Reduction of plasma IL-6 but not TNF-α by methotrexate in patients with early rheumatoid arthritis: A potential biomarker for radiographic progression

Naoshi Nishina, Yuko Kaneko, Hideto Kameda, Masataka Kuwana, Tsutomu Takeuchi

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30 Citations (Scopus)

Abstract

Objective: To determine the effect of methotrexate (MTX) on plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α and to investigate their associations with clinical and radiographic responses in patients with early rheumatoid arthritis (RA). Methods: Sixty-two untreated RA patients with the disease duration of ≤36 months in whom MTX was initiated were consecutively identified in our prospective RA cohort and included in this study. Concomitant use of prednisolone and synthetic disease-modifying anti-rheumatic drugs with MTX was allowed, but patients who used biological agents were excluded. Plasma IL-6 and TNF-α levels were measured at the time of diagnosis (baseline) and 1 year later. The relationships of the clinical and radiographic data with plasma levels of IL-6 and TNF-α were analyzed. Results: The median age of the patients was 57 years, 49 patients were female, and the median disease duration was 3 months. Forty-six (74.2 %) patients were anti-cyclic citrullinated protein antibody-positive. Serum C-reactive protein (CRP), plasma IL-6, and DAS28 decreased significantly (p <0.001) after MTX treatment, but plasma TNF-α did not. Radiographic progression was significantly correlated with disease activity score and plasma IL-6 levels but not with CRP or TNF-α after MTX treatment. Patients with plasma IL-6 level above 4.03 pg/ml showed clinically relevant radiographic progression with a sensitivity of 91.7 % and a specificity of 88.0 %. Conclusion: In this early RA cohort, we demonstrated a significant (p <0.001) reduction of plasma IL-6, but not TNF-α, during MTX treatment. The post-treatment IL-6 level was a strong indicator of radiographic progression.

Original languageEnglish
Pages (from-to)1661-1666
Number of pages6
JournalClinical Rheumatology
Volume32
Issue number11
DOIs
Publication statusPublished - 2013 Nov

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Methotrexate
Interleukin-6
Rheumatoid Arthritis
Tumor Necrosis Factor-alpha
Biomarkers
C-Reactive Protein
Antirheumatic Agents
Biological Factors
Therapeutics
Prednisolone
Blood Proteins
Antibodies
Proteins

Keywords

  • Interleukin-6
  • Methotrexate
  • Rheumatoid arthritis
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Rheumatology

Cite this

@article{778e3fc456e5433cbee6c87cb4f17215,
title = "Reduction of plasma IL-6 but not TNF-α by methotrexate in patients with early rheumatoid arthritis: A potential biomarker for radiographic progression",
abstract = "Objective: To determine the effect of methotrexate (MTX) on plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α and to investigate their associations with clinical and radiographic responses in patients with early rheumatoid arthritis (RA). Methods: Sixty-two untreated RA patients with the disease duration of ≤36 months in whom MTX was initiated were consecutively identified in our prospective RA cohort and included in this study. Concomitant use of prednisolone and synthetic disease-modifying anti-rheumatic drugs with MTX was allowed, but patients who used biological agents were excluded. Plasma IL-6 and TNF-α levels were measured at the time of diagnosis (baseline) and 1 year later. The relationships of the clinical and radiographic data with plasma levels of IL-6 and TNF-α were analyzed. Results: The median age of the patients was 57 years, 49 patients were female, and the median disease duration was 3 months. Forty-six (74.2 {\%}) patients were anti-cyclic citrullinated protein antibody-positive. Serum C-reactive protein (CRP), plasma IL-6, and DAS28 decreased significantly (p <0.001) after MTX treatment, but plasma TNF-α did not. Radiographic progression was significantly correlated with disease activity score and plasma IL-6 levels but not with CRP or TNF-α after MTX treatment. Patients with plasma IL-6 level above 4.03 pg/ml showed clinically relevant radiographic progression with a sensitivity of 91.7 {\%} and a specificity of 88.0 {\%}. Conclusion: In this early RA cohort, we demonstrated a significant (p <0.001) reduction of plasma IL-6, but not TNF-α, during MTX treatment. The post-treatment IL-6 level was a strong indicator of radiographic progression.",
keywords = "Interleukin-6, Methotrexate, Rheumatoid arthritis, Tumor necrosis factor-alpha",
author = "Naoshi Nishina and Yuko Kaneko and Hideto Kameda and Masataka Kuwana and Tsutomu Takeuchi",
year = "2013",
month = "11",
doi = "10.1007/s10067-013-2309-0",
language = "English",
volume = "32",
pages = "1661--1666",
journal = "Clinical Rheumatology",
issn = "0770-3198",
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number = "11",

