Cartilage turnover markers are predictive of ACR70 response to anti-TNF alfa treatment in RA-patients

Background: Rheumatoid arthritis (RA) has a variable course with a wide range of potential outcomes, making it difficult to predict disease progression and magnitude of therapeutic response. The possibility to identify rapid versus slow responders at an early stage, has the potential to improve the care of the patients Objectives: To investigate in RA patients the possibility to apply a combination of markers reflecting different basic disease mechanisms to improve ability to predict rapid and sustained clinical response to anti-TFN treatment. Methods: 81 out of 85 consecutive RA patients were monitored in accordance with a structured protocol during three different anti-TNF therapies and were tested for serum Cartilage Oligomeric Matrix Protein (COMP) and C-Reactive protein (CRP) at baseline. 35 pts were treated with Adalimumab, 30 with Infliximab and 20 with Etanercept (4 serum samples were excluded because of incomplete data). The response to the therapy was evaluated by ACR20,50, 70. CRP was used to describe systemic inflammation and COMP to describe cartilage turnover. Levels of COMP were tested by using a commercial sandwich immunoassay (AnaMar Medical, Sweden) and levels below 10 U/L were considered as low cartilage turnover. CRP levels exceeding 10 ug/ml were considered as elevated. The outcome of the two markers was combined to investigate a possible synergy between the markers. Results: We could not find any difference in ACR20 between the two groups with low or elevated baseline COMP levels, at any time points. However, the percentage of ACR70 responders was significantly (p<0.005) higher in the group of patients with low COMP levels, at 3 months follow up. The percentage of ACR70 responders did not increase at 6 months for patients with low COMP at baseline in contrast to the patients with higher COMP. At 12 months there was no differences between the two groups. The percentage of ACR 70 responders in the group with normal cartilage turnover was high (38% at three months) but did not increase over time, in contrast to the group with elevated cartilage turnover that significantly (p<0.05) increased the percentage of ACR 70 response over time. The patient groups did not differ significantly in disease activity at baseline. Table 1. Comparison of percentage of ACR 70 responders at 3 months, at 6 months, at 12 months, in groups selected at baseline status of in vitro tests Group 3 months 6 months 12 months Mean value all patients (n=81) 20% 24% 31% COMP Normal (basal) (n=26) 38% ** 35% 42% COMP Elevated (basal) (n=55) 11% 18%* 27%* P-values are indicated by * for p<0.05 and ** for p<0.005 and shows the significance between groups with normal and elevated marker levels Conclusion: The results of the study suggest that the outcome of COMP may be helpful to the treating physician when considering continued observation or modification of the current treatment. References: G. Morozzi, F. Bellisai, M. Fabbroni, S. Cucini, M. R. Bacarelli, M. Galeazzi: Levels of circulating COMP and anti-CCP in RA patients treated with adalimumab: Ann Rheum Dis 2005; 64: 103