Metabolomics Profling Predicts Outcome Of Tocilizumab In Rheumatoid Arthritis

Objective: Rheumatoid arthritis(RA)is a chronic autoimmune disease manifested by synovitis,bone erosion and bone destruction.Currently,the main treatment is to use drugs to relieve the disease,and there is no biological marker that can accurately predict the efficacy of drugs in clinic.With the development of high-throughput technology and multi-omics,some promising biomarkers for diagnosing and treating RA have been discovered.Tocilizumab,a humanized antibody against of human IL-6 receptor,is often used clinically to treat RA,and there are still some patients with RA who show poor efficacy when treated with TCZ.In order to fully understand the efficacy of TCZ,further exploration of biological markers provided by TCZ is meaningful.Methods: Sixty patients with active RA who received TCZ treatment in Sichuan Provincial People’s Hospital were included.Blood samples and related data of patients at baseline were collected.Patients were assessed after six months of treatment to determine clinical outcomes and were divided into three groups,good-response,moderate-response,and none-response.Metabolite quantification and qualitative analysis of blood samples were performed by LC-MS,and the results were used for statistical and pathway analysis.Results: In this experiment,there are significant differences between different groups.72 meaningful differential metabolites were detected in the three groups.ROC curve analysis suggests that niacinamide may have promised results for predicting the response of TCZ to RA.Combining the niacinamide,malathion monocarboxylic acid,methylsuccinic acid,and glycylphenylalanylleucylglycine ROC analysis can improve the accuracy of prediction of TCZ response in RA patients.The KEGG pathway enrichment analysis results showed that the main enriched signaling pathways were the c AMP signaling pathway,glycerophospholipid metabolism pathway,and phenylalanine metabolism pathway.Conclusion: This thesis showed that plasma differential metabolites have some values in predicting the response of TCZ to RA.Among these differential metabolites,the marker set composed of niacinamide,malathion monocarboxylic acid,methylsuccinic acid,and glycylphenylalanylleucylglycine has high accuracy in predicting the response of TCZ to RA.