MMP-3 as a predictor for structural remission in RA patients treated with MTX monotherapy

Kazuko Shiozawa, Takashi Yamane, Miki Murata, Ryosuke Yoshihara, Ken Tsumiyama, Shigeaki Imura, Shunichi Shiozawa

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Abstract

Background: The study was undertaken to assess the efficacy of methotrexate (MTX) monotherapy on the radiographic progression of individual rheumatoid arthritis (RA) patients, each of whom had received MTX monotherapy for 3 years with an option to change to biological disease-modifying anti-rheumatic drugs (bDMARDs). We also looked for predictors of radiographic non-progression in these patients. Methods: Rheumatoid patients (n = 161) were prospectively followed for 3 years while receiving low-dose MTX monotherapy unless disease was otherwise active and/or adverse events appeared. Their disease activity and radiographic progression were evaluated with reference to disease activity score 28 (DAS28), modified health assessment of questionnaire (mHAQ) and other indices. The change in van der Heijde-modified total Sharp score per year (TSS) was assessed using probability plots, in which the patients were classified into the subgroups showing structural remission (REM; TSS ≤0.5), radiographic progression (TSS >3) or rapid radiographic progression (RRP; TSS >5). Results: MTX monotherapy, continued until disease became active and/or adverse event appeared, was associated with a significant improvement (p <0.0001) in the DAS28-ESR (3) scores, % DAS28 remission, and mHAQ scores each year, from baseline to 3 years. The mHAQ remission rate (mHAQ <0.5) and Boolean remission were also improved from 16 to 60 % and 0.8 to 24.0 %, respectively. We found that the ratio of patients classified as REM increased yearly from 62/161 (38.5 %) to 69/137 (50.4 %), while those classified as TSS >3 decreased from 55/161 (34.2 %) to 28/137 (20.4 %) and those in RRP decreased from 35/161 (21.7 %) to 15/137 (10.9 %). Receiver operating characteristic (ROC) curve analyses showed that serum matrix metalloproteinase-3 (MMP-3) <103.7 ng/ml at outset predicts a patient subgroup that exhibits no radiographic progression. Conclusions: Half of rheumatoid patients treated with MTX monotherapy for 3 years exhibited structural remission, and this outcome can be predicted at the outset by lower serum MMP-3.

Original languageEnglish
Article number55
JournalArthritis Research and Therapy
Volume18
Issue number1
DOIs
Publication statusPublished - Feb 27 2016

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Matrix Metalloproteinase 3
Methotrexate
Rheumatoid Arthritis
Antirheumatic Agents
Serum
ROC Curve
Health

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Shiozawa, K., Yamane, T., Murata, M., Yoshihara, R., Tsumiyama, K., Imura, S., & Shiozawa, S. (2016). MMP-3 as a predictor for structural remission in RA patients treated with MTX monotherapy. Arthritis Research and Therapy, 18(1), [55]. https://doi.org/10.1186/s13075-016-0948-7

MMP-3 as a predictor for structural remission in RA patients treated with MTX monotherapy. / Shiozawa, Kazuko; Yamane, Takashi; Murata, Miki; Yoshihara, Ryosuke; Tsumiyama, Ken; Imura, Shigeaki; Shiozawa, Shunichi.

In: Arthritis Research and Therapy, Vol. 18, No. 1, 55, 27.02.2016.

Research output: Contribution to journalArticle

Shiozawa, K, Yamane, T, Murata, M, Yoshihara, R, Tsumiyama, K, Imura, S & Shiozawa, S 2016, 'MMP-3 as a predictor for structural remission in RA patients treated with MTX monotherapy', Arthritis Research and Therapy, vol. 18, no. 1, 55. https://doi.org/10.1186/s13075-016-0948-7
Shiozawa, Kazuko ; Yamane, Takashi ; Murata, Miki ; Yoshihara, Ryosuke ; Tsumiyama, Ken ; Imura, Shigeaki ; Shiozawa, Shunichi. / MMP-3 as a predictor for structural remission in RA patients treated with MTX monotherapy. In: Arthritis Research and Therapy. 2016 ; Vol. 18, No. 1.
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AU - Yamane, Takashi

