Recently, the treatment of rheumatoid arthritis has advanced rapidly because of the appearance of the biologics reagents. Although almost 70% of the treated patients respond to these therapies, these agents are expensive and sometimes cause side effects. For unknown reasons, 30–40% of RA patients do not respond well to these biologics reagents. Therefore, it is possible to administer it to an effective example at the time of beginning if effectiveness can be predictive before treatment.
The ADAMTS(a disintegrin and metalloproteinase with thrombospondin motifs) family molecules, which has the structural homology with MMP(matrix metalloprotease) family molecules and ADAM(a disintegrin and metalloproteinase) family molecules, have been reported to play a key role in aggrecan degradation in cartilage. To identify a biomarker for prediction of the response to biologics, ex, infliximab (IFX), etanercept (ETN), adalimumab (ADA), tocilizumab (TCZ), or abatacept (ABA), we focused on ADAMTS5, because ADAMTS5 has been shown to have the ability to destroy cartilage through degradation of aggrecan, independently of tumor necrosis factor α (TNFα). First of all, peripheral blood was collected using PAX gene tubes before treatment, and total RNA was extracted and cDNA was isolated using RT. Relative amount of the baseline ADAMTS5 mRNA was quantified using real-time PCR compared with the amount of β actin mRNA.
As a result, we discovered that IFX and ETN are effective when the baseline ADAMTS5 mRNA expression is low in the peripheral blood (PCT International Publication No. WO/2010/038840, US application No. 13/075,490). On the other hand, ADA is effective when the baseline ADAMTS5 mRNA expression is high (PCT International Publication No. WO/2011/065168). We also discovered that TCZ and ABA are effective when the baseline ADAMTS5 mRNA expression is up-regulated. We developed the diagnostic procedure of the biologics therapy using this gene. The mechanism of ADAMTS5 to predict the efficacy of the biologics is here.