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- MeSH
- adalimumab * farmakologie terapeutické užití MeSH
- biosimilární léčivé přípravky klasifikace terapeutické užití MeSH
- dospělí MeSH
- hidradenitis suppurativa farmakoterapie imunologie MeSH
- idiopatické střevní záněty * diagnóza farmakoterapie imunologie klasifikace MeSH
- inhibitory TNF klasifikace terapeutické užití MeSH
- lidé MeSH
- ulcerózní kolitida farmakoterapie imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) are endowed with the ability of establishing lifelong latency in human hosts and reactivating in immunocompromised subjects, including patients suffering from ulcerative colitis (UC). We, therefore, aimed to investigate virus-specific immunity in UC patients. A cohort of 24 UC patients (14 responders and 10 refractory to therapy) and 26 control subjects was prospectively enrolled to undergo virus-specific serology (by ELISA assay) and assessment of both CD4+ and CD8+ virus-specific T-cell response (by interferon-γ enzyme-linked immunospotanalysis). In parallel, mucosal viral load was determined by quantitative real-time PCR and the values were correlated with both clinical and endoscopic indexes of activity. For statistics, the t-test, Mann-Withney test, Fisher's exact test and Spearman rank correlation test were applied; p < 0.05 was considered significant. EBV-specific CD4+ and CD8+ T-cell responses were significantly lower in UC patients compared to controls (p < 0.0001 and p = 0.0006, respectively), whereas no difference was found for HCMV-specific T-cell response. When dividing the UC group according to response to therapy, both responders and refractory UC patients showed a deficient EBV-specific CD4+ T-cell response with respect to controls (p < 0.04 and p = 0.0003, respectively). Moreover, both EBV and HCMV mucosal loads were significantly higher in refractory UC than in responders and controls (p = 0.007 and 0.003; and p = 0.02 and 0.001, respectively), and correlated with activity indexes. Steroid therapy seemed the main risk factor for triggering EBV colitis. Finally, no cases of IgM positivity were found in the study population. An impaired EBV-specific immunity was clearly evident in UC patients, mostly in those refractory to therapy. The ELISPOT assay may serve as new tool for quantifying and monitoring virus-specific T-cell immunity in UC.
- MeSH
- CD4-pozitivní T-lymfocyty metabolismus MeSH
- CD8-pozitivní T-lymfocyty metabolismus MeSH
- cytomegalovirové infekce farmakoterapie imunologie MeSH
- Cytomegalovirus imunologie fyziologie MeSH
- DNA virů genetika MeSH
- infekce virem Epsteina-Barrové farmakoterapie imunologie MeSH
- lidé MeSH
- prospektivní studie MeSH
- steroidy škodlivé účinky terapeutické užití MeSH
- studie případů a kontrol MeSH
- ulcerózní kolitida farmakoterapie imunologie virologie MeSH
- virová nálož MeSH
- virus Epsteinův-Barrové imunologie fyziologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND AIMS: Ontamalimab, a fully-human monoclonal antibody targeting MAdCAM-1, induced remission in patients with moderate-to-severe ulcerative colitis [UC] in the TURANDOT study. We aimed to assess long-term safety, tolerability, and efficacy of ontamalimab in TURANDOT II. METHODS: TURANDOT II was a phase 2, multicentre, open-label [OL] study in patients with moderate-to-severe UC who completed TURANDOT on placebo or ontamalimab (NCT01771809). Patients were randomised to 75 mg or 225 mg ontamalimab every 4 weeks for 72 weeks [OL1]. The dosage could be increased to 225 mg from Week 8 at the investigator's discretion. All patients then received 75 mg every 4 weeks for 72 weeks [OL2], followed by 6-month safety follow-up. The primary objective was safety, measured by adverse events [AEs], serious AEs [SAEs], and AEs leading to withdrawal. Mucosal healing [MH; centrally read endoscopy] was assessed. RESULTS: Of 330 patients, 180 completed OL1; 94 escalated to 225 mg; 127 completed OL2. Overall, 36.1% experienced drug-related AEs. The most common SAE [10.0%] was worsening/ongoing UC; 5.5% of patients had serious infections, the most common being gastroenteritis [0.9%]. One death and four cancers [all unrelated to ontamalimab] occurred. No PML [progressive multifocal leukoencephalopathy]/lymphoproliferative disorders occurred. Geometric mean high-sensitivity C-reactive protein [hsCRP] and faecal calprotectin decreased across OL1 in both dose groups. The proportion of patients assigned to placebo in TURANDOT achieving MH increased from 8.8% [6/68] at baseline to 35.3% at Week 16 [24/68; non-responder imputation]. The corresponding increase in the ontamalimab group was from 23.3% [61/262] to 26.7% [70/262]. CONCLUSIONS: Ontamalimab was well tolerated up to 144 weeks in patients with moderate-to-severe UC, with good safety and efficacy.
