Soshi Takahashi1,2, Jun Saegusa1, Akira Onishi1, Akio Morinobu1. 1. Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine, Kobe,Japan. 2. Centre for Rheumatic Disease, Shinko Hospital, Kobe,Japan.
Abstract
OBJECTIVES: Biologic treatment has recently revolutionized the management of RA. Despite this success, ∼30-40% of the patients undergoing biologic treatment respond insufficiently. The aim of this study was to identify several specific reliable metabolites for predicting the response of RA patients to TNF-α inhibitors (TNFi) and abatacept (ABT), using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS). METHODS: We collected serum from RA patients with moderate or high disease activity prior to biologic treatment, and obtained the serum metabolomic profiles of these samples using CE-TOFMS. The patients' response was determined 12 weeks after starting biologic treatment, according to the EULAR response criteria. We compared the metabolites between the response and non-response patient groups and analysed their discriminative ability. RESULTS: Among 43 total patients, 14 of 26 patients in the TNFi group and 6 of 17 patients in the ABT group responded to the biologic treatment. Of the metabolites separated by CE-TOFMS, 196 were identified as known substances. Using an orthogonal partial least-squares discriminant analysis, we identified five metabolites as potential predictors of TNFi responders and three as predictors of ABT responders. Receiver operating characteristic analyses for multiple biomarkers revealed an area under the curve (AUC) of 0.941, with a sensitivity of 85.7% and specificity of 100% for TNFi, and an AUC of 0.985, with a sensitivity of 100% and specificity of 90.9% for ABT. CONCLUSION: By metabolomic analysis, we identified serum biomarkers that have a high ability to predict the response of RA patients to TNFi or ABT treatment.
OBJECTIVES: Biologic treatment has recently revolutionized the management of RA. Despite this success, ∼30-40% of the patients undergoing biologic treatment respond insufficiently. The aim of this study was to identify several specific reliable metabolites for predicting the response of RApatients to TNF-α inhibitors (TNFi) and abatacept (ABT), using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS). METHODS: We collected serum from RApatients with moderate or high disease activity prior to biologic treatment, and obtained the serum metabolomic profiles of these samples using CE-TOFMS. The patients' response was determined 12 weeks after starting biologic treatment, according to the EULAR response criteria. We compared the metabolites between the response and non-response patient groups and analysed their discriminative ability. RESULTS: Among 43 total patients, 14 of 26 patients in the TNFi group and 6 of 17 patients in the ABT group responded to the biologic treatment. Of the metabolites separated by CE-TOFMS, 196 were identified as known substances. Using an orthogonal partial least-squares discriminant analysis, we identified five metabolites as potential predictors of TNFi responders and three as predictors of ABT responders. Receiver operating characteristic analyses for multiple biomarkers revealed an area under the curve (AUC) of 0.941, with a sensitivity of 85.7% and specificity of 100% for TNFi, and an AUC of 0.985, with a sensitivity of 100% and specificity of 90.9% for ABT. CONCLUSION: By metabolomic analysis, we identified serum biomarkers that have a high ability to predict the response of RApatients to TNFi or ABT treatment.
Authors: Jessica D Murillo-Saich; Cesar Diaz-Torne; M Angeles Ortiz; Roxana Coras; Paulo Gil-Alabarse; Anders Pedersen; Hector Corominas; Silvia Vidal; Monica Guma Journal: Metabolomics Date: 2021-08-16 Impact factor: 4.747
Authors: Helen R Gosselt; Ittai B Muller; Gerrit Jansen; Michel van Weeghel; Frédéric M Vaz; Johanna M W Hazes; Sandra G Heil; Robert de Jonge Journal: J Pers Med Date: 2020-12-10
Authors: Clara Depommier; Amandine Everard; Céline Druart; Dominique Maiter; Jean-Paul Thissen; Audrey Loumaye; Michel P Hermans; Nathalie M Delzenne; Willem M de Vos; Patrice D Cani Journal: Gut Microbes Date: 2021 Jan-Dec