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AB0447 Regulation of Serum Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases-1 following Rituximab Therapy in Patients with Rheumatoid Arthritis Refractory to Anti-Tumor Necrosis Factor Blockers
  1. P.A. Klimiuk,
  2. I. Domyslawska,
  3. S. Sierakowski,
  4. J. Chwiecko
  1. Department of Rheumatology and Internal Diseases, Medical University of Bialystok, Bialystok, Poland

Abstract

Background Serum matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play important role in the pathogenesis of rheumatoid arthritis (RA).

Objectives In our article we evaluated the regulatory effects of the infusions of rituximab, a monoclonal antibody directed against CD20+ B cells, on the serum MMPs and TIMP-1 levels in patients with active RA not responding to anti-tumor necrosis factor (anti-TNF) therapy.

Methods Twelve RA patients were planned to receive 4 infusions of 1000mg of rituximab at weeks 0, 2, 24, and 26. The therapy was combined with methotrexate (MTX) (20-30mg/week). Seven patients were refractory to previously received infliximab, and 5 to etanercept. Serum concentrations of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9) and TIMP-1 were measured by ELISA on weeks 0, 2, 12, 24, 36 and 52.

Results Initial infusion of rituximab down-regulated serum MMP-1 (p<0.01), MMP-3 (p<0.001), MMP-9 (p<0.001) and TIMP-1 (p<0.05) levels. Second drug administration caused even more remarkable reduction of measured MMPs (p<0.001 in all cases) and TIMP-1 level (p<0.01). These findings were accompanied by significantly decreased ratios of measured MMPs to TIMP-1. Next rituximab infusions on weeks 24 and 26 sustained the suppression of serum MMPs levels. Prior to the initial rituximab infusion serum concentrations of studied MMPs and TIMP-1 significantly correlated with markers of RA activity such as disease activity score (DAS28) and CRP levels.

Conclusions Rituximab therapy, beside a rapid clinical improvement, reduced serum MMPs concentrations in RA patients refractory to anti-TNF treatment. Repeated infusions of rituximab maintained initial serum MMPs suppression.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.1496

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