Background A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) has been reported to play a key role in aggrecan degradation in cartilage. Lower level of the baseline blood ADAMTS5 mRNA level has been also reported to predict the better response to infliximab (IFX) in RA patients using a single-center study.
Objectives In this study, we performed a prospective, multicenter, and observational study to derive and validate the baseline blood ADAMTS5 mRNA that would be predictive of the efficacy of IFX in RA patients.
Methods Forty-one RA patients (Age, 54.1±12.3 y/o; Disease duration, 4.5±7.1 years; DAS28_ESR, 5.07±1.07; SDAI 23.5±1.03; Bio naïve, 91.7%) were enrolled and treated with IFX. Peripheral blood samples were collected at baseline and ADAMTS5 mRNA was quantified using real-time PCR as the ratio of b-actin mRNA (Index as BiologicMate®).
Results Five patients dropped out of this study while 44.1%, 14.7%, 29.4%, 41.1%, 23.5%, and 23.5% of the remaining patients achieved good responder, none responder, DAS_ESR remission, DAS_CRP remission, SDAI remission, and Boolean remission at 14 weeks' treatment with IFX, respectively. Baseline ADAMTS5 mRNA levels in the SDAI remission group was significantly (p=0.049) lower than that in the non-SDAI remission group at 14 weeks' treatment with IFX. Area under curve (AUC) of the ROC curve for predicting the SDAI remission (SDAI ≤3.3) using the baseline ADAMTS5 mRNA at 14 weeks was 0.67, and the cut-off value of ADAMTS5 mRNA was calculated as 2.1 Index. There observed no difference in the general patient backgrounds (average age, disease duration, dose of MTX, dose of steroid, baseline SDAI, etc) between Low-ADAMTS5 (<2.1 Index) group and High-ADAMTS5d group. However, DAS28, CDAI, and SDAI at 14 weeks after treatment were significantly (p=0.031) lower in Low-ADAMTS5 group than those in High-ADAMTS5 group. The accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the baseline Low-ADAMTS5 (<2.1 Index) for predicting the SDAI remission (SDAI ≤3.3) at 14 weeks after treatment with IFX were 76.5%, 66.7%, and 85.7%, respectively. Interestingly, we observed positive correlation between baseline ADAMTS5 mRNA and SDAI score at 14 weeks after treatment with IFX.
Conclusions The baseline blood ADAMTS5 mRNA level was validated as a biomarker for the prediction of the response to IFX in RA patients using the multicenter clinical trial.
Disclosure of Interest K. Tsuzaka Shareholder of: Kaytee Bio, Co.&Ltd., M. Nagata: None declared, K. Amano: None declared, T. Mimura: None declared, S. Kagami: None declared, Y. Miwa: None declared, K. Ikeda: None declared, T. Mitsuka: None declared, H. Kanai: None declared, I. Sekigawa: None declared