- MeSH
- C-reaktivní protein analýza MeSH
- dospělí MeSH
- gastrointestinální endoskopie metody statistika a číselné údaje MeSH
- gastrointestinální látky aplikace a dávkování škodlivé účinky MeSH
- humanizované monoklonální protilátky * aplikace a dávkování škodlivé účinky MeSH
- imunologická odpověď na dávku MeSH
- leukocytární L1-antigenní komplex analýza MeSH
- lidé MeSH
- molekuly buněčné adheze antagonisté a inhibitory MeSH
- monitorování léčiv * metody statistika a číselné údaje MeSH
- mukoproteiny antagonisté a inhibitory MeSH
- ulcerózní kolitida * diagnóza farmakoterapie imunologie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
BACKGROUND AND AIMS: Vedolizumab was shown to be safe and effective for the treatment of Crohn's disease [CD] and ulcerative colitis [UC] in the GEMINI Long-Term Safety [LTS] study. The vedolizumab Extended Access Program [XAP] provides patients with continued treatment. This XAP pharmacokinetics [PK] sub-study investigated vedolizumab efficacy, safety, and PK. METHODS: Vedolizumab dosing frequency was reduced from every 4 weeks [Q4W] to every 8 weeks [Q8W] at XAP enrolment, and patients were followed for 56 weeks. Outcomes included: efficacy, loss of clinical benefit, and re-escalation to Q4W dosing; and vedolizumab PK, immunogenicity, and adverse events. RESULTS: Among 167 enrolled patients [CD = 88, UC = 79], 80 [91%] with CD and 73 [92%] with UC completed 56 weeks; 76 [86%] and 71 [90%] with CD and UC, respectively, remained on Q8W dosing for 56 weeks. Clinical remission, corticosteroid-free clinical remission, and C-reactive protein levels were stable among patients remaining on Q8W through Week 56. Four patients with CD and two with UC resumed Q4W dosing [three with CD regained clinical response]. Patients with CD who completed Week 56 on Q8W dosing had median trough vedolizumab concentrations of 43.6 µg/mL at enrolment and 10.4 µg/mL at Week 56; concentrations were 42.4 µg/mL and 13.3 µg/mL, respectively, in patients with UC. Treatment-related adverse events were infrequent; no new or serious adverse events related to vedolizumab were reported. CONCLUSIONS: In the XAP-PK sub-study, adherence to Q8W dosing was high, with no loss of efficacy; very few patients required re-escalation to Q4W. There were no new safety signals.