AU - Murata, Miki

AU - Yoshihara, Ryosuke

AU - Tsumiyama, Ken

AU - Imura, Shigeaki

AU - Shiozawa, Shunichi

PY - 2016/2/27

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N2 - Background: The study was undertaken to assess the efficacy of methotrexate (MTX) monotherapy on the radiographic progression of individual rheumatoid arthritis (RA) patients, each of whom had received MTX monotherapy for 3 years with an option to change to biological disease-modifying anti-rheumatic drugs (bDMARDs). We also looked for predictors of radiographic non-progression in these patients. Methods: Rheumatoid patients (n = 161) were prospectively followed for 3 years while receiving low-dose MTX monotherapy unless disease was otherwise active and/or adverse events appeared. Their disease activity and radiographic progression were evaluated with reference to disease activity score 28 (DAS28), modified health assessment of questionnaire (mHAQ) and other indices. The change in van der Heijde-modified total Sharp score per year (TSS) was assessed using probability plots, in which the patients were classified into the subgroups showing structural remission (REM; TSS ≤0.5), radiographic progression (TSS >3) or rapid radiographic progression (RRP; TSS >5). Results: MTX monotherapy, continued until disease became active and/or adverse event appeared, was associated with a significant improvement (p <0.0001) in the DAS28-ESR (3) scores, % DAS28 remission, and mHAQ scores each year, from baseline to 3 years. The mHAQ remission rate (mHAQ <0.5) and Boolean remission were also improved from 16 to 60 % and 0.8 to 24.0 %, respectively. We found that the ratio of patients classified as REM increased yearly from 62/161 (38.5 %) to 69/137 (50.4 %), while those classified as TSS >3 decreased from 55/161 (34.2 %) to 28/137 (20.4 %) and those in RRP decreased from 35/161 (21.7 %) to 15/137 (10.9 %). Receiver operating characteristic (ROC) curve analyses showed that serum matrix metalloproteinase-3 (MMP-3) <103.7 ng/ml at outset predicts a patient subgroup that exhibits no radiographic progression. Conclusions: Half of rheumatoid patients treated with MTX monotherapy for 3 years exhibited structural remission, and this outcome can be predicted at the outset by lower serum MMP-3.

AB - Background: The study was undertaken to assess the efficacy of methotrexate (MTX) monotherapy on the radiographic progression of individual rheumatoid arthritis (RA) patients, each of whom had received MTX monotherapy for 3 years with an option to change to biological disease-modifying anti-rheumatic drugs (bDMARDs). We also looked for predictors of radiographic non-progression in these patients. Methods: Rheumatoid patients (n = 161) were prospectively followed for 3 years while receiving low-dose MTX monotherapy unless disease was otherwise active and/or adverse events appeared. Their disease activity and radiographic progression were evaluated with reference to disease activity score 28 (DAS28), modified health assessment of questionnaire (mHAQ) and other indices. The change in van der Heijde-modified total Sharp score per year (TSS) was assessed using probability plots, in which the patients were classified into the subgroups showing structural remission (REM; TSS ≤0.5), radiographic progression (TSS >3) or rapid radiographic progression (RRP; TSS >5). Results: MTX monotherapy, continued until disease became active and/or adverse event appeared, was associated with a significant improvement (p <0.0001) in the DAS28-ESR (3) scores, % DAS28 remission, and mHAQ scores each year, from baseline to 3 years. The mHAQ remission rate (mHAQ <0.5) and Boolean remission were also improved from 16 to 60 % and 0.8 to 24.0 %, respectively. We found that the ratio of patients classified as REM increased yearly from 62/161 (38.5 %) to 69/137 (50.4 %), while those classified as TSS >3 decreased from 55/161 (34.2 %) to 28/137 (20.4 %) and those in RRP decreased from 35/161 (21.7 %) to 15/137 (10.9 %). Receiver operating characteristic (ROC) curve analyses showed that serum matrix metalloproteinase-3 (MMP-3) <103.7 ng/ml at outset predicts a patient subgroup that exhibits no radiographic progression. Conclusions: Half of rheumatoid patients treated with MTX monotherapy for 3 years exhibited structural remission, and this outcome can be predicted at the outset by lower serum MMP-3.

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