Objectives To evaluate a relationship between the level of matrix metalloproteinase-3 (MMP-3) with disease activity and clinical efficacy of subcutaneous methotrexate (SC-MTX) in early DMARD -naive rheumatoid arthritis (RA) patients (pts)
Methods Serum samples of 45 early RA DMARD-naive pts (35 females, median age 53.5; interquartile range 46-59.5 years, disease duration 7.0;4.0-11.5 months, DAS 28 5.8;4.9-6.4, RF positive-91%, anti-CCP positive-96%) were analyzed for the levels of MMP-3 before and after 12 and 24 weeks of treatment. In all pts SC-MTX monotherapy was started from 10 mg weekly and escalated to 20–25 mg weekly in the next 2-3 weeks. Pts were assessed every 12 weeks and if a remission was not achieved, biologic therapy was added. The duration of the study was 1 year. In the sera samples of 30 healthy donors MMP-3 levels were lower than 19.4 ng/ml (measured by ELISA)
Results After 12 months 16 pts (35.6%), DAS 28 1.7;1.6-4.1, had received SC-MTX monotherapy. In 29 active RA pts (64.4%), DAS 28 3.1;1.9-4.3 biologic therapy was added (82% adalimumab, 13% abatacept, and 5% other agents).
MMP-3 levels in RA pts were higher than in healthy donors: 46.7;15.5-64.5 – and 7.74; 5.5-11.8, respectively, p<0.05. Elevated MMP-3 levels were observed in 64.4% of pts. These pts had both higher disease activity and erosion score as compared to pts with normal MMP-3 levels (Table1)
At week 12 and 24, MMP-3 decreased in SC-MTX monotherapy group: 23.7 (1.5-44.5) and 0.025 (0.025-29.0), p<0.05 for both cases; in SC-MTX and biologic therapy group: 31.7 (16.3-72.0) and 7.0 (0.03-29.0), respectively, p<0.05 for both cases, as compared to baseline.
At baseline, low disease activity (DAS 28 4.4;4.4-5.7, SDAI 24.1;16.9-35.7, CDAI 20.7;15.8-30.0) and low MMP-3 levels (10.6;0.03-38.1) were observed in SC-MTX monotherapy group (n=16) compared with SC-MTX plus biologic therapy group (n=29) (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 for all cases.
After ROC analysis we found that elevated MMP-3 levels at baseline (>54.6) and week 12 (>25.1) were associated with the lack of SC-MTX efficacy at 48 weeks of the observation (AUC 0,78 95% CI 0,63-0,93 and AUC 0,96 95% CI 0,54-0,86, respectively) Fig.1, 2.
Conclusions High MMP-3 level at baseline and after 12 weeks of SC-MTX monotherapy could be considered as a possible predictor of a poor response of SC-MTX treatment
Disclosure of Interest None declared
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