BACKGROUND AND AIMS: Intestinal strictures are a common and serious adverse event of inflammatory bowel disease (IBD). Endoscopic balloon dilation (EBD) is the first step in treatment to avoid surgery. The aim of this study was to assess the prevalence, risk factors, and clinical sequelae of difficult EBD. METHODS: This retrospective, multicenter study included 861 patients with IBD treated with EBD due to strictures. Risk factors for difficult EBD, defined as ≥3 per year, were evaluated. RESULTS: During a median (IQR) of 23.00 (14.00-42.00) months of follow-up, there were 392 (45.5%) easier EBDs performed, while difficult EBDs were performed in 489 (54.5%) cases. Long-term efficacy of EBD, defined as >12 months without surgery, was achieved in 392 (100%) easier EBDs versus 457 (97.4%) difficult EBDs (Cramer's V = .11; P = .004). However, 149 (17.3%) patients underwent surgery for unsuccessful EBD. The most important risk factors for difficult EBD, classified as modifiable, were smoking and treatment with adalimumab (especially if trough levels were normal) and ustekinumab. Vedolizumab and immunosuppressive therapy were identified as protective factors. Multivariable logistic regression analysis indicated good fit of the model to the data, pointing to a protective role for total parental nutrition and worsening of smoking (both, P < .001). CONCLUSIONS: Reduction of difficult EBDs should be considered primarily in the context of their modifiable risk factors. Prospective studies with simultaneous evaluation of transmural healing are needed to truly assess whether vedolizumab treatment, immunosuppressive therapy, and total parenteral nutrition reduce the risk of EBD.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: A subcutaneous formulation of infliximab (IFX-SC) approved to treat patients with inflammatory bowel disease may offer improved efficacy versus intravenous infliximab. METHODS: Patients with refractory Crohn's disease (CD, n = 32) previously treated unsuccessfully with at least 2 biologics were treated with IFX-SC and followed from baseline at Week 0 (W0) to Week 30 (W30). The study's primary endpoint was the treatment's persistence at W30, while secondary goals included the analysis of serum infliximab trough levels (TL IFX), dynamics of anti-IFX antibodies (ATIs), and clinical, serum and fecal markers of CD activity during IFX-SC treatment. RESULTS: Midterm treatment persistence with the continuation of treatment after W30 was 53%. TL IFX median values showed rapid, significant upward dynamics and exceeded 15.5 μg/mL at W30, whereas median ATI levels significantly declined. Among ATI-negative patients at W0 (n = 15), only one showed IFX immunogenicity with newly developed ATIs at W30. Among ATI-positive patients at W0, ATI seroconversion from ATI-positive to ATI-negative status was observed in 10 of 17 patients (58.8%). Patients who had continued IFX-SC treatment at W30 showed significant decreases in C-reactive protein (P = .0341), fecal calprotectin (P = .0002), and Harvey-Bradshaw index (P = .0029) since W0. CONCLUSIONS: Patients with refractory CD previously treated with at least 2 biologics exhibited clinically relevant improvement with IFX-SC, which showed less immunogenic potential than IFX-IV and highly stable TL IFX.
- Klíčová slova
- Crohn’s disease, Inflammatory bowel disease, antibodies to infliximab, immunogenicity, infliximab, infliximab trough levels, subcutaneous, treatment persistence,
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Patients with inflammatory bowel disease (IBD) on immune-modifying treatment could be at an increased risk for severe coronavirus disease 2019 (COVID-19); thus, data on the efficacy and safety of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines are essential. We conducted a prospective study of IBD patients vaccinated with BNT162b2, CX-024414, and ChAdOx1 nCoV-19 vaccines. The aim was to evaluate the rate and magnitude of seroconversion, assess the effect of different immune-modifying treatment modalities on the magnitude of anti-SARS-CoV-2 IgG antibody levels, and analyze the impact of anti-SARS-CoV-2 vaccination on the inflammatory biomarkers of IBD. METHODS: The study included 602 IBD patients and 168 immunocompetent health care workers serving as controls. Serum anti-SARS-CoV-2 IgG antibodies were measured by chemiluminescent microparticle immunoassay before the vaccination and 8 weeks after the vaccination. RESULTS: Of IBD patients, 82.2% were receiving biological treatment: most of them were treated with antitumor necrosis factor (TNF)-α inhibitors (48.5%), and just under half of them were treated with concomitant thiopurines or methotrexate, followed by vedolizumab (18.6%) and ustekinumab (15.1%). Only 8.1% of patients were on 5-aminosalicylates, and a minority (2.2%) were treatment-free. The postvaccine seropositivity rate among IBD patients and controls was 97.8% vs 100%. Median anti-SARS-CoV-2 IgG levels were lower among IBD recipients of ChAdOx1 nCoV-19 compared with 2 other vaccines (P < .0001) and control ChAdOx1 nCoV-19 recipients (P = .01). No correlation was found between serum trough levels and anti-SARS-CoV-2 IgG concentrations for any of the biological drugs used. The TNF-α inhibitors with concomitant immunosuppressive treatment but no other treatment modalities were associated with a lower postvaccination antibody response (P < .0001). When evaluating the laboratory activity of IBD by C-reactive protein and fecal calprotectin levels, no significant differences were found before the vaccination and 8 weeks after its completion. CONCLUSIONS: Our findings warrant particular attention to the anti-SARS-CoV-2 vaccination of IBD patients treated with TNF-α inhibitors with concomitant immunomodulators and show the priority of mRNA vaccines in this specific group of patients.
