OBJECTIVES: The phase 2 MANTA and MANTA-RAy studies aimed to determine if the oral Janus kinase 1 preferential inhibitor filgotinib affects semen parameters and sex hormones in men with inflammatory diseases. METHODS: MANTA (NCT03201445) and MANTA-RAy (NCT03926195) included men (21-65 years) with active inflammatory bowel disease (IBD) and rheumatic diseases (rheumatoid arthritis, spondyloarthritis or psoriatic arthritis), respectively. Eligible participants had semen parameters in the normal range per the WHO definition. In each study, participants were randomised 1:1 to receive once-daily, double-blind filgotinib 200 mg or placebo for 13 weeks for pooled analysis of the primary endpoint (proportion of participants with a ≥50% decrease from baseline in sperm concentration at week 13). Participants who met the primary endpoint were monitored over an additional 52 weeks for 'reversibility'. Secondary endpoints included change from baseline to week 13 in: sperm concentration, total motility, normal morphology, total count and ejaculate volume. Sex hormones (luteinising hormone, follicle stimulating hormone, inhibin B and total testosterone) and reversibility were exploratory endpoints. RESULTS: Across both studies, 631 patients were screened, and 248 were randomised to filgotinib 200 mg or placebo. Baseline demographics and characteristics were similar within indications between treatment groups. Numerically similar proportions of filgotinib-treated versus placebo-treated patients met the primary endpoint (8/120 (6.7%) vs 10/120 (8.3%)), Δ-1.7% (95% CI -9.3% to 5.8%)). There were no clinically relevant changes from baseline to week 13 in semen parameters or sex hormones, or patterns of reversibility between treatment groups. Filgotinib was well tolerated, with no new safety events. CONCLUSIONS: Results suggest that once daily filgotinib 200 mg for 13 weeks has no measurable impact on semen parameters or sex hormones in men with active IBD or inflammatory rheumatic diseases.
- MeSH
- dvojitá slepá metoda MeSH
- idiopatické střevní záněty * farmakoterapie chemicky indukované MeSH
- inhibitory Janus kinas * terapeutické užití MeSH
- lidé MeSH
- pohlavní steroidní hormony terapeutické užití MeSH
- revmatoidní artritida * farmakoterapie MeSH
- sperma MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze II MeSH
- randomizované kontrolované studie MeSH
BACKGROUND AND AIMS: SARS-CoV-2 is a worldwide serious health problem and vaccination seems to have a crucial role in managing the COVID-19 pandemic. The aim of this prospective observational study was to monitor the trend of antibodies against SARS-CoV-2 after vaccination with BNT162b2 (COMIRNATY) in patients with inflammatory bowel disease treated by immunosuppressive and/or biological therapy, demonstrate whether any type of this therapy is associated with poorer production of antibodies against COVID-19 and evaluate the safety of vaccination against COVID-19 in these patients. METHODS: Eighty-seven eligible patients from one tertiary gastroenterological center with inflammatory bowel disease (60 with CD, 27 with UC) treated by immunosuppressive and/or biological therapy from the antiTNFα group were indicated to vaccination against SARS-CoV-2. Effectiveness of vaccination was evaluated by the values of antibodies before and 4 weeks after 2nd dose of vaccine. Additional goal was to evaluate adverse events of vaccination. RESULTS: Before the 2nd dose of vaccine, geometric mean of SARS-CoV-2 IgG antibodies were 40.7 U/ml in the biological therapy group, 34.8 U/ml in the azathioprine group and 44.8 U/ml in the combination therapy group of patients. The geometric means were 676.5.7 U/ml in the biological therapy group, 614.4 U/ml in the azathioprine group and 500.1 U/ml in the combination therapy group of patients four weeks after 2nd dose. Statistically significant differences between these groups were not proved. Several non-severe local and general adverse events were present in our patients with a majority of these events on the day of vaccine administration and the day after, no anaphylactic reactions were present. CONCLUSIONS: Our measurements proved the efficacy and safety of vaccination against SARS-CoV-2 in patients with inflammatory bowel disease treated by immunosuppressive and/or biological therapy. Statistically significant differences between our groups of patients were not proved.
