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

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.