required chemotherapy. A significantly higher positive rate of peripheral blood Epstein–Barr virus (EBV)-DNA was observed in the chemotherapy-free group (9/9 vs. 0/3, p = 0.0002). Of 15 patients that received biological agents after LPD development, 14 patients (93.3{\%}) demonstrated an improved disease activity of RA and persistent remission of LPD, whereas only one patient experienced relapse of LPD during tocilizumab therapy. Conclusions: Peripheral blood EBV-DNA positivity is a potential prognostic marker of better outcome in MTX-LPD. Biological agents could be an option for the treatment of RA patients with MTX-LPD.",
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T1 - Prognostic factors of methotrexate-associated lymphoproliferative disorders associated with rheumatoid arthritis and plausible application of biological agents

AU - Katsuyama, Takayuki

AU - Sada, Kenei

AU - Yan, Minglu

AU - Zeggar, Sonia

AU - Hiramatsu, Sumie

AU - Miyawaki, Yoshia

AU - Ohashi, Keiji

AU - Morishita, Michiko

AU - Watanabe, Haruki

AU - Katsuyama, Eri

AU - Takano-Narazaki, Mariko

AU - Toyota-Tatebe, Noriko

AU - Sunahori-Watanabe, Katsue

AU - Kawabata, Tomoko

AU - Miyake, Kohei

AU - Kiguchi, Toru

AU - Wada, Jun

PY - 2016/12/13

Y1 - 2016/12/13

N2 - Objectives: To determine prognostic factors of methotrexate-associated lymphoproliferative disorder (MTX-LPD) and evaluate the efficacy and safety of biological therapy in rheumatoid arthritis (RA) complicated with MTX-LPD. Methods: Thirty RA patients who developed MTX-LPD were investigated in this study. We compared the clinical and laboratory parameters of patients who achieved regression of LPD by MTX withdrawal with those who required chemotherapy and evaluated the clinical course of RA after LPD development. Results: Twenty-three patients (76.7%) achieved regression of LPD by MTX withdrawal. Chemotherapy-free patients had a tendency of shorter RA duration (13.1 vs. 22.0 years, p = 0.108) and higher doses of MTX at LPD diagnosis (8.0 vs. 5.3 mg/w, p = 0.067) than patients who required chemotherapy. A significantly higher positive rate of peripheral blood Epstein–Barr virus (EBV)-DNA was observed in the chemotherapy-free group (9/9 vs. 0/3, p = 0.0002). Of 15 patients that received biological agents after LPD development, 14 patients (93.3%) demonstrated an improved disease activity of RA and persistent remission of LPD, whereas only one patient experienced relapse of LPD during tocilizumab therapy. Conclusions: Peripheral blood EBV-DNA positivity is a potential prognostic marker of better outcome in MTX-LPD. Biological agents could be an option for the treatment of RA patients with MTX-LPD.

AB - Objectives: To determine prognostic factors of methotrexate-associated lymphoproliferative disorder (MTX-LPD) and evaluate the efficacy and safety of biological therapy in rheumatoid arthritis (RA) complicated with MTX-LPD. Methods: Thirty RA patients who developed MTX-LPD were investigated in this study. We compared the clinical and laboratory parameters of patients who achieved regression of LPD by MTX withdrawal with those who required chemotherapy and evaluated the clinical course of RA after LPD development. Results: Twenty-three patients (76.7%) achieved regression of LPD by MTX withdrawal. Chemotherapy-free patients had a tendency of shorter RA duration (13.1 vs. 22.0 years, p = 0.108) and higher doses of MTX at LPD diagnosis (8.0 vs. 5.3 mg/w, p = 0.067) than patients who required chemotherapy. A significantly higher positive rate of peripheral blood Epstein–Barr virus (EBV)-DNA was observed in the chemotherapy-free group (9/9 vs. 0/3, p = 0.0002). Of 15 patients that received biological agents after LPD development, 14 patients (93.3%) demonstrated an improved disease activity of RA and persistent remission of LPD, whereas only one patient experienced relapse of LPD during tocilizumab therapy. Conclusions: Peripheral blood EBV-DNA positivity is a potential prognostic marker of better outcome in MTX-LPD. Biological agents could be an option for the treatment of RA patients with MTX-LPD.

KW - Biological therapy

KW - Epstein–Barr virus

KW - Methotrexate-associated lymphoproliferative disorders

KW - Prognostic factors

KW - Rheumatoid arthritis

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