- Klíčová slova
- BNT162b2, COVID-19, CX-024414, ChAdOx1 nCoV-19, Inflammatory bowel disease, SARS-CoV-2, immunity, vaccination,
- MeSH
- C-reaktivní protein metabolismus MeSH
- ChAdOx1 nCoV-19 MeSH
- COVID-19 * prevence a kontrola MeSH
- idiopatické střevní záněty * farmakoterapie MeSH
- imunoglobulin G MeSH
- leukocytární L1-antigenní komplex MeSH
- lidé MeSH
- methotrexát MeSH
- prospektivní studie MeSH
- protilátky virové MeSH
- SARS-CoV-2 MeSH
- TNF-alfa metabolismus MeSH
- tvorba protilátek MeSH
- ustekinumab MeSH
- vakcína BNT162 MeSH
- vakcinace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- C-reaktivní protein MeSH
- ChAdOx1 nCoV-19 MeSH
- imunoglobulin G MeSH
- leukocytární L1-antigenní komplex MeSH
- methotrexát MeSH
- protilátky virové MeSH
- TNF-alfa MeSH
- ustekinumab MeSH
- vakcína BNT162 MeSH
The development of new endoscopic methods is advancing rapidly. Current standard methods such as endoscopic balloon dilatation have only limited long-term effects. Surgery is more effective, but it also carries a higher risk of complications. Endoscopic stricturotomy and stricturoplasty are new methods expanding the range of possibilities of endoscopic treatment. These methods are advanced, technically demanding, and require adequate expertise and training. It is, therefore, necessary to have a tool for training and teaching these new methods. The live large animal model is a valuable tool in the development and testing of new, difficult, and dexterity intensive therapeutic methods thanks to its natural properties including bowel movements and tissue reactions such as swelling or bleeding. Animal model simulating secondary stricture in the site of the entero-colonic anastomosis has been created allowing not only to practice but also to develop new minimally invasive endoscopic techniques for the treatment of strictures in Crohn's disease (CD). High cost and stringent legislation represent the main limitations of more widespread use of large animal models in endoscopy.
- Klíčová slova
- Animal model, Inflammatory bowel disease, Stricture,
- MeSH
- Crohnova nemoc * komplikace chirurgie MeSH
- dilatace metody MeSH
- gastrointestinální endoskopie metody MeSH
- lidé MeSH
- prasata MeSH
- retrospektivní studie MeSH
- stenóza etiologie chirurgie MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND AND AIMS: Knowledge on the immunogenicity of anti-SARS-CoV-2 vaccines in inflammatory bowel disease [IBD] patients is limited. Therefore, SARS-CoV-2-specific T-cell responses and antibodies were analysed in 60 IBD vaccine recipients and 30 controls. METHODS: SARS-CoV-2 IgG antibodies against the viral spike protein were measured at baseline and at 8 and 26 weeks after the second vaccine dose. SARS-CoV-2 IgG antibodies against the nucleocapsid antigens were measured at week 26. A SARS-CoV-2 interferon-gamma released assay [IGRA] was performed in all vaccinees at week 26. RESULTS: At weeks 0 and 8, no differences were found in anti-spike antibodies between cohorts. At week 26, the decrease in antibody levels was more significant in the IBD cohort compared to the healthy cohort, and anti-nucleocapsid antibodies were not detected in either group. At week 26, 16 of 90 [18%] vaccinated individuals had a negative IGRA test result, seven of 90 [8%] were borderline and 67 [74%] had a positive IGRA result; 22 of the 23 individuals with negative or borderline IGRA results belonged to the IBD cohort. However, the overall functional ability of T-lymphocytes to produce interferon-gamma after the unspecific mitogen stimulation was lower in IBD patients. In vaccinated individuals with low or borderline IGRA, treatment with tumour necrosis factor-alpha inhibitors was the most frequent. In individuals with a significant drop in anti-spike antibody levels, plasmatic interferon-gamma concentrations after the specific SARS-CoV-2 stimulation were also insufficient. CONCLUSIONS: Simple humoral and cellular post-vaccination monitoring is advisable in IBD patients so that repeated vaccine doses may be scheduled.
