SynthesisJournal of Crohn's & colitis2018
Primary Non-Response to Tumor Necrosis Factor Antagonists is Associated with Inferior Response to Second-line Biologics in Patients with Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis.
Synthesis in Journal of Crohn's & colitis, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06520397 (Evaluation of the Efficacy and Safety of Dual-targeted Therapy With Upadacitinib and Ustekinumab Versus Intensified Ustekinumab Therapy in Crohn's Disease Patients With an Insufficient Response to Standard-dose Ustekinumab), which is not on this map. Cited by 143 papers, 6 of them syntheses that pooled 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.
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.
Evaluation of the Efficacy and Safety of Dual-targeted Therapy With Upadacitinib and Ustekinumab Versus Intensified Ustekinumab Therapy in Crohn's Disease Patients With an Insufficient Response to Standard-dose Ustekinumab: A Randomized Controlled Trial
Who cites it
143 citing papers in PubMed, 6 syntheses or guidelines pooled it, 209 citations in OpenAlex.
- Dual biologics or combination therapy with small molecules in pediatric inflammatory bowel disease: a systematic review and meta-analysis.World journal of pediatrics : WJP · 2026Pooled it
- EARLY ILEOCECAL RESECTION IN CROHN'S DISEASE: A SYSTEMATIC REVIEW.Arquivos de gastroenterologia · 2026Pooled it
- Efficacy and safety of Mirikizumab in the treatment of moderate to severe inflammatory bowel diseases: a systematic review and updated meta-analysis.Inflammopharmacology · 2025Pooled it
- Biological Therapy and Small Molecules for Adults With Crohn's Disease: Systematic Review and Network Meta-Analysis.Pharmacotherapy · 2025Pooled it
- AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis.Gastroenterology · 2020Guideline
- Use of TNF Inhibitors in Rheumatoid Arthritis and Implications for the Periodontal Status: For the Benefit of Both?Frontiers in immunology · 2020Pooled it
- Effect of Mirikizumab on Clinical and Endoscopic Outcomes Based on Prior Advanced Therapy Failure in Patients With Moderately to Severely Active Ulcerative Colitis.United European gastroenterology journal · 2026Trial
- Risankizumab efficacy and safety based on prior inadequate response or intolerance to advanced therapy: post hoc analysis of the INSPIRE and COMMAND phase 3 studies.Journal of Crohn's & colitis · 2025Trial
- A phase IB/IIA study of remestemcel-L, an allogeneic bone marrow-derived mesenchymal stem cell product, for the treatment of medically refractory ulcerative colitis: an interim analysis.Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland · 2022Trial
- Uninflamed colonic tissue harbors humoral activity linked to anti-TNF therapy non-response in ulcerative colitis.iScience · 2026Article
- Efficacy and Safety of Ozanimod in Ulcerative Colitis: A Real-World Pan-Hellenic Study.Medicina (Kaunas, Lithuania) · 2026Article
- Comparative efficacy of ustekinumab and vedolizumab in anti-TNF-naive and anti-TNF-exposed patients with Crohn's disease: a matched cohort study.Proceedings (Baylor University. Medical Center) · 2026Article
- 5-OH-TMT mitigates colitis through HTRA2 binding-mediated activation of the Dectin-1 signaling pathway.Acta pharmacologica Sinica · 2026Article
- Ustekinumab Persistence in Biologic-Experienced Crohn's Disease Patients: A Single-Center Retrospective Cohort Study.Medicina (Kaunas, Lithuania) · 2026Article
- Review
- Targeted and quantitatively modeled biologic delivery via dual-functional probiotic yeast in inflammatory bowel disease.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- Resistance Training Complements Anti-TNF Therapy in DSS-Induced Colitis by Improving Skeletal Muscle Inflammatory and Mitochondrial Gene Signatures.Current issues in molecular biology · 2026Article
- Review
- Hydrodynamic Delivery of IL-10 Gene for Local Immunomodulation in Human Crohn's Disease Tissue: A Proof-of-Concept Study.Pharmaceutics · 2026Article
- The duration of prior anti-tumor necrosis factor agents is associated with the effectiveness of vedolizumab in patients with ulcerative colitis: a real-world multicenter retrospective study.Intestinal research · 2026Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
aimsWe sought to analyze whether response to a second-line biologic varies depending on the reason for discontinuation of the primary anti-TNF agent (primary non-response [PNR], secondary loss of response [LOR] after initial response, or intolerance), through a systematic review and meta-analysis.
methodsThrough a systematic search through May 31, 2017, we identified eight randomized controlled trials [RCTs] of biologics in patients with IBD with prior exposure to anti-TNF agents, that stratified response to second-line therapy by reason for discontinuing primary anti-TNF therapy [PNR vs. LOR vs. intolerance]. We estimated relative risk [RR] (and 95% confidence interval [CI]) of achieving clinical remission in patients with PNR as compared with patients with LOR, and intolerance, through random effects meta-analysis.
resultsAs compared with patients who discontinued prior anti-TNF due to intolerance, patients with prior PNR were 24% less likely to achieve remission with second-line biologics (RR,0.76 [0.61-0.96]). As compared with patients who discontinued prior anti-TNF due to LOR, patients with prior PNR were 27% less likely to achieve remission with induction therapy with second-line biologics (RR,0.73 [0.56-0.97]), particularly to ustekinumab (RR,0.64 [0.52-0.80]). There was no difference in response to vedolizumab in patients with prior PNR or LOR to anti-TNF agents (RR,1.16 [0.85-1.58]).
conclusionPatients with PNR to anti-TNF agents are less likely to respond to second-line non-TNF biologics, as compared with patients who discontinued therapy due to secondary LOR or intolerance. This may be attributed to underlying pharmacokinetics and pharmacodynamics of anti-TNF agents in patients with PNR.
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What OpenQuestion holds
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.