ArticleInflammatory bowel diseases2022
Antitumor Necrosis Factor-like Ligand 1A Therapy Targets Tissue Inflammation and Fibrosis Pathways and Reduces Gut Pathobionts in Ulcerative Colitis.
Article in Inflammatory bowel diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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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.
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Who cites it
35 citing papers in PubMed, 49 citations in OpenAlex.
- A phase 1 study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of PF-07261271 in healthy participants.British journal of clinical pharmacology · 2026Trial
- Article
- TL1A inhibitors in inflammatory bowel disease: A systematic review of phase 2 clinical trials.Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association · 2026Article
- Targeting IBD treatment: smart drug delivery systems for oral administration.Materials today. Bio · 2026Review
- Therapeutic Potential of Tulisokibart and Anti-TL1A Therapy in Inflammatory Disorders: Current Insights and Future Directions.Clinical reviews in allergy & immunology · 2026Review
- Precision Medicine in Inflammatory Bowel Disease: The Emerging Role of Metabolic Dysfunction.Journal of personalized medicine · 2026Review
- Article
- Treat-to-Target in Ulcerative Colitis: How Soon Is Now?Journal of clinical medicine · 2026Article
- Switching Between Anti-TNFs and Other Biologic Drugs in Paediatric Inflammatory Bowel Disease: A Narrative Review and Practical Clinical Guide.Journal of inflammation research · 2026Review
- Selective Nanoparticulate Systems for Drug Delivery in Inflammatory Bowel Disease.Pharmaceutics · 2025Review
- Beyond inflammation: what drives the self-perpetuating cycle of fibrosis in IBD?Annals of medicine · 2025Review
- The association of proton pump inhibitors and inflammatory bowel disease from the perspective of gut microbiota perturbation.NPJ biofilms and microbiomes · 2025Review
- The Role of Post-Translational Modifications in Necroptosis.Biomolecules · 2025Review
- Review
- TL1A Inhibition in Inflammatory Bowel Disease: A Pipeline Review.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Deciphering the immunocellular regulatory network in inflammatory bowel disease: from susceptibility genes to cellular effectors and toward precision therapies.Frontiers in immunology · 2025Review
- Targeting the TNF and TNFR superfamilies in autoimmune disease and cancer.Nature reviews. Drug discovery · 2024Review
- RIPK3 and caspase-8 interpret cytokine signals to regulate ILC3 survival in the gut.Mucosal immunology · 2024Article
- Targeting TNF/TNFR superfamilies in immune-mediated inflammatory diseases.The Journal of experimental medicine · 2024Review
- Preventing fibrosis in IBD: update on immune pathways and clinical strategies.Expert review of clinical immunology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe first-in-class treatment PF-06480605 targets the tumor necrosis factor-like ligand 1A (TL1A) molecule in humans. Results from the phase 2a TUSCANY trial highlighted the safety and efficacy of PF-06480605 in ulcerative colitis. Preclinical and in vitro models have identified a role for TL1A in both innate and adaptive immune responses, but the mechanisms underlying the efficacy of anti-TL1A treatment in inflammatory bowel disease (IBD) are not known.
methodsHere, we provide analysis of tissue transcriptomic, peripheral blood proteomic, and fecal metagenomic data from the recently completed phase 2a TUSCANY trial and demonstrate endoscopic improvement post-treatment with PF-06480605 in participants with ulcerative colitis.
resultsOur results revealed robust TL1A target engagement in colonic tissue and a distinct colonic transcriptional response reflecting a reduction in inflammatory T helper 17 cell, macrophage, and fibrosis pathways in patients with endoscopic improvement. Proteomic analysis of peripheral blood revealed a corresponding decrease in inflammatory T-cell cytokines. Finally, microbiome analysis showed significant changes in IBD-associated pathobionts, Streptococcus salivarius, S. parasanguinis, and Haemophilus parainfluenzae post-therapy.
conclusionsThe ability of PF-06480605 to engage and inhibit colonic TL1A, targeting inflammatory T cell and fibrosis pathways, provides the first-in-human mechanistic data to guide anti-TL1A therapy for the treatment of IBD.
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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.