[Relationship of the clinical efficiency of tocilizumab therapy to the serum level of matrix metalloproteinase-3 in patients with rheumatoid arthritis]

A S Avdeeva, E N Aleksandrova, A A Novikov, M V Cherkasova, E Yu Panasyuk, E L Nasonov
Terapevticheskiĭ Arkhiv 2013, 85 (5): 24-9

AIM: To evaluate the impact of tocilizumab (TCZ) therapy on the level of matrix metalloproteinase-3 (MMP-3) 4, 24, and 48 weeks after treatment initiation in relation to the clinical efficiency of TCZ therapy by the Disease Activity Score (DAS28), the Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI).

SUBJECTS AND METHODS: Forty-two rheumatoid arthritis (RA) patients who had received 6 intravenous infusions of TCZ 8 mg/kg at a 4-week interval during permanent therapy with disease-modifying anti-rheumatic drugs (DMARD) and glucocorticosteroids (GCS) were examined. Then TCZ was discontinued and the patients continued to receive the previous therapy with DMARD and GCS. The European League Against Rheumatism (EULAR) classification criteria, as well as SDAI and CDAI were used to evaluate the efficiency of TCZ therapy. The serum concentration of MMP-3 was measured by enzyme immunoassay using the test systems (Invitrogen, USA).

RESULTS: After 24 weeks of TCZ therapy (at 48 weeks following trial initiation), DAS28 was 4.69 (3.86; 5.44); the SDAI of 17.8 (10.7; 29.5) and the CDAI of 17.1 (7.2; 26.2) corresponded to moderate disease activity. At 48 weeks, DAS28 remission (< 2.6 scores) remained in 5 (11.90%) patients; SDAI (< or = 3.3 scores) and CDAI (< or = 2.8 scores) remissions did in 3 (7.1%) and 4 (9.5%) patients, respectively. There was a significant reduction in MMP-3 concentrations at 4, 24, and 48 weeks of the therapy, which was 61, 73, and 49.40% of the baseline level. ROC analysis indicated that the normalization of MMP-3 levels in RA patients at 24 weeks of TCZ therapy (a cut-off < or =16.5 ng/ml) was associated with the maintenance of remission/low disease activity from SDAI and CDAI 24 weeks after the drug use (the area under the receiver operating curve was 0.762; 95% confidence interval: 0.548-0.976).

CONCLUSION: Analysis of the results of 48-week TCZ therapy suggests its ability to reduce the levels of markers of bone and cartilage destruction in patients with RA. Serum MMP-3 determination at 24 weeks of therapy may be useful in predicting the maintenance of remission/low activity from SDAI and CDAI after discontinuation of the drug.


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