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Effect of repeated infliximab therapy on serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with rheumatoid arthritis
OBJECTIVE: Matrix metalloproteinases (MMP) are involved in the articular tissue destruction processes in the pathogenesis of rheumatoid arthritis (RA). We investigated the effects of multiple infusions of infliximab, a chimeric anti-tumor necrosis factor-a (anti-TNF-a) antibody, on concentrations of...
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Published in: | Journal of rheumatology 2004-02, Vol.31 (2), p.238-242 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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Summary: | OBJECTIVE: Matrix metalloproteinases (MMP) are involved in the articular tissue destruction processes in the pathogenesis
of rheumatoid arthritis (RA). We investigated the effects of multiple infusions of infliximab, a chimeric anti-tumor necrosis
factor-a (anti-TNF-a) antibody, on concentrations of serum MMP and tissue inhibitors of metalloproteinases (TIMP) in patients
with active RA. METHODS: Patients with RA were scheduled to receive 9 infusions of infliximab (3 mg/kg) at Weeks 0, 2, 6,
and every 8 weeks thereafter. The therapy was combined with methotrexate (MTX) (7.5-20 mg/week). Serum concentrations of interstitial
collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9), TIMP-1, and TIMP-2 were measured by ELISA prior to infusion
at Weeks 0, 2, 6, 14, 38, and 62. RESULTS: The initial infusion of infliximab downregulated serum levels of MMP-1 (p < 0.001),
MMP-3 (p < 0.001), MMP-9 (p < 0.001), TIMP-1 (p < 0.01), and TIMP-2 (p < 0.05). The second drug administration caused even
more remarkable reduction of measured MMP (p < 0.001 in all cases) but not of TIMP levels. These changes were accompanied
by decreased ratios of measured MMP to TIMP. Further infliximab therapy also significantly suppressed serum MMP levels, but
was less effective. Before the first infliximab infusion serum concentrations of MMP and TIMP correlated with markers of RA
activity such as the Disease Activity Score and C-reactive protein levels. After further drug administrations such associations,
although less significant, were also noted. CONCLUSION: Anti-TNF-a antibody therapy combined with MTX resulted in rapid clinical
improvement and reduced serum MMP concentrations in patients with RA. Further infusions of infliximab maintained the decrease
of MMP, although to a lesser extent than the first and second doses. |
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ISSN: | 0315-162X 1499-2752 |