BACKGROUND: While indirect comparison of infliximab (IFX) and vedolizumab (VDZ) in adults with Crohn's disease (CD) or ulcerative colitis (UC) shows that IFX has better effectiveness during induction, and comparable efficacy during maintenance treatment, comparative data specific to subcutaneous (SC) IFX (i.e., CT-P13 SC) versus VDZ are limited. AIM: Pooled analysis of randomised studies to compare efficacy and safety with IFX SC and VDZ in moderate-to-severe inflammatory bowel disease. METHODS: Parallel-group, randomised studies evaluating IFX SC and VDZ in patients with moderate-to-severe CD or UC were identified. Eligible studies reported ≥ 1 prespecified outcome of interest at Week 6 (reflecting treatment during the induction phase) and/or at 1 year (Weeks 50-54; reflecting treatment during the maintenance phase). Prespecified efficacy and safety outcomes considered in this pooled analysis included the proportions of patients achieving disease-specific clinical responses, clinical remission, or discontinuing due to lack of efficacy, and the proportions of patients experiencing adverse events (AEs), serious AEs, infections, serious infections, or discontinuing due to AEs. Data from multiple studies or study arms were extracted and pooled using a random-effect model; comparative analyses were performed separately for patients with CD and UC. RESULTS: We identified three eligible CD trials and four eligible UC trials that assigned over 1200 participants per disease cohort to either IFX SC or VDZ. In patients with CD, intravenous induction therapy with IFX demonstrated better efficacy (non-overlapping 95% confidence intervals [CIs]) compared with VDZ; during the maintenance phase, IFX SC showed numerically better efficacy (overlapping 95% CIs) than VDZ. A lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In patients with UC, efficacy profiles were similar with IFX SC and VDZ during the induction and maintenance phases, and a lower proportion of IFX SC-treated patients discontinued therapy due to lack of efficacy over 1 year. In both cohorts, safety profiles for IFX SC and VDZ were generally comparable during 1 year. CONCLUSION: IFX SC demonstrated better efficacy than VDZ in patients with CD, and similar efficacy to VDZ in patients with UC; 1-year safety was comparable with IFX SC and VDZ.
- MeSH
- Crohnova nemoc * farmakoterapie MeSH
- dospělí MeSH
- gastrointestinální látky škodlivé účinky MeSH
- humanizované monoklonální protilátky * MeSH
- indukce remise MeSH
- infliximab škodlivé účinky MeSH
- lidé MeSH
- randomizované kontrolované studie jako téma MeSH
- ulcerózní kolitida * farmakoterapie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- hospitalizace MeSH
- lidé MeSH
- mladý dospělý MeSH
- parenterální výživa MeSH
- průjem etiologie patologie MeSH
- ulcerózní kolitida * komplikace terapie MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Úvod a ciele: Nedávno bol schválený prvý subkutánny infliximab (IFX), CTP-13, v indikácii IBD. Pilotná štúdia preukázala noninferioritu subkutánneho infliximabu voči intravenóznej forme z hľadiska účinnosti, pričom neboli pozorované žiadne neočakávané nežiaduce účinky liečby. Cieľom štúdie bolo zhodnotiť účinnosť liečby, farmakokinetiku a bezpečnosť po prechode z intravenóznej na subkutánnu liečbu infliximabom. Metódy: Táto retrospektívna kohortová štúdia zah?ňala všetkých pacientov s Crohnovou chorobou (CD) a ulceróznou kolitídou (UC) sledovaných v IBD centre, ktorí prešli z intravenózneho na subkutánny IFX medzi septembrom 2022 a septembrom 2023. Klinická aktivita ochorenia podľa HBI a pMayo, sIBDQ, fekálny kalprotektín, perzistencia liečby, bezpečnosť a farmakokinetika boli hodnotené v 24. a 56. týždni po prechode na subkutánny infliximab. Výsledky: Kohorta pozostávala z 107 pacientov (63 CD a 44 UC). Indexy kvality života a klinickej aktivity ochorenia zostali nezmenené pri CD aj UC. Fekálny kalprotektín sa významne znížil pri CD, ale nie pri UC. Pacienti, ktorým bol IV IFX podávaný v štandardnom režime, ako aj tí na intenzifikovaných režimoch, vykazovali podobné výsledky pri štandardnom SC dávkovaní. Nevyskytli sa žiadne závažné nežiaduce udalosti. Prechodné injekčné reakcie sa vyskytli u 4,7 % pacientov. Medián najnižších hladín infliximabu sa významne zvýšil po prechode na subkutánnu formu. Záver: Prechod z intravenózneho infliximabu na subkutánny je bezpečnou a účinnou možnosťou liečby pacientov so zápalovým ochorením čriev vrátane tých s aktivitou ochorenia a/alebo na intenzifikovanom intravenóznom režime infliximabu.
