Disease activity and treatment response in early rheumatoid arthritis: an exploratory metabolomic profiling in the NORD-STAR cohort

作者：Tahzeeb Fatima, Yuan Zhang, Georgios K. Vasileiadis, Araz Rawshani, Ronald van Vollenhoven, Jon Lampa, Björn Guðbjörnsson, Espen A. Haavardsholm, Dan Nordström, Gerður Gröndal, Kim Hørslev‐Petersen, Kristina Lend, Marte Schrumpf Heiberg, Merete Lund Hetland, Michael T. Nurmohamed, Mikkel Østergaard, Till Uhlig, Tuulikki Sokka, Anna Rudin, Cristina Maglio · 发表于：Arthritis Research & Therapy · 年份：2025 · DOI：10.1186/s13075-025-03616-6 · 被引用次数：7 · 研究领域：Rheumatoid Arthritis Research and Therapies、Metabolomics and Mass Spectrometry Studies、Traditional Chinese Medicine Studies

BACKGROUND: The variability in treatment response in people with rheumatoid arthritis (RA) warrants the prediction of patients at high risk of treatment failure. Identification of biomarkers linked to clinical remission in RA is currently a challenge. Metabolomics may help to identify such biomarkers as it allows for a comprehensive exploration of disease-related variations that extends beyond the genome and proteome. This hypothesis-free exploratory metabolomics study aimed to profile serum metabolic alterations in early RA to understand the metabolic changes associated with disease activity and therapeutic response. METHODS: The study included 220 early RA participants from the NORD-STAR study, randomized at baseline into four arms, ranging from conventional anti-rheumatic treatment to biological drugs: methotrexate combined with prednisolone (1), certolizumab (2), abatacept (3), or tocilizumab (4). Untargeted metabolomics was performed in serum samples at baseline and 24-week follow-up. Participants achieving clinical disease activity index remission at 24 weeks were defined as responders. Machine learning models for treatment response were constructed using random forest, logistic regression, support vector machine and extreme gradient boosting algorithms based on selected features. RESULTS: We identified 278 metabolites, of which 39 were associated with baseline disease activity, including several acylcarnitines and amino acids. We also found 17 baseline metabolites asso...