- MeSH
- azathioprin MeSH
- COVID-19 * prevence a kontrola MeSH
- idiopatické střevní záněty * chemicky indukované farmakoterapie MeSH
- lidé MeSH
- pandemie MeSH
- protilátky virové MeSH
- SARS-CoV-2 MeSH
- vakcína BNT162 MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 škodlivé účinky MeSH
- virové vakcíny * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
BACKGROUND AND AIMS: There are limited comparative data for infliximab and vedolizumab in inflammatory bowel disease patients. METHODS: We conducted a systematic review and meta-analysis to compare the efficacy and safety of infliximab and vedolizumab in adult patients with moderate-to-severe Crohn's disease or ulcerative colitis. RESULTS: We identified six eligible Crohn's disease and seven eligible ulcerative colitis trials that randomised over 1900 participants per disease cohort to infliximab or vedolizumab. In the Crohn's disease and ulcerative colitis cohorts, infliximab yielded better efficacy than vedolizumab for all analysed outcomes (CDAI-70, CDAI-100 responses, and clinical remission for Crohn's disease and clinical response and clinical remission for ulcerative colitis) during the induction phase, with non-overlapping 95% confidence intervals. In the maintenance phase, similar proportions of infliximab- or vedolizumab-treated patients achieved clinical response, clinical remission, or mucosal healing in both Crohn's disease and ulcerative colitis. For the safety outcomes, rates of adverse events, serious adverse events, and discontinuations due to adverse events were similar in infliximab- and vedolizumab-treated patients in both diseases. The infection rate was higher in infliximab for Crohn's disease and higher in vedolizumab when treating patients with ulcerative colitis. There was no difference between the treatments in the proportions of patients who reported serious infections in both indications. CONCLUSIONS: Indirect comparison of infliximab and vedolizumab trials in adult patients with moderate-to severe Crohn's disease or ulcerative colitis demonstrated that infliximab has better efficacy in the induction phase and comparable efficacy during the maintenance phase and overall safety profile compared to vedolizumab.
- MeSH
- Crohnova nemoc * chemicky indukované farmakoterapie MeSH
- dospělí MeSH
- gastrointestinální látky škodlivé účinky MeSH
- humanizované monoklonální protilátky MeSH
- idiopatické střevní záněty * chemicky indukované farmakoterapie MeSH
- infliximab škodlivé účinky MeSH
- lidé MeSH
- ulcerózní kolitida * chemicky indukované farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
BACKGROUND: Gastrointestinal injury caused by dextran sodium sulphate (DSS) is a reliable porcine experimental model of inflammatory bowel disease (IBD). The purpose of this study was to evaluate the effect of probiotic Lactobacillus casei DN 114001 (LC) on DSS-induced experimental IBD. RESULTS: Eighteen female pigs (Sus scrofa f. domestica, weight 33-36 kg, age 4-5 months) were divided into 3 groups (6 animals per group): controls with no treatment, DSS, and DSS + LC. LC was administered to overnight fasting animals in a dietary bolus in the morning on days 1-7 (4.5 × 1010 live bacteria/day). DSS was applied simultaneously on days 3-7 (0.25 g/kg/day). On day 8, the pigs were sacrificed. Histopathological score and length of crypts/glands (stomach, jejunum, ileum, transverse colon), length and width of villi (jejunum, ileum), and mitotic and apoptotic indices (jejunum, ileum, transverse colon) were assessed. DSS increased the length of glands in the stomach, length of crypts and villi in the jejunum and ileum, and the histopathological score of gastrointestinal damage, length of crypts and mitotic activity in the transverse colon. Other changes did not achieve any statistical significance. Administration of LC reduced the length of villi in the jejunum and ileum to control levels and decreased the length of crypts in the jejunum. CONCLUSIONS: Treatment with a probiotic strain of LC significantly accelerated regeneration of the small intestine in a DSS-induced experimental porcine model of IBD.
