High plasma homocysteine level is associated with increased prevalence of the non-remission state in rheumatoid arthritis: Findings from the KURAMA cohort

Author:

Katsushima Masao12,Minamino Hiroto3ORCID,Shirakashi Mirei1,Onishi Akira4,Fujita Yoshihito3,Yamamoto Wataru5,Onizawa Hideo4,Tsuji Hideaki1,Watanabe Ryu24,Murakami Kosaku16,Fujii Takayuki47,Murata Koichi47,Tanaka Masao4,Inagaki Nobuya3,Morinobu Akio14,Hashimoto Motomu24

Affiliation:

1. Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University , Kyoto, Japan

2. Department of Clinical Immunology, Graduate School of Medicine, Osaka Metropolitan University , Osaka, Japan

3. Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University , Kyoto, Japan

4. Department of Advanced Medicine for Rheumatic Diseases, Graduate School of Medicine, Kyoto University , Kyoto, Japan

5. Department of Health Information Management, Kurashiki Sweet Hospital , Okayama, Japan

6. Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University , Kyoto, Japan

7. Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University , Kyoto, Japan

Abstract

ABSTRACT Objectives We aimed to determine the clinical impact of plasma homocysteine levels on disease activity and clinical remission in patients with rheumatoid arthritis (RA). Methods A cross-sectional study was conducted using KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) database. We enrolled 291 female patients, who were treated in a treat-to-target manner. We measured plasma total homocysteine using a liquid chromatography–tandem mass spectrometry system and collected clinical data including a 28-joint RA disease activity score-erythrocyte sedimentation rate (DAS28-ESR). Clinical remission of disease activity was defined as a DAS28-ESR < 2.6. Results In a univariable analysis, the plasma homocysteine concentration was significantly and positively associated with DAS-28-ESR and was higher in the non-remission group than in the remission group. The cutoff value of the plasma homocysteine level was calculated to be 7.9 nmol/mL by the test of the receiver operating characteristic curve analysis. In a multivariable analysis, after adjusting for clinically relevant variables, the high homocysteine level remained a significant positive association for DAS28-ESR (estimate 0.27, P = .0019) and a positive factor for the presence of RA non-remission (odds ratio 2.39, P = .0071). Conclusions Increased plasma homocysteine levels showed a significant positive association with current disease activity and the non-remission state in female patients with RA under treat-to-target treatment. The findings suggest the potential utility of plasma homocysteine as a disease state marker reflecting conditions that are treatment failure and difficult to remission and may provide clinical evidence on the interplay between homocysteine and inflammatory activation in RA.

Funder

Daiichi Sankyo Co., Ltd

Publisher

Oxford University Press (OUP)

Subject

Rheumatology

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