- Klíčová slova
- COVID-19, inflammatory bowel disease, vaccination,
- MeSH
- COVID-19 * prevence a kontrola MeSH
- humorální imunita MeSH
- idiopatické střevní záněty * farmakoterapie MeSH
- imunoglobulin G MeSH
- interferon gama MeSH
- lidé MeSH
- protilátky virové MeSH
- SARS-CoV-2 MeSH
- vakcinace MeSH
- vakcíny proti COVID-19 MeSH
- virové vakcíny * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- imunoglobulin G MeSH
- interferon gama MeSH
- protilátky virové MeSH
- vakcíny proti COVID-19 MeSH
- virové vakcíny * MeSH
The majority of patients with Crohn's disease and a proportion of patients with ulcerative colitis will ultimately require surgical treatment despite advances in diagnosis, therapy, and endoscopic interventions. The surgical procedures that are most commonly done include bowel resection with anastomosis, strictureplasty, faecal diversion, and ileal pouch. These surgical treatment modalities result in substantial alterations in bowel anatomy. In patients with inflammatory bowel disease, endoscopy plays a key role in the assessment of disease activity, disease recurrence, treatment response, dysplasia surveillance, and delivery of endoscopic therapy. Endoscopic evaluation and management of surgically altered bowel can be challenging. This consensus guideline delineates anatomical landmarks and endoscopic assessment of these landmarks in diseased and surgically altered bowel.
- MeSH
- anastomóza chirurgická metody MeSH
- anatomická značka diagnostické zobrazování MeSH
- chirurgie trávicího traktu škodlivé účinky MeSH
- Crohnova nemoc diagnóza chirurgie MeSH
- dospělí MeSH
- endoskopie metody MeSH
- idiopatické střevní záněty chirurgie MeSH
- konsensus MeSH
- lidé středního věku MeSH
- lidé MeSH
- pouch škodlivé účinky MeSH
- proktokolektomie rekonstrukční metody MeSH
- recidiva MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- stenóza chirurgie MeSH
- střeva anatomie a histologie patologie chirurgie MeSH
- stupeň závažnosti nemoci MeSH
- ulcerózní kolitida diagnóza chirurgie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND: The increasing complexity of advanced endoscopic techniques places a high demand on the endoscopist's expertise. Thus, live porcine models have been more frequently used for training. We briefly describe a hands-on postgraduate endoscopic course regarding a novel method of treatment of anastomotic strictures in a porcine model. METHODS: The porcine model of Crohn's disease anastomotic stricture with two artificial side-to-side ileo-colonic anastomoses was used. Participants performed endoscopic stricturotomy under supervision at one of two equipped endoscopic stations. Available animals were endoscopically re-examined 3 months after the course. RESULTS: Twelve anastomoses were prepared for the course. Eleven circumferential stricturotomies together with horizontal cut and clip placement were conducted. All anastomoses were passable for the scope after the procedure, and no case of perforation or bleeding occurred. All anastomoses available for re-examination remained passable for the endoscope after 3 months. CONCLUSION: We successfully organised the first endoscopic hands-on course for the training of endoscopic stricturotomy on a large animal model.
