Session Type: Abstract Submissions (ACR)
Background/Purpose :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. In this study, we examined ADAM-10 as a predictive treatment factor 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 disease activity score 28 (DAS28). 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 compared between responders and nonresponders.
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 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). 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).
Conclusion :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.
Abbott Immunology Pharmaceuticals,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/adam-10-as-a-tocilizumab-treatment-predictive-factor-in-rheumatoid-arthritis/