- Klíčová slova
- secukinumab,
- MeSH
- adalimumab terapeutické užití MeSH
- ankylózující spondylitida farmakoterapie MeSH
- idiopatické střevní záněty * chemicky indukované MeSH
- interleukin-17 MeSH
- kongresy jako téma MeSH
- lidé MeSH
- monoklonální protilátky * škodlivé účinky terapeutické užití MeSH
- psoriatická artritida farmakoterapie MeSH
- psoriáza farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- zprávy MeSH
OBJECTIVE: It is an open question whether multifunctional galectin-3 can be a serum marker in inflammatory bowel disease. METHODS: Western blots and commercial ELISA detected and quantitated the lectin immunocytochemistry using double labeling localized it in tissue sections. RESULTS: Serum concentrations were significantly increased in specimen of patients with active and remission-stage ulcerative colitis and Crohn's disease, associated with emerging positivity of CD14(+) cells. CONCLUSION: Enhanced concentration of galectin-3 in serum reflects presence of disease and points to its involvement in the pathogenesis.
- MeSH
- antigeny CD14 analýza metabolismus MeSH
- biologické markery MeSH
- Crohnova nemoc krev MeSH
- elektroforéza v polyakrylamidovém gelu MeSH
- Escherichia coli metabolismus MeSH
- fluorescein-5-isothiokyanát MeSH
- fluorescenční barviva MeSH
- galektin 3 krev MeSH
- idiopatické střevní záněty diagnóza chemicky indukované krev MeSH
- imunohistochemie MeSH
- kolitida chemicky indukované MeSH
- kolon metabolismus MeSH
- lektiny metabolismus MeSH
- lidé MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- síran dextranu MeSH
- ulcerózní kolitida krev MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
Paracetamol, pravděpodobně nejrozšířenější analgetikum, vzbuzuje stále výzkumný zájem. Mechanismus jeho léčebného účinku se do jisté míry blíží mechanismu účinku nesteroidních antirevmatik ze skupiny selektivních inhibitorů cyklooxygenázy 2. Není vyloučen podíl dlouhodobého podávání paracetamolu na rozvoji hypertenze a je možná i jeho úloha při aktivaci chronických zánětlivých střevních onemocnění.
Paracetamol, most probably the most frequently used analgetic, still inspires research interest. The mechanism of its treatment action resembles to a certain extent the mechanism of action of the non-steroid antirheumatics from the group of the cyclooxygenase 2 inhibitors. The contribution of the long-term administration of paracetamol on the development of hypertension can not be excluded and its role in the activation of the chronic inflammatory bowel diseases is possible.
- MeSH
- antirevmatika MeSH
- hypertenze chemicky indukované MeSH
- idiopatické střevní záněty chemicky indukované MeSH
- lékové interakce MeSH
- lidé MeSH
- paracetamol aplikace a dávkování farmakologie škodlivé účinky MeSH
- vyšetření krevní srážlivosti normy MeSH
- warfarin aplikace a dávkování škodlivé účinky MeSH
- Check Tag
- lidé MeSH
Mechanismus protizánětlivého účinku nesteroidních antirevmatik (NSA) spočívá v inhibici enzymatického komplexu cyklooxygenázy (COX), který katalyzuje tvorbu eikosanoidů (prostaglandinů a leukotrienů) z kyseliny arachidonové.
- MeSH
- adenomové polypy farmakoterapie prevence a kontrola MeSH
- antiflogistika nesteroidní škodlivé účinky MeSH
- chemoprofylaxe MeSH
- idiopatické střevní záněty farmakoterapie chemicky indukované MeSH
- inhibitory cyklooxygenasy 2 aplikace a dávkování farmakologie MeSH
- lidé MeSH
- střevní nádory prevence a kontrola MeSH
- Check Tag
- lidé MeSH