- MeSH
- Crohnova nemoc * diagnóza farmakoterapie imunologie MeSH
- dospělí MeSH
- gastrointestinální látky aplikace a dávkování škodlivé účinky farmakokinetika MeSH
- humanizované monoklonální protilátky * aplikace a dávkování škodlivé účinky farmakokinetika MeSH
- imunologická odpověď na dávku MeSH
- integriny antagonisté a inhibitory MeSH
- intravenózní infuze MeSH
- lidé MeSH
- monitorování léčiv metody MeSH
- ulcerózní kolitida * diagnóza farmakoterapie imunologie MeSH
- vysazování léků metody MeSH
- výsledky a postupy - zhodnocení (zdravotní péče) MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze IV MeSH
- klinické zkoušky MeSH
- multicentrická studie MeSH
BACKGROUND: Vaccine-preventable diseases and opportunistic infections in pediatric inflammatory bowel disease (IBD) are increasingly recognized issues. The aims of this study were to evaluate vaccinations, immunization status, and consequent therapeutic management in children with IBD and to analyze the differences among patients diagnosed before (Group 1) and after June 2012 (Group 2). METHODS: This was a multicenter, retrospective cohort investigation. Between July 2016 and July 2017, 430 children with IBD were enrolled in 13 centers. Diagnosis, therapeutic history, vaccinations, and immunization status screening at diagnosis and at immunosuppressant (IM)/biologic initiation and reasons for incomplete immunization were retrieved. RESULTS: Vaccination rates at diagnosis were unsatisfactory for measles, mumps, and rubella (89.3%), Haemophilus influenzae (81.9%), meningococcus C (23.5%), chickenpox (18.4%), pneumococcus (18.6%), papillomavirus (5.9%), and rotavirus (1.9%). Complete immunization was recorded in 38/430 (8.8%) children, but specific vaccines were recommended in 79/430 patients (18.6%), without differences between the 2 groups. At IM start, 22% of children were tested for Epstein-Barr virus (EBV) status, with 96.2% of EBV-naïve patients starting azathioprine, without differences between Groups 1 and 2. Screening for latent tuberculosis (TB) before start of biologics was performed in 175/190 (92.1%), with up to 9 different screening strategies and numerous inconsistencies. CONCLUSIONS: We demonstrated a poor immunization status at diagnosis in children with IBD, which was not followed by proper vaccination catch-up. EBV status before IM initiation and latent TB before biologics were not adequately assessed. Thus, the overall impact of the current guidelines seems unsatisfactory.
- MeSH
- Crohnova nemoc farmakoterapie imunologie MeSH
- dítě MeSH
- dodržování směrnic MeSH
- idiopatické střevní záněty farmakoterapie imunologie MeSH
- imunosupresiva škodlivé účinky MeSH
- infekce virem Epsteina-Barrové prevence a kontrola MeSH
- latentní tuberkulóza prevence a kontrola MeSH
- lidé MeSH
- Mycobacterium tuberculosis MeSH
- očkovací schéma MeSH
- oportunní infekce imunologie prevence a kontrola MeSH
- retrospektivní studie MeSH
- ulcerózní kolitida farmakoterapie imunologie MeSH
- vakcinace normy statistika a číselné údaje MeSH
- virus Epsteinův-Barrové MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Idiopatické střevní záněty (IBD) jsou skupinou onemocnění, jejichž příčina není zcela jasná a kde předpokládáme, že se na jejich vzniku podílí jak faktory genetické, tak i vnější vlivy. Léčba je tedy komplikovaná, jejím základem jsou aminosalicyláty, kortikoidy, imunosupresiva a v posledních letech také biologická léčba. Probiotika jsou specifické živé mikroorganismy, jež mohou příznivě ovlivňovat či zlepšit zdravotní stav jedince, pokud jsou přijímány v dostatečném množství. Jejich význam v léčbě idiopatických střevních zánětů není dominantní, mají však svůj prokázaný význam v prevenci pouchitidy a v udržovací léčbě ulcerózní kolitidy.
Crohn´s disease and ulcerative colitis are inflammatory bowel diseases, whose cause is not clear. We expected, that genetic and external factors participate in to their origin. The treatment of Crohn´s disease and ulcerative colitis is complicated and aminosalicylates, corticosteroids, immunosuppressants, and recently also biological therapy are the basis of the treatment of inflammatory bowel diseases (IBD). Probiotics are living microorganisms of the human origin, that can influence human health, if they are used in sufficient quantities. Their position in IBD treatment is not dominant, but they are important in the long-term treatment of ulcerative colitis and in prevention of pouchitis.
