ROLE OF MATRIX METALLOPROTEINASE 3 IN PREDICTING THE EFFICIENCY OF THERAPY FOR EARLY RHEUMATOID ARTHRITIS: THE REMARCA TRIAL

Objective: to investigate the impact of treatment with subcutaneous methotrexate (MTX) and combined therapy with MTX and biological agents (BA) on the serum level of matrix metalloproteinase 3 (MMP3); to estimate the informative value of determination of MMP3 levels for predicting the clinical efficiency of therapy for early rheumatoid arthritis (RA).

Subjects and methods. A total of 45 patients with early RA were examined. In all the patients, MTX as the first disease-modifying anti-rheumatic drug was subcutaneously injected at a dose of 10 mg/week with its rapid escalation up to 20–25 mg/week. When the efficacy of MTX was inadequate, a BA was added [82% of the patients received adalimumab, 13% – abatacept, and 5% – other BA]; the follow-up duration was 1 year. Serum MMP3 levels were measured using an enzyme immunoassay before, 12 and 24 weeks after initiation of therapy.

Results and discussion. After week 52 16 patients continued to receive monotherapy with subcutaneous MTX; BA were added to therapy in 29 patients in different follow-up periods. In the patients with early RA, the baseline MMP3 level was significantly higher than that in healthy donors: 46.7 [15.5; 64.5] and 7.74 [5.5; 11.8] respectively (p < 0.05). In the entire group, the level of MMP3 significantly declined after 12 and 24 weeks of therapy when it was 23.7 [1.5; 44.5] and 3.25 [0.025; 29.0], respectively. 16 patients who responded well to MTX after 52 weeks of therapy showed lower baseline inflammatory activity: (DAS28, 4.4 [4.4; 5.7], SDAI, 24.1 [16.9; 35.7], and CDAI, 20.7 [15.8; 30.0]) and MMP3 levels (10.6 [0.03; 38.1]) than those in 29 patients receiving the combined therapy: 6.05 [5.3; 6.7], 40.7 [26.7; 48.2], 35.8 [23.5; 42.8], and 58.8 [27.0; 106.3], respectively (p < 0.05). ROC analysis established that the baseline MMP3 level of > 54.6 ng/ml and the persistent higher level of this parameter 12 weeks after the initiation of treatment with MTX (> 25.1 ng/ml) were associated with lack of efficiency of MTX monotherapy after 52 weeks and with the necessity of using combined therapy [area under the curve (AUC), 0.78; 95% confidence interval (CI), 0.63–0.93 and AUC, 0.96; 95% CI, 0.54–0.86, respectively].

Conclusion. The high baseline MMP3 level (> 54.6 ng/ml) and the persistent increased level of this parameter 12 weeks after initiation of therapy with subcutaneous MTX (> 25.1 ng/ml) may be regarded as a likely predictor for the inefficiency of MTX monotherapy and for the necessity of using BA.

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