Trial reportInflammatory bowel diseases2021
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.
Trial report in Inflammatory bowel diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02365649 (A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Upadacitinib), which is not on this map. Cited by 15 papers, 1 of them a synthesis 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.
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Upadacitinib (ABT-494) for the Induction of Symptomatic and Endoscopic Remission in Subjects With Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or Are Intolerant to Immunomodulators or Anti-TNF Therapy
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Safety and efficacy of different JAK inhibitors in the treatment of inflammatory bowel disease: a network meta-analysis.Frontiers in pharmacology · 2025Pooled it
- Mast cell-derived IL-13 as a driver of Crohn disease-associated intestinal fibrosis.Inflammatory bowel diseases · 2026Article
- Neuronal responses to cytokines limit intestinal hypermotility and systemic effects of colonic inflammation.iScience · 2026Article
- A Real-World Study of Upadacitinib in Anti-TNF Refractory Crohn's Disease: Effectiveness, Persistence, and Safety.Journal of inflammation research · 2026Article
- Upadacitinib induction therapy in Crohn' s disease: a retrospective real-world study in biologic-refractory patients.BMC gastroenterology · 2025Article
- Therapeutic potential of Janus kinase inhibitors for the management of fibrosis in inflammatory bowel disease.Journal of Crohn's & colitis · 2025Review
- The Cell-Specific Effects of JAK1 Inhibitors in Ulcerative Colitis.Journal of clinical medicine · 2025Review
- Real-World Effectiveness and Safety of Selective JAK Inhibitors in Ulcerative Colitis and Crohn's Disease: A Retrospective, Multicentre Study.Journal of clinical medicine · 2024Article
- Successful treatment of Crohn's disease-related peripheral spondyloarthritis with upadacitinib: two case reports and case-based review.Rheumatology international · 2024Review
- Advancements in Targeted Therapies for the Management of Crohn's Disease: A Comprehensive Review.Cureus · 2024Review
- A Narrative Review of Cytokine Networks: Pathophysiological and Therapeutic Implications for Inflammatory Bowel Disease Pathogenesis.Biomedicines · 2023Review
- Upadacitinib in Crohn's Disease: A Comprehensive Systematic Review of Efficacy and Safety.Cureus · 2023Review
- Identifying high-impact variants and genes in exomes of Ashkenazi Jewish inflammatory bowel disease patients.Nature communications · 2023Article
- Regulation of CEACAM Family Members by IBD-Associated Triggers in Intestinal Epithelial Cells, Their Correlation to Inflammation and Relevance to IBD Pathogenesis.Frontiers in immunology · 2021Article
- Upadacitinib Treatment Outcomes in Crohn's Disease: A Retrospective Analysis of Clinical Response and Perianal Fistula Resolution.Inflammatory intestinal diseasesArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundJanus kinase (JAK) inhibition shows promise for treatment of patients with moderate to severe Crohn's disease. We aimed to provide mechanistic insights into the JAK1-selective inhibitor upadacitinib through a transcriptomics substudy on biopsies from patients with Crohn's disease from CELEST.
methodsSeventy-four patients consented to this optional substudy. Ileal and colonic biopsies were collected during endoscopy at screening and week 12 or 16. RNA isolated from 226 samples was analyzed by RNAseq, with additional qPCR analysis. Additional biopsies from patients with Crohn's disease receiving anti-tumor necrosis factor (anti-TNF; n = 34) and healthy controls (n = 10) were used for qPCR. Single-cell RNAseq public profiles were used to evaluate treatment effects on specific cellular subsets, associations with endoscopic improvement, and indirect comparisons with the anti-TNF-treated cohort.
resultsIn involved areas of mucosa with endoscopic remission after upadacitinib treatment, 1156 and 76 protein-coding genes were significantly regulated (false discovery rate < 0.05) at week 12/16 in colonic and ileal biopsies, respectively (60 overlapped), compared with baseline. Upadacitinib did not significantly affect transcriptomes of noninvolved intestinal areas. CELEST patients (mostly anti-TNF-refractory) showed baseline differences in gene expression compared with a separate cohort of biologic-naïve patients. Notably, upadacitinib reversed overexpression of inflammatory fibroblast and interferon-γ effector signature markers.
conclusionsUpadacitinib modulates inflammatory pathways in mucosal lesions of patients with anti-TNF-refractory Crohn's disease, including inflammatory fibroblast and interferon-γ-expressing cytotoxic T cell compartments. This substudy is the first to describe the molecular response to JAK1 inhibition in inflammatory bowel disease and differential effects relative to anti-TNF treatment. (Clinical trial identifier: NCT02365649).
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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.