- Klíčová slova
- Animal model, Crohn’s disease, Inflammatory bowel disease, Interventional endoscopy, Stricturotomy, Training,
- MeSH
- Crohnova nemoc * komplikace chirurgie MeSH
- dilatace MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- prasata MeSH
- stenóza etiologie chirurgie MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND AND AIMS: Currently, treatment options in postsurgical recurrence of stricturing Crohn's disease (CD) are limited. However, development of new invasive endoscopic techniques in clinical practice has safety constraints. The aim of this study was to create a large animal model of anastomotic stricture with CD properties to enable development of new techniques and training. METHODS: A side-to-side ileocolonic anastomosis was created in a modified Roux-en-Y manner with bowel continuity preserved. Two weeks after surgery, we began endoscopic submucosal injections of phenol/trinitrobenzenesulfonic acid solution. This solution was injected every 2 weeks in each quadrant of the anastomosis until development of a stricture. The anastomosis site was assessed endoscopically 2 weeks after the last application (baseline) and then every 2 months until month 6. Endoscopically nonpassable strictures were treated with balloon dilation, endoscopic stricturotomy, and stent placement to confirm the feasibility of such interventions. RESULTS: Nineteen minipigs were included with no postoperative adverse events. After a mean of 4.4 ± .7 injection sessions with 10.5 ± 3.0 mL of the solution, anastomotic strictures were created in 16 pigs (84.2%). Mean diameter of the strictures at baseline was 11.6 ± 2.2 mm. The strictures were inflamed, and the endoscope could not pass. Follow-up was successfully completed in 15 animals (79.0%) with the mean deviation from the initial diameter in every measurement of -.02 ± 2.26 mm (P = .963) and a mean final diameter of 11.7 ± 3.4 mm. The histopathologic evaluation revealed the presence of submucosal fibrosis, chronic inflammation, and microgranulomas. All strictures were amenable to endoscopic therapeutic interventions. CONCLUSIONS: We developed a novel, reproducible porcine model of anastomotic stricture with histologically verified changes mimicking CD and stable diameter for more than 6 months. It is suitable for further endoscopic interventions.
- MeSH
- Crohnova nemoc * chirurgie MeSH
- dilatace MeSH
- endoskopie MeSH
- lidé MeSH
- miniaturní prasata MeSH
- prasata MeSH
- retrospektivní studie MeSH
- stenóza etiologie MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND AIMS: Patients' perspectives after switching from originator to biosimilar adalimumab have yet to be assessed. We evaluated the efficacy of switching from the originator adalimumab to a biosimilar compound [SB5] in patients with inflammatory bowel disease [IBD]. METHODS: Data on IBD patients who were switched from the originator to biosimilar adalimumab [SB5] at IBD Center ISCARE were analysed. Disease activity was assessed using standard clinical indices (Harvey-Bradshaw index [HBI] for Crohn's disease [CD] and partial Mayo score for ulcerative colitis [UC]), and laboratory parameters (C-reactive protein [CRP] and faecal calprotectin [FC]). Trough levels and anti-drug antibodies were measured. Patients were evaluated 10 weeks [W10] after the switch, and results were compared with the control group of patients on originator compound. RESULTS: A total of 93 patients switched to biosimilar adalimumab were included [CD 86%] and were matched to 93 controls for age, gender, diagnosis, and disease activity. There was no difference in the disease activity in either SWITCH or ORIGINATOR cohorts between Weeks 0 and 10. Similarly, no difference was found between cohorts at both prespecified time points. Moreover, no significant differences in CRP or FC concentrations were seen between W0 and W10 either in the SWITCH, or in the ORIGINATOR cohort [p >0.05]. Adalimumab serum trough levels remained stable after the switch. No new safety signals were detected. CONCLUSIONS: Our study confirmed that switching IBD patients from the originator adalimumab to a biosimilar compound [SB5] does not affect treatment efficacy.
- Klíčová slova
- Adalimumab, biosimilar, inflammatory bowel disease,
- MeSH
- adalimumab krev imunologie terapeutické užití MeSH
- biosimilární léčivé přípravky krev terapeutické užití MeSH
- C-reaktivní protein metabolismus MeSH
- centra terciární péče MeSH
- Crohnova nemoc krev farmakoterapie MeSH
- dospělí MeSH
- feces chemie MeSH
- gastrointestinální látky krev imunologie terapeutické užití MeSH
- leukocytární L1-antigenní komplex analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- náhrada léků MeSH
- protilátky krev MeSH
- retrospektivní studie MeSH
- stupeň závažnosti nemoci MeSH
- ulcerózní kolitida krev farmakoterapie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adalimumab MeSH
- biosimilární léčivé přípravky MeSH
- C-reaktivní protein MeSH
- gastrointestinální látky MeSH
- leukocytární L1-antigenní komplex MeSH
- protilátky MeSH
