A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn's disease (PROFILE): a multicentre, open-label randomised controlled trial

˜The œLancet. Gastroenterology & hepatology, Год журнала: 2024, Номер 9(5), С. 415 - 427

Опубликована: Фев. 22, 2024

BackgroundManagement strategies and clinical outcomes vary substantially in patients newly diagnosed with Crohn's disease. We evaluated the use of a putative prognostic biomarker to guide therapy by assessing randomised either top-down (ie, early combined immunosuppression infliximab immunomodulator) or accelerated step-up (conventional) treatment strategies.MethodsPROFILE (PRedicting Outcomes For disease using moLecular biomarker) was multicentre, open-label, biomarker-stratified, controlled trial that enrolled adults active (Harvey-Bradshaw Index ≥7, elevated C-reactive protein faecal calprotectin both, endoscopic evidence inflammation). Potential participants had blood drawn be tested for derived from T-cell transcriptional signatures (PredictSURE-IBD assay). Following testing, were randomly assigned, via secure online platform, stratified subgroup (IBDhi IBDlo), inflammation (mild, moderate, severe), extent (colonic other). Blinding status maintained throughout trial. The primary endpoint sustained steroid-free surgery-free remission week 48. Remission defined composite symptoms inflammatory markers at all visits. Flare required (HBI ≥5) plus raised (CRP >upper limit normal ≥200 μg/g, both), while converse—ie, quiescent <5) resolved (both CRP ≤ upper <200 μg/g) both. Analyses done full analysis (intention-to-treat) population. has completed is registered (ISRCTN11808228).FindingsBetween Dec 29, 2017, Jan 5, 2022, 386 (mean age 33·6 years [SD 13·2]; 179 [46%] female, 207 [54%] male) randomised: 193 group group. Median time diagnosis enrolment 12 days (range 0–191). Primary outcome data available 379 (189 group; 190 group). There no biomarker–treatment interaction effect (absolute difference 1 percentage points, 95% CI –15 15; p=0·944). Sustained significantly more frequent than (149 [79%] 189 vs 29 [15%] patients, absolute 64 57 72; p<0·0001). fewer adverse events (including flares) serious (adverse events: 168 315; 15 42), complications requiring abdominal surgery (one ten) infections (three eight).InterpretationTop-down combination immunomodulator achieved better year treatment. did not show utility. Top-down should considered standard care disease.FundingWellcome PredictImmune Ltd.

Язык: Английский

---

Noninvasive, microbiome-based diagnosis of inflammatory bowel disease

Nature Medicine, Год журнала: 2024, Номер unknown

Опубликована: Окт. 4, 2024

Язык: Английский

---

Early Initiation of Biologics and Disease Outcomes in Adults and Children With Inflammatory Bowel Diseases: Results From the Epidemiology Group of the Nationwide Israeli Inflammatory Bowel Disease Research Nucleus Cohort

Gastroenterology, Год журнала: 2024, Номер 166(5), С. 815 - 825.e22

Опубликована: Фев. 6, 2024

Язык: Английский

---

Review article: Prevention of inflammatory bowel disease—The path forward

Alimentary Pharmacology & Therapeutics, Год журнала: 2024, Номер 60(9), С. 1166 - 1175

Опубликована: Окт. 15, 2024

Summary Background The possibility of preventing inflammatory bowel disease (IBD) is becoming more plausible due to advances in understanding preclinical and successful prevention trials other immune‐mediated diseases, such as type 1 diabetes rheumatoid arthritis. However, before that becomes reality, several efforts need occur parallel a coordinated way. Aim To propose some critical steps necessary for advancing the field IBD prediction prevention. Methods We reviewed current literature identify toward preventive strategy IBD. Results first step should determine most robust predictive biomarkers validate them across independent cohorts, creating multidimensional tool. second gain better preferences first‐degree relatives people at risk IBD, informing implementation screening strategies. Third, these contribute development high‐risk clinics establish networks trials. Conclusions Advancing will require multifaceted approach, integrating biomarker discovery, patient preferences, establishing infrastructure collaborative network support practical

Язык: Английский

---

From ASCA breakthrough in Crohn's disease and Candida albicans research to thirty years of investigations about their meaning in human health

Autoimmunity Reviews, Год журнала: 2023, Номер 23(2), С. 103486 - 103486

Опубликована: Ноя. 30, 2023

Anti-Saccharomyces cerevisiae antibodies (ASCA) are human that can be detected using an enzyme-linked immunosorbent assay involving a mannose polymer (mannan) extracted from the cell wall of yeast S. cerevisiae. The ASCA test was developed in 1993 with aim differentiating serological response two forms inflammatory bowel disease (IBD), Crohn's and ulcerative colitis. test, which is based on detection anti-oligomannosidic antibodies, has been extensively performed worldwide there have hundreds publications ASCA. earlier studies concerned initial diagnostic indications investigations then extended to many diseases, generally association intestinal microorganisms interaction micro-mycobiome immune system. more information accumulates, mystery meaning deepens. Many fundamental questions remain unanswered. These concern heterogeneity ASCA, mechanisms their generation persistence, existence self-antigens, relationship between inflammation autoimmunity. This review aims discuss gray areas concerning origin analysis literature. Structured around glycobiology mannosylated antigens Candida albicans, this will address these try clarify some lines thought. importance relating pathophysiological significance goes far beyond IBD, even though diseases preferred models for understanding.