Background and aims: Recently, the first subcutaneous infliximab (IFX), CTP-13, was approved in the indication of IBD. Pivotal study established noninferiority of subcutaneous infliximab to intravenous formulation in terms of efficacy, with no unexpected safety signals observed. The aims of the study were to evaluate persistency of treatment, pharmacokinetics and safety following a switch from intravenous to subcutaneous infliximab treatment. Methods: This retrospective, single-centre cohort study, recruited all Crohn’s disease (CD) and ulcerative colitis (UC) patients who transitioned from intravenous to subcutaneous IFX between September 2022 and September 2023. Clinical disease activity according to HBI and pMayo, sIBDQ, faecal calprotectin, drug persistence, safety and pharmacokinetics were evaluated at week 24 and 56 after the switch to subcutaneous infliximab. Results: A number of 107 patients was included (63 CD and 44 UC). Quality of life and clinical disease activity scores remained unchanged both in CD and UC. Faecal calprotectin decreased significantly in CD but not in UC. Patients that had been on standard compared to intensified IV infliximab dosing displayed similar outcomes on standard SC dosing. No serious adverse events occurred. Transient local injection reactions were experienced by 4.7% of patients. Median infliximab trough levels significantly increased after the switch to subcutaneous formulation. Conclusion: The switch from intravenous to subcutaneous infliximab is a safe and effective option for the treatment of inflammatory bowel diseases including those with active disease and/or on intensified intravenous infliximab regime.
- MeSH
- biologické přípravky aplikace a dávkování farmakologie terapeutické užití MeSH
- Crohnova nemoc * farmakoterapie MeSH
- infliximab * aplikace a dávkování farmakologie terapeutické užití MeSH
- intravenózní podání MeSH
- lidé MeSH
- retrospektivní studie MeSH
- subkutánní infuze MeSH
- ulcerózní kolitida * farmakoterapie MeSH
- Check Tag
- lidé MeSH
Based on the mimicry of microbial metabolites, functionalized indoles were demonstrated as the ligands and agonists of the pregnane X receptor (PXR). The lead indole, FKK6, displayed PXR-dependent protective effects in DSS-induced colitis in mice and in vitro cytokine-treated intestinal organoid cultures. Here, we report on the initial in vitro pharmacological profiling of FKK6. FKK6-PXR interactions were characterized by hydrogen-deuterium exchange mass spectrometry. Screening FKK6 against potential cellular off-targets (G protein-coupled receptors, steroid and nuclear receptors, ion channels, and xenobiotic membrane transporters) revealed high PXR selectivity. FKK6 has poor aqueous solubility but was highly soluble in simulated gastric and intestinal fluids. A large fraction of FKK6 was bound to plasma proteins and chemically stable in plasma. The partition coefficient of FKK6 was 2.70, and FKK6 moderately partitioned into red blood cells. In Caco2 cells, FKK6 displayed high permeability (A-B: 22.8 × 10-6 cm.s-1) and no active efflux. These data are indicative of essentially complete in vivo absorption of FKK6. The data from human liver microsomes indicated that FKK6 is rapidly metabolized by cytochromes P450 (t1/2 5 min), notably by CYP3A4. Two oxidized FKK6 derivatives, including DC73 (N6-oxide) and DC97 (C19-phenol), were detected, and these metabolites had 5-7 × lower potency as PXR agonists than FKK6. This implies that despite high intestinal absorption, FKK6 is rapidly eliminated by the liver, and its PXR effects are predicted to be predominantly in the intestines. In conclusion, the PXR ligand and agonist FKK6 has a suitable pharmacological profile supporting its potential preclinical development.
