Evidence map›Paper›PMID 40801465›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

A Longitudinal Study Reveals Metabolomic Markers for Individuals at Risk, Disease Severity, and Treatment Response in Rheumatoid Arthritis.

Chenxi Zhu, Jiayi Xu, Siyu He, Qian Niu, Yi Liu, Xin Guo, Huifang Hu, Rui Sun, Tao Chen, Yan Liu and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Review
  6. Frontiers in pharmacology · 2026
    Review
  7. Review
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Chenxi ZhuDepartment of Rheumatology and Immunology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
Jiayi XuDepartment of Rheumatology and Immunology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
Siyu HeNational Clinical Research Center for Geriatrics, Department of General Practice, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
Qian NiuDepartment of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
Yi LiuDepartment of Rheumatology and Immunology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
Xin GuoDepartment of Rheumatology and Immunology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
Huifang HuDepartment of Rheumatology and Immunology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
Rui SunDepartment of Rheumatology and Immunology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
Tao ChenDepartment of Rheumatology and Immunology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
Yan LiuDepartment of Rheumatology and Immunology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
Zhiqiang XuNational Clinical Research Center for Geriatrics, Department of General Practice, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
Na JiangAdvanced Mass Spectrometry Center and Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610213, P. R. China.
Lipu YaoDepartment of Rheumatology and Immunology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
Lunzhi DaiNational Clinical Research Center for Geriatrics, Department of General Practice, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
Qinghua ZouDepartment of Rheumatology and Immunology, First Affiliated Hospital of Army Military Medical University, Chongqing, 400038, P. R. China.
Fanxin ZengDepartment of Big Data and Biomedical AI, College of Future Technology, Peking University, Beijing, 100871, P .R. China.
Liesu MengNational-Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, P. R. China.
Inger GjertssonDepartment of Rheumatology and Inflammation Research, Institute for Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden.
Rikard HolmdahlNational-Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, P. R. China.
Bin YangDepartment of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
Dan DuAdvanced Mass Spectrometry Center and Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610213, P. R. China.
Yi ZhaoDepartment of Rheumatology and Immunology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.ORCID https://orcid.org/0000-0002-8522-8906

Funding

China Postdoctoral Science Foundation 2024M762247Key Research and Development Projects of Shaanxi Province 2024GH-ZDXM-34National Key Research and Development Program of China 2019YFE0108200National Natural Science Foundation of China 82272400National Natural Science Foundation of China 82402111National Natural Science Foundation of China 82471830National Natural Science Foundation of China W2431021Post-doctor Research Fund of West China Hospital, Sichuan University 2024HXBH038Science Popularization Base Project of Chengdu Science and Technology Bureau 2022-GH03-00003-HZSichuan International Science and Technology Cooperation Project 2022YFH0023Sichuan International Science and Technology Cooperation Project 2024JDHJ0044Sichuan International Science and Technology Cooperation Project 2024YFHZ0231Special Fund for Central Guidance on Local Science and Technology Development from the Sichuan Provincial Department of Science and Technology 2024ZYD0285West China Hospital 1.3.5 Project for Disciplines of Excellence 21HXFH002West China Hospital Hospital-Enterprise Cooperation Clinical Research Innovation Project 21HXCX004
6 · The paper itself

Abstract

Rheumatoid arthritis (RA) is a systemic inflammatory joint disease characterized by heterogeneous clinical manifestations, which requires deeper exploration in identifying reliable biomarkers for early diagnosis, monitoring, and treatment assessment. The aim is to discover plasma metabolomic markers to predict RA onset, assess disease activity, and forecast treatment efficacy. The study includes 209 established RA patients who are disease-modifying antirheumatic drugs-free for six months prior to enrollment, with 197 of them followed for 3-6 months to assess treatment response. Additionally, 56 individuals at risk are recruited, with 34 completing a 5-7-year follow-up. Analysis reveals that metabolites related to methylation and redox imbalance, such as S-adenosylmethionine, sarcosine, nicotinamide adenine dinucleotide, glutathione, etc., are associated with RA development and severity, and contribute to its heterogeneity across age, sex, and anti-citrullinated protein autoantibody status. Ridge regression models are constructed using metabolite and clinical features for the response to methotrexate (MTX) plus leflunomide, achieving an average receiver operating characteristic (ROC) score of 0.83, and for the MTX plus hydroxychloroquine, achieving an average ROC score of 0.92. In conclusion, our findings reveal RA metabolomic alterations, aiding early diagnosis and treatment response.

Indexed as

Arthritis, RheumatoidBiomarkersMetabolomicsAdultAgedAntirheumatic AgentsFemaleHumansHydroxychloroquineLeflunomideLongitudinal StudiesMaleMethotrexateMiddle AgedSeverity of Illness IndexTreatment OutcomeAntirheumatic AgentsBiomarkersHydroxychloroquineLeflunomideMethotrexatelongitudinal profilingmachine learningmetabolomicsrheumatoid arthritistherapy response

Identifiers

PMID40801465
PMCPMC12520550

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.