J Rheum Dis.  2022 Apr;29(2):89-97. 10.4078/jrd.2022.29.2.89.

Evaluation of Serum Matrix Metalloproteinase-3 as an Objective Indicator for the Disease Activity in Rheumatoid Arthritis Patients Treated With Methotrexate Versus Tocilizumab: 24-week Results From a Prospective Randomized Controlled Study

• Yeo J
• Baek HJ
• Song YW
• Lee EY

• KMID: 2527548
• DOI: http://doi.org/10.4078/jrd.2022.29.2.89

Abstract

Objective
This study aims to evaluate the change in serum metalloproteinase-3 (MMP-3) following the management of active rheumatoid arthritis (RA) and define the relationships between MMP-3 and disease activity indices.
Methods
Data from a previously reported a 24-week, randomized controlled trial to investigate efficacy of tocilizumab in active RA refractory to methotrexate were analyzed. The serum level of MMP-3 were measured at week 0, 12, 20, and 24. The changes in MMP-3, and the relationship between MMP-3 and clinical parameters was assessed based on treatment group, methotrexate with or without tocilizumab.
Results
A total of 95 patients were included in this study. The serum MMP-3 significantly decreased and showed similar pattern with other disease activity indices during treatment period in both treatment groups (p<0.001). The MMP-3 was positively correlated with ESR, CRP, DAS28, SDAI, and CDAI for 302 visits throughout 24 weeks (p<0.001). In another correlation analysis to evaluate the treatment effect at 24 week time point, methotrexate group showed significant correlation between serum markers: MMP-3 (r=0.321, p=0.043); ESR (r=0.450, p=0.002); and CRP (r=0.536, p<0.001), with DAS28, but tocilizumab group didn’t show meaningful correlation between serum markers and DAS28 (p>0.05).
Conclusion
Serum MMP-3 showed positive correlation with disease activity indices in active RA patients. Furthermore, serum MMP-3 significantly decreased from baseline to week 20. As there is no single serum marker that can represent the disease activity particularly in tocilizumab treatment, MMP-3 might be a useful adjunct indicator to evaluate the treatment response in active RA patients.

Keyword

Matrix metalloproteinase 3; Rheumatoid arthritis; Biomarker; Methotrexate; Tocilizumab

Figure

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  Fig. 1 Changes in level of serum MMP-3 (A) and disease activity indices (B~F) between two treatment groups during 24-week follow up. Statistical analysis was performed by linear mixed model adjusted for age, sex, and treatment. Data were expressed as mean (SE) value. CDAI: Clinical Disease Activity Index, CRP: C-reactive protein, DAS28: 28-joint Disease Activity Score, ESR: erythrocyte sedimentation rate, MMP-3: metalloproteinase-3, MTX: methotrexate, SDAI: Simplified Disease Activity Index, SE: standard error, TCZ: tocilizumab.

• 

  Fig. 2 Correlation of each serum marker with DAS28 at 24 weeks. Pearson’s correlation coefficient (r) and p-value levels are decribed. DAS28: 28-joint Disease Activity Score, ESR: erythrocyte sedimentation rate, MMP-3: metalloproteinase-3, MTX: methotrexate, TCZ: tocilizumab.

• 

  Fig. 3 Changes in serum MMP-3 (A), ESR (B), and CRP (C) levels across the 24 weeks according to two disease activity groups. Statistical analysis was performed by performed by linear mixed model adjusted for age, sex, and treatment. Data were expressed as mean (SE) value. Non HDA at 24 weeks; non high disease activity group including patients with remission, low and moderate disease activity at 24 weeks, DAS28≤5.1. HDA at 24 weeks; high disease activity group at 24 weeks, DAS28>5.1. DAS28: 28-joint Disease Activity Score, CRP: C-reactive protein, ESR: erythrocyte sedimentation rate, MMP-3: metalloproteinase-3, RA: rheumatoid arthritis, SE: standard error.

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