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TY - JOUR

T1 - Reduction of plasma IL-6 but not TNF-α by methotrexate in patients with early rheumatoid arthritis

T2 - A potential biomarker for radiographic progression

AU - Nishina, Naoshi

AU - Kaneko, Yuko

AU - Kameda, Hideto

AU - Kuwana, Masataka

AU - Takeuchi, Tsutomu

PY - 2013/11

Y1 - 2013/11

N2 - Objective: To determine the effect of methotrexate (MTX) on plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α and to investigate their associations with clinical and radiographic responses in patients with early rheumatoid arthritis (RA). Methods: Sixty-two untreated RA patients with the disease duration of ≤36 months in whom MTX was initiated were consecutively identified in our prospective RA cohort and included in this study. Concomitant use of prednisolone and synthetic disease-modifying anti-rheumatic drugs with MTX was allowed, but patients who used biological agents were excluded. Plasma IL-6 and TNF-α levels were measured at the time of diagnosis (baseline) and 1 year later. The relationships of the clinical and radiographic data with plasma levels of IL-6 and TNF-α were analyzed. Results: The median age of the patients was 57 years, 49 patients were female, and the median disease duration was 3 months. Forty-six (74.2 %) patients were anti-cyclic citrullinated protein antibody-positive. Serum C-reactive protein (CRP), plasma IL-6, and DAS28 decreased significantly (p <0.001) after MTX treatment, but plasma TNF-α did not. Radiographic progression was significantly correlated with disease activity score and plasma IL-6 levels but not with CRP or TNF-α after MTX treatment. Patients with plasma IL-6 level above 4.03 pg/ml showed clinically relevant radiographic progression with a sensitivity of 91.7 % and a specificity of 88.0 %. Conclusion: In this early RA cohort, we demonstrated a significant (p <0.001) reduction of plasma IL-6, but not TNF-α, during MTX treatment. The post-treatment IL-6 level was a strong indicator of radiographic progression.

AB - Objective: To determine the effect of methotrexate (MTX) on plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α and to investigate their associations with clinical and radiographic responses in patients with early rheumatoid arthritis (RA). Methods: Sixty-two untreated RA patients with the disease duration of ≤36 months in whom MTX was initiated were consecutively identified in our prospective RA cohort and included in this study. Concomitant use of prednisolone and synthetic disease-modifying anti-rheumatic drugs with MTX was allowed, but patients who used biological agents were excluded. Plasma IL-6 and TNF-α levels were measured at the time of diagnosis (baseline) and 1 year later. The relationships of the clinical and radiographic data with plasma levels of IL-6 and TNF-α were analyzed. Results: The median age of the patients was 57 years, 49 patients were female, and the median disease duration was 3 months. Forty-six (74.2 %) patients were anti-cyclic citrullinated protein antibody-positive. Serum C-reactive protein (CRP), plasma IL-6, and DAS28 decreased significantly (p <0.001) after MTX treatment, but plasma TNF-α did not. Radiographic progression was significantly correlated with disease activity score and plasma IL-6 levels but not with CRP or TNF-α after MTX treatment. Patients with plasma IL-6 level above 4.03 pg/ml showed clinically relevant radiographic progression with a sensitivity of 91.7 % and a specificity of 88.0 %. Conclusion: In this early RA cohort, we demonstrated a significant (p <0.001) reduction of plasma IL-6, but not TNF-α, during MTX treatment. The post-treatment IL-6 level was a strong indicator of radiographic progression.

KW - Interleukin-6

KW - Methotrexate

KW - Rheumatoid arthritis

KW - Tumor necrosis factor-alpha

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U2 - 10.1007/s10067-013-2309-0

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JO - Clinical Rheumatology

JF - Clinical Rheumatology

SN - 0770-3198

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