- MeSH
- Crohnova nemoc imunologie mikrobiologie terapie MeSH
- idiopatické střevní záněty * farmakoterapie imunologie mikrobiologie MeSH
- lidé MeSH
- probiotika aplikace a dávkování terapeutické užití MeSH
- ulcerózní kolitida imunologie mikrobiologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND AND AIMS: Intestinal inflammation in inflammatory bowel diseases [IBD] is thought to be T cell mediated and therefore dependent on the interaction between the T cell receptor [TCR] and human leukocyte antigen [HLA] proteins expressed on antigen presenting cells. The collection of all TCRs in one individual, known as the TCR repertoire, is characterised by enormous diversity and inter-individual variability. It was shown that healthy monozygotic [MZ] twins are more similar in their TCR repertoire than unrelated individuals. Therefore MZ twins, concordant or discordant for IBD, may be useful to identify disease-related and non-genetic factors in the TCR repertoire which could potentially be used as disease biomarkers. METHODS: Employing unique molecular barcoding that can distinguish between polymerase chain reaction [PCR] artefacts and true sequence variation, we performed deep TCRα and TCRβ repertoire profiling of the peripheral blood of 28 MZ twin pairs from Denmark and Germany, 24 of whom were discordant and four concordant for IBD. RESULTS: We observed disease- and smoking-associated traits such as sharing, diversity and abundance of specific clonotypes in the TCR repertoire of IBD patients, and particularly in patients with active disease, compared with their healthy twins. CONCLUSIONS: Our findings identified TCR repertoire features specific for smokers and IBD patients, particularly when signs of disease activity were present. These findings are a first step towards the application of TCR repertoire analyses as a valuable tool to characterise inflammatory bowel diseases and to identify potential biomarkers and true disease causes.
- MeSH
- C-reaktivní protein analýza MeSH
- Crohnova nemoc * diagnóza imunologie patofyziologie MeSH
- dospělí MeSH
- dvojčata monozygotní MeSH
- feces MeSH
- geny TcR alfa * MeSH
- geny TcR beta * MeSH
- kouření imunologie MeSH
- leukocytární L1-antigenní komplex analýza MeSH
- lidé MeSH
- posouzení stavu pacienta MeSH
- receptory antigenů T-buněk alfa-beta krev MeSH
- sekvenční analýza DNA MeSH
- ulcerózní kolitida * diagnóza imunologie patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- studie na dvojčatech MeSH
- Geografické názvy
- Dánsko MeSH
- Německo MeSH
Idiopatické střevní záněty jsou skupinou onemocnění, jejichž příčina není zcela jasná a kde předpokládáme, že se na jejich vzniku podílí jak faktory genetické, tak i vnější vlivy. Léčba je tedy komplikovaná, jejím základem jsou aminosalicyláty, kortikoidy, imunosupresiva a v posledních letech také biologická léčba. Probiotika jsou specifické živé mikroorganismy, jež mohou příznivě ovlivňovat či zlepšit zdravotní stav jedince, pokud jsou přijímány v dostatečném množství. Jejich význam v léčbě idiopatických střevních zánětů není dominantní, mají však svůj prokázaný význam v prevenci pouchitidy a v udržovací léčbě ulcerózní kolitidy.
Crohn´s disease and ulcerative colitis are inflammatory bowel diseases, whose cause is not clear. We expected, that genetic and external factors participate in to their origin. The treatment of Crohn´s disease and ulcerative colitis is complicated and aminosalicylates, corticosteroids, immunosuppressants, and recently also biological therapy are the basis of the treatment of inflammatory bowel diseases (IBD). Probiotics are living microorganisms of the human origin, that can influence human health, if they are used in sufficient quantities. Their position in IBD treatment is not dominant, but they are important in the long-term treatment of ulcerative colitis and in prevention of pouchitis.
- MeSH
- Crohnova nemoc imunologie mikrobiologie terapie MeSH
- idiopatické střevní záněty * farmakoterapie imunologie mikrobiologie MeSH
- lidé MeSH
- probiotika aplikace a dávkování terapeutické užití MeSH
- ulcerózní kolitida imunologie mikrobiologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