BACKGROUND AND AIMS: Ulcerative proctitis [UP] is an uncommon presentation in paediatric patients with ulcerative colitis. We aimed to characterize the clinical features and natural history of UP in children, and to identify predictors of poor outcomes. METHODS: This was a retrospective study involving 37 sites affiliated with the IBD Porto Group of ESPGHAN. Data were collected from patients aged <18 years diagnosed with UP between January 1, 2016 and December 31, 2020. RESULTS: We identified 196 patients with UP (median age at diagnosis 14.6 years [interquartile range, IQR 12.5-16.0]), with a median follow-up of 2.7 years [IQR 1.7-3.8]. The most common presenting symptoms were bloody stools [95%], abdominal pain [61%] and diarrhoea [47%]. At diagnosis, the median paediatric ulcerative colitis activity index [PUCAI] score was 25 [IQR 20-35], but most patients exhibited moderate-severe endoscopic inflammation. By the end of induction, 5-aminosalicylic acid administration orally, topically or both resulted in clinical remission rates of 48%, 48%, and 73%, respectively. The rates of treatment escalation to biologics at 1, 3, and 5 years were 10%, 22%, and 43%, respectively. In multivariate analysis, the PUCAI score at diagnosis was significantly associated with initiation of systemic steroids, or biologics, and subsequent acute severe colitis events and inflammatory bowel disease-associated admission, with a score ≥35 providing an increased risk for poor outcomes. By the end of follow-up, 3.1% of patients underwent colectomy. Patients with UP that experienced proximal disease progression during follow-up [48%] had significantly higher rates of a caecal patch at diagnosis and higher PUCAI score by the end of induction, compared to those without progression. CONCLUSION: Paediatric patients with UP exhibit high rates of treatment escalation and proximal disease extension.
- MeSH
- biologické přípravky * terapeutické užití MeSH
- dítě MeSH
- idiopatické střevní záněty * farmakoterapie MeSH
- lidé MeSH
- mladiství MeSH
- proktitida * diagnóza etiologie MeSH
- retrospektivní studie MeSH
- ulcerózní kolitida * komplikace diagnóza farmakoterapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- multicentrická studie MeSH
BACKGROUND: The societal burden of inflammatory bowel diseases (IBD) is not well documented, and further studies are needed to quantify the costs of the disease state. Thus, the aim was to estimate the societal burden and identify its predictors. METHODS: A cross-sectional questionnaire-based study complemented by objective data from patient medical records was performed for patients with Crohn's disease (CD) and ulcerative colitis (UC). RESULTS: We analyzed data from 161 patients (CD: 102, UC: 59). The overall work impairment reached 15.4%, 11.2% vs. 28.8% without/with self-reported symptoms (p = 0.006). Daily activity impairment was 19.3%, 14.1% vs. 35.6% (p < 0.001). The disability pension rate was 28%, 23% vs. 44% (p = 0.012). The total productivity loss due to absenteeism, presenteeism, and disability amounted to 7,673 €/patient/year, 6,018 vs. 12,354 €/patient/year (p = 0.000). Out-of-pocket costs amounted to 562 €/patient/year, 472 vs. 844 €/patient/year (p = 0.001). Self-reported symptoms were the strongest predictor of costs (p < 0.001). CONCLUSION: We found a high societal burden for IBD and a significant association between patient-reported disease symptoms and work disability, daily activity impairment, disability pensions, and out-of-pocket costs. Physician-reported disease activity is not a reliable predictor of costs except for out-of-pocket expenses.
