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THU0064 ADAM-10 as a tocilizumab treatment predictive factor in rheumatoid arthritis
  1. T Isozaki,
  2. S Nishimi,
  3. A Nishimi,
  4. S Ishii,
  5. T Tokunaga,
  6. H Furuya,
  7. K Wakabayashi,
  8. T Kasama
  1. Division of Rheumatology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan

Abstract

Background A disintegrin and metalloproteinases (ADAMs) are a family of transmembrane and secreted proteins. ADAM-10 has been reported to be the enzyme responsible for the release of a number of chemokines and cytokine receptors. We have shown that ADAM-10 is overexpressed on rheumatoid arthritis (RA) synovial tissue endothelial cells (ECs) and lining cells compared with osteoarthritis and normal tissues. We also demonstrated that ADAM-10 mediates EC migration and tube formed.

Objectives In order to demonstrate for ADAM-10 in clinical side, we focused on ADAM-10 as predictive factor for treatment with biologics in RA.

Methods The serum was collected from patients before the initial treatment with biological therapies. Fifteen patients were treated with adalimumab (ADA), and 20 patents were treated with tocilizumab (TCZ). ADAM-10 and fractalkine/CX3CL1 were measured by enzyme-linked immunosorbent assay at 0, 12, 24 and 54 weeks. Clinical disease activity was evaluated by clinical disease activity index (CDAI). Following biological therapies, we defined biologic-responders as patients whose DAS28 scores decreased by more than 1.2 at 24 weeks. ADAM-10 baseline was also compared between responders and nonresponders at 24 weeks.

Results There were no significant differences were observed in the mean age, gender ratio, dosages of predonisolone and methotraxate between ADA and TCZ groups. In ADA group, baseline DAS28 for the 15 patients was 4.8±0.3 (2.5–7.2). On the other hands, baseline DAS28 for the 20 patients was 4.8±0.3 (2.5–6.8) in TCZ group. There were no differences between ADA and TCZ groups. RA patients with an insufficient response to ADA or TCZ showed highly significant improvement of DAS28 after 12 weeks (2.9±0.3 and 2.2±0.4, respectively), and 24 weeks (2.5±0.4 to 2.2±0.2, respectively). ADAM-10 highly correlates with CDAI, and fractalkine/CX3CL1. Serum ADAM-10 levels were no remarkable change after treatment with ADA despite decrease of disease activity of RA. On the other hand, serum ADAM-10 levels in patients who were treated with TCZ were significantly diminished following successful treatment and clinical improvement (baseline 408±88 pg/ml and 54 weeks 138±51 pg/ml, p<0.05). Univariate logistic regression analysis, baseline of DAS28 (ESR), baseline of CDAI, and ADAM-10 were selected as significant variables for improvement of DAS28 (ESR) at 24 weeks. Multiple regression analysis showed that ADAM-10 was only identified as independent predictive variable for improvement of DAS28 (ESR) at 24 weeks. ADAM-10 baseline in TCZ responder was significantly higher than TCZ nonresponders at 24 weeks (620±134 pg/ml and 109±25 pg/ml, respectively, p<0.05).

Conclusions This study indicates that ADAM-10 is correlated with RA disease activity, and is higher in TCZ responders. These results suggest that ADAM-10 may be a predictor of treatment effectiveness for RA with TCZ.

Disclosure of Interest None declared

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