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SAT0218 Association of Matrix Metalloproteinase-3 Level with Clinical Efficacy of Subcutaneous Methotrexate in Dmard -Naive Patients with Early Rheumatoid Arthritis
  1. A.S. Avdeeva,
  2. E.N. Aleksandrova,
  3. D.E. Karateev,
  4. E.L. Luchikhina,
  5. A.V. Smirnov,
  6. A.A. Novikov,
  7. M.V. Cherkasova,
  8. E.L. Nasonov
  1. Nasonova Research Institute of Rheumatology, Moscow, Russian Federation

Abstract

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)

Table 1

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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