In the past decade, single-cell transcriptomics has helped to uncover new cell types and states and led to the construction of a cellular compendium of health and disease. Despite this progress, some difficult-to-sequence cells remain absent from tissue atlases. Eosinophils-elusive granulocytes that are implicated in a plethora of human pathologies1-5-are among these uncharted cell types. The heterogeneity of eosinophils and the gene programs that underpin their pleiotropic functions remain poorly understood. Here we provide a comprehensive single-cell transcriptomic profiling of mouse eosinophils. We identify an active and a basal population of intestinal eosinophils, which differ in their transcriptome, surface proteome and spatial localization. By means of a genome-wide CRISPR inhibition screen and functional assays, we reveal a mechanism by which interleukin-33 (IL-33) and interferon-γ (IFNγ) induce the accumulation of active eosinophils in the inflamed colon. Active eosinophils are endowed with bactericidal and T cell regulatory activity, and express the co-stimulatory molecules CD80 and PD-L1. Notably, active eosinophils are enriched in the lamina propria of a small cohort of patients with inflammatory bowel disease, and are closely associated with CD4+ T cells. Our findings provide insights into the biology of eosinophils and highlight the crucial contribution of this cell type to intestinal homeostasis, immune regulation and host defence. Furthermore, we lay a framework for the characterization of eosinophils in human gastrointestinal diseases.
- MeSH
- analýza genové exprese jednotlivých buněk MeSH
- antigeny CD80 metabolismus MeSH
- eozinofily * klasifikace cytologie imunologie metabolismus MeSH
- idiopatické střevní záněty imunologie MeSH
- imunita * MeSH
- interferon gama MeSH
- interleukin 33 MeSH
- kolitida * imunologie patologie MeSH
- lidé MeSH
- myši MeSH
- proteom MeSH
- střeva * imunologie patologie MeSH
- T-lymfocyty MeSH
- transkriptom MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
This article offers insights into eating practices, conceptualising and making of 'good' food by people living with chronic disease. Based on ethnographic research focussing on people with Inflammatory Bowel Disease (Crohn's disease, ulcerative colitis and undefined IBD) in the Czech Republic, we explore what it would mean to conceptualise disability from the non-normative gut. We trace the practices of tinkering with foods and one's body, and ways of learning to sense (with) dysbiotic guts that people with IBD develop. Departing from the established notions of digestion and metabolism as universal biological processes, people with IBD create an embodied crip archive of knowledge through their eating practices, ways of making and sensing food and metabolic sampling. Most importantly, these practices offer, as we argue, new pathways into exploring crip embodiments as a place from which to acknowledge and do more-than-human collaboration, heath and ecologies.
- MeSH
- Crohnova nemoc * MeSH
- idiopatické střevní záněty * MeSH
- lidé MeSH
- potraviny MeSH
- ulcerózní kolitida * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Ulcerózní kolitida (UC) je spolu s Crohnovou chorobou (CN) a indeterminovanou kolitidou řazena mezi idiopatické střevní záněty (IBD – inflammatory bowel disease). Ani jedna ze zmíněných nemocí není v současné době žádnou terapií definitivně vyléčitelná a hlavním terapeutickým cílem je dosažení trvalé hluboké remise, která je definována jako absence subjektivních obtíží bez přítomnosti zánětlivé aktivity detekovatelné laboratorně, endoskopicky či na zobrazovacích metodách. Základem terapie IBD je komplexní pojetí péče o nemocné, zahrnující dominantně léčbu farmakologickou, chirurgickou, endoskopickou či nutriční a psychologickou. U většiny pacientů umožňuje podávaná terapie potlačit klinické projevy nemoci, zabránit vzniku komplikací, vést kvalitní osobní i pracovní život včetně snížení invalidity a dlouhodobé pracovní neschopnosti. Zavedením biologické a inovativní léčby (tzv. malými molekulami) se výrazně zvýšila kvalita života našich nemocných, snížila se potřeba chirurgických výkonů a minimalizovalo se riziko rozvoje nevratných strukturálních změn trávicího traktu.
Ulcerative colitis (UC), Crohn's disease (CN) and indeterminate colitis belong to a group of chronic conditions known as inflammatory bowel diseases (IBD). There is no medication that can cure ulcerative colitis, and the main therapeutic aim is to achieve deep remission, which is defined as the laboratory and endoscopic remission and the absence of subjective disorders. IBD treatment usually involves pharmacological, surgical, endoscopic, nutritional and psychological therapy. The administered therapy improves the clinical symptoms of the disease, prevents complications, and allows patients to lead a high-quality personal and working life, including a reduction of longterm incapacity for work. Biological and small molecules treatment significantly increases the quality of life of our patients, reduces the need for surgical intervention, and minimizes the risk of irreversible structural damage of the colon.
