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Abstract Number: 463

Treatment with Biologic Agents for RA in Patients with MTX-Associated Lymphoproliferative Disorders

Takayuki Katsuyama1, Ken-ei Sada1, Noriko Toyota-Tatebe2, Katsue S. Watanabe1, Toru Kiguchi3 and Jun Wada2, 1Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan, 2Department of Medicine and Clinical Science,, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan, 3Department of Internal Medicine, Chugoku Central Hospital, Fukuyama, Japan

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: methotrexate (MTX) and rheumatoid arthritis (RA)

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Session Information

Date: Sunday, November 8, 2015

Title: Rheumatoid Arthritis - Clinical Aspects Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

Methotrexate (MTX) is known as an anchor drug for the treatment of rheumatoid arthritis (RA), and MTX-associated lymphoproliferative disorders (MTX-LPD) is of current interest. However, clinical course and optimum therapies in the patients with MTX-LPD remain uncharacterized.

Methods:

We enrolled RA patients who had been diagnosed as LPD during MTX therapy from January 2009 to December 2014. Baseline data including age, sex and duration of RA and MTX treatment were collected. Histopathological diagnosis, Epstein–Barr encoding region (EBER) in situ and serum EB virus (EBV) DNA were assessed. We evaluated the relationship between the characteristics and clinical outcome of LPD. We also described the clinical course and the treatment for RA after the diagnosis of MTX-LPD.

Results:

Twenty-two patients (17 female and 5 male) were enrolled in this study. The age at the diagnosis of LPD was 68.4 ± 9.0 years and they were treated for 15.5 ± 14.7 years and under the treatment of MTX for 80.6 ± 80.2 months. Biopsy was performed in 18 patients, and 10 of them (55.6 %) were diagnosed as diffuse large B cell lymphoma and 2 as marginal zone B cell lymphoma. EBER in situ was positive in 10 of 17 patients (58.8%), and the serum EBVDNA was detected in 8 of 11 (72.7%). MTX was withdrawn immediately after the diagnosis of LPD in all cases. The withdrawal resulted in the remission of LPD in 18 cases (81.8%, non-chemotherapy group), whereas 4 cases required chemotherapy (chemotherapy group). Serum EBVDNA was positive in all patients of non-chemotherapy group, while negative in all of chemotherapy group (p= 0.0003). The positive rate of EBER in situ was not significantly different between two groups (61.5 % vs. 50.0%, p=0.682). Age and the duration of MTX treatment were comparable whereas the history of RA was significantly longer in chemotherapy group than in non-chemotherapy group (29 years vs. 13 years, p= 0.0035). After the diagnosis of LPD, they were treated for 37.3 ± 22 months, and the relapse or exacerbation of RA was observed in 13 patients (61.9 %) after 9.2 ± 10 months. Nine patients were treated with various biologic agents, excluding rituximab, for RA relapse. The eight of nine patient sustained LPD remission after treatment with biologic agents; however one case was diagnosed as angioimmunoblastic T cell lymphoma and experienced recurrence of LPD during tocilizumab (TCZ) therapy. She was treated with chemotherapy. TCZ was switched to other biologic agents, and no recurrence of LPD was observed. There was no difference of the duration of RA and the positive rate of EBER and EBVDNA between patients with and without RA relapse after LPD diagnosis.

Conclusion:

The present study revealed that the positivity of serum EBVDNA was useful to predict the better clinical outcome of MTX-LPD. There was no established evidence of biologic therapies in RA patients with MTX-LPD but they seem to be effective and rather safe for most of RA patients after MTX-LPD diagnosis.


Disclosure: T. Katsuyama, None; K. E. Sada, None; N. Toyota-Tatebe, None; K. S. Watanabe, None; T. Kiguchi, None; J. Wada, None.

To cite this abstract in AMA style:

Katsuyama T, Sada KE, Toyota-Tatebe N, Watanabe KS, Kiguchi T, Wada J. Treatment with Biologic Agents for RA in Patients with MTX-Associated Lymphoproliferative Disorders [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/treatment-with-biologic-agents-for-ra-in-patients-with-mtx-associated-lymphoproliferative-disorders/. Accessed .
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