SynthesisGut2019
Cell-centred meta-analysis reveals baseline predictors of anti-TNFα non-response in biopsy and blood of patients with IBD.
Synthesis in Gut, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 4 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
124 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Multi-Omics Biomarkers for Predicting Efficacy of Biologic and Small-Molecule Therapies in Adults With Inflammatory Bowel Disease: A Systematic Review.United European gastroenterology journal · 2025Pooled it
- Lymphocyte subsets for predicting inflammatory bowel disease progression and treatment response: a systematic review.Frontiers in immunology · 2024Pooled it
- Meta-analysis of gene expression disease signatures in colonic biopsy tissue from patients with ulcerative colitis.Scientific reports · 2021Pooled it
- Pooled it
- Baseline TREM-1 Whole Blood Gene Expression Does Not Predict Response to Adalimumab Treatment in Patients with Ulcerative Colitis or Crohn's Disease in the SERENE Studies.Journal of Crohn's & colitis · 2024Trial
- Randomized Controlled Trial Substudy of Cell-specific Mechanisms of Janus Kinase 1 Inhibition With Upadacitinib in the Crohn's Disease Intestinal Mucosa: Analysis From the CELEST Study.Inflammatory bowel diseases · 2021Trial
- Uninflamed colonic tissue harbors humoral activity linked to anti-TNF therapy non-response in ulcerative colitis.iScience · 2026Article
- TREM1 signaling amplifies neutrophil-mediated inflammation in inflammatory bowel disease.Nature communications · 2026Article
- Serum or Plasma Oncostatin M for Predicting Primary Non-Response to Tumor Necrosis Factor-α Antagonist Therapy in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.Clinics and practice · 2026Review
- Epigenetic biomarkers in inflammatory bowel diseases-computational challenges and opportunities.Journal of Crohn's & colitis · 2026Review
- Advancing IBD Management: A Literature Review on the Role of Non-Invasive Blood-Based Biomarkers in Predicting and Assessing Pharmacodynamic Response to Treatment.Clinical and translational science · 2026Review
- Combining Cytokine-Related Biomarkers to Better Define Tumor Necrosis Factor-α Antagonist Response in Inflammatory Bowel Disease: An Observational Cohort Study.Clinical and translational gastroenterology · 2026Observational
- Depletion of IgG-producing plasma cells in the colon by treatment of proteasome inhibitor ameliorates chronic DSS-induced colitis in mice.Scientific reports · 2026Article
- Inflammatory and Immune Pathways Driving Tumor Necrosis Factor Inhibitor Resistance in Ulcerative Colitis.Journal of inflammation research · 2026Review
- Spatial multi-omics-guided drug development in inflammatory bowel disease: from mucosal immune niches to precision therapy.Frontiers in immunology · 2026Review
- Multi-omics analysis identifies fibroblast IGFBP5 as a key target of anti-TNFα therapy in ulcerative colitis.Frontiers in immunology · 2026Article
- A single-cell atlas of ulcerative colitis reveals neutrophil-stromal circuits linked to biologic therapy resistance.Frontiers in immunology · 2026Article
- TREM1 facilitates nonresponse to anti-TNF-α monoclonal antibodies in colitis via boosting ITCH/TAK1/caspase-8 axis-mediated macrophage pyroptosis.Journal of translational medicine · 2025Article
- Mucosal kinase activity and inflammatory profiles in inflammatory bowel disease, and in relation to tofacitinib response.Journal of Crohn's & colitis · 2025Article
- DNAzyme targeting RIP3 suppresses NLRP3-mediated necroinflammation for the treatment of inflammatory diseases.Acta pharmaceutica Sinica. B · 2025Article
64 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
objectiveAlthough anti-tumour necrosis factor alpha (anti-TNFα) therapies represent a major breakthrough in IBD therapy, their cost-benefit ratio is hampered by an overall 30% non-response rate, adverse side effects and high costs. Thus, finding predictive biomarkers of non-response prior to commencing anti-TNFα therapy is of high value.
designWe analysed publicly available whole-genome expression profiles of colon biopsies obtained from multiple cohorts of patients with IBD using a combined computational deconvolution-meta-analysis paradigm which allows to estimate immune cell contribution to the measured expression and capture differential regulatory programmes otherwise masked due to variation in cellular composition. Insights from this in silico approach were experimentally validated in biopsies and blood samples of three independent test cohorts.
resultsWe found the proportion of plasma cells as a robust pretreatment biomarker of non-response to therapy, which we validated in two independent cohorts of immune-stained colon biopsies, where a plasma cellular score from inflamed biopsies was predictive of non-response with an area under the curve (AUC) of 82%. Meta-analysis of the cell proportion-adjusted gene expression data suggested that an increase in inflammatory macrophages in anti-TNFα non-responding individuals is associated with the upregulation of the triggering receptor expressed on myeloid cells 1 (TREM-1) and chemokine receptor type 2 (CCR2)-chemokine ligand 7 (CCL7) -axes. Blood gene expression analysis of an independent cohort, identified TREM-1 downregulation in non-responders at baseline, which was predictive of response with an AUC of 94%.
conclusionsOur study proposes two clinically feasible assays, one in biopsy and one in blood, for predicting non-response to anti-TNFα therapy prior to initiation of treatment. Moreover, it suggests that mechanism-driven novel drugs for non-responders should be developed.
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Registered trials
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.