Why ADAMTS5 could predict the efficacy of biologics?

  We have already reported that infliximab (IFX) would be effective (DAS remission) if the baseline blood ADAMTS5 mRNA was below 1.2 Index while adalimumab (ADA) would be effective if it was more than 1.7 Index. However, there observed one major question that how we can explain the different pattern of baseline ADAMTS5 to predict between these two biologic reagents against the same TNFα.

  We have recently discovered the answer to the above question and the mechanism of the prediction using baseline blood ADAMTS5. ADAMTS5 is one of the metalloproteinase. RA patients with high level of blood ADAMTS5 have been reported to demonstrate severe cartilage destruction. We investigated the relationship between ADAMTS5 and autoantibodies, especially rheumatoid factor (Rf). From the observations, the frequency of serum Rf in ADA-treated RA patients with low level (1.7 Index) of baseline blood ADAMTS5 mRNA (83%) was significantly (p<0.001) higher than those (50%) with high level (> 1.7 Index) of ADAMTS5 patients, suggesting the low influence of cartilage destruction but ADA failure due to Rf, poor prognosis factor in low-level of ADAMTS5 RA patients (Fig.). On the other hand, as the frequency of serum Rf was not different between IFX-treated RA patients with low (1.2 Index) ADAMTS5 level and high (> 1.2 Index) ADAMTS5 level, RA patients with high-level of ADAMTS5 should be IFX failure due to the cartilage destruction (Fig.). This inverse proportion between ADAMTS5 and Rf has been confirmed between ADAMTS4 and Rf or MMP-3 and Rf as well. Therefore, the efficacy prediction using baseline blood ADAMTS5 level might be determined by two components, cartilage destruction and autoantibodies like Rf. We are now investigating these relationships in RA patients treated with etanercept, tocilizumab, and abatacept.

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