Язык: Английский

---

Increased risk of obstructive lung disease in inflammatory bowel disease: A population‐based cohort study

United European Gastroenterology Journal, Год журнала: 2024, Номер 12(4), С. 477 - 486

Опубликована: Янв. 6, 2024

Abstract Background and Aims Inflammatory bowel disease (IBD) is associated with manifestations in organs other than the gastrointestinal tract. In this study, we aimed to estimate odds of obstructive lung (OLD) before IBD onset risk OLD after onset. Methods a nationwide population‐based Danish cohort study from 1999 2018, individuals were identified using registries. Between 2003 2013, 24,238 matched 1:10 non‐IBD individuals. Logistic regression was used prevalence ratio for Time‐to‐event analysis performed explore sensitivity analysis, time‐to‐event repeated composite outcome separate outcomes, chronic pulmonary (COPD), asthma, bronchiectasis. Results Individuals 60% more likely have (adjusted ratio: 1.60, 95% confidence interval [CI]: 1.53–1.67). Furthermore, their 40% higher diagnosis hazard [aHR]: 1.43, CI: 1.37–1.49). The increased (aHR: 1.63, 1.53–1.73). Similar results found COPD asthma separately, whereas bronchiectasis 2‐fold 2.44, 1.91–3.11). Conclusion before‐ following an increased. We encourage physicians be vigilant symptoms persons OLD.

Язык: Английский

---

The Earlier You Find, the Better You Treat: Red Flags for Early Diagnosis of Inflammatory Bowel Disease

Diagnostics, Год журнала: 2023, Номер 13(20), С. 3183 - 3183

Опубликована: Окт. 12, 2023

Delayed diagnosis is a challenge in the management of inflammatory bowel disease (IBD). Several studies show significant association between diagnostic delay and progression to complications surgery, especially Crohn’s (CD). What risk factors are associated with IBD remains unclear. In order reduce delay, Red Flags Index has been developed validated. The combination score non-invasive biomarkers such as fecal calprotectin seems be highly accurate screening patients underlying referred for further workup eventual early effective treatment strategies. Our literature review aims obtain comprehensive overview impacts on potential IBD, how tools may reducing future perspectives this field.

Язык: Английский

---

Immunological profile of lactylation-related genes in Crohn’s disease: a comprehensive analysis based on bulk and single-cell RNA sequencing data

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Март 23, 2024

Abstract Background Crohn's disease (CD) is a characterized by intestinal immune dysfunction, often accompanied metabolic abnormalities. Disturbances in lactate metabolism have been found the intestine of patients with CD, but studies on role and related Lactylation pathogenesis CD are still unknown. Methods We identified core genes associated downloading merging three CD-related datasets (GSE16879, GSE75214, GSE112366) from GEO database, analyzed functions hub correlation between their expression levels infiltration through comprehensive analysis. explored different cells using single-cell data further differences inflammatory non-inflammatory sites. Results six Lactylation-related that highly CD. Further analysis revealed these were correlated level cell infiltration. To clarify effect cells, we sequencing sites there significant types significantly higher Conclusions These results suggest closely changes patients.

Язык: Английский

---

The Time to Inflammatory Bowel Disease Diagnosis for Patients Presenting with Abdominal Symptoms in Primary Care and its Association with Emergency Hospital Admissions and Surgery: A Retrospective Cohort Study

Inflammatory Bowel Diseases, Год журнала: 2024, Номер 31(1), С. 140 - 150

Опубликована: Апрель 2, 2024

Patients with inflammatory bowel disease (IBD) presenting to primary care may experience diagnostic delays. We aimed evaluate this and assess whether time diagnosis is associated clinical outcomes.

Язык: Английский

---

Establishing key performance indicators for inflammatory bowel disease in the UK

Frontline Gastroenterology, Год журнала: 2023, Номер 14(5), С. 407 - 414

Опубликована: Май 25, 2023

Background and aims Healthcare quality improvement (QI) is the systematic process to continuously improve of care outcomes for patients. The landmark Inflammatory Bowel Disease (IBD) UK National Audits provided a means measure variation in care, highlighting need define standards excellence IBD care. Through consensus approach, we aimed establish key performance indicators (KPIs), providing reliable benchmarks delivery UK. Methods KPIs that critical aspects patient journey within an service were identified though stakeholder meetings. A two-stage Delphi was then conducted. first involved multidisciplinary team clinicians patients refine definitions methodology. second stage assessed feasibility utility proposed QI by surveying gastroenterology services across Results First, four refined included time from primary referral diagnosis secondary treatment recommendation following diagnosis, appropriate use steroids advanced therapies prescreening assessment. Second, reported >85% agreement on local adoption >75% benchmarking KPIs. Conclusions structured propose quantifiable reduce individual

Язык: Английский

---