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Background and Aims Corticosteroid-free remission is a primary treatment goal in IBD which may be achieved with greater use of anti-TNF therapy. We defined temporal trends of corticosteroid use, anti-TNF use, hospitalization and surgery in a prevalent IBD cohort within the province of Alberta, Canada. Methods Health administrative data were used to identify medication dispensing, hospitalizations and surgery in individuals with IBD from 2010 to 2015. Temporal trends were calculated using log-binomial regression for medications and log-linear models for hospitalizations and surgery rates. Analyses were stratified based on geographic location. Results Of 28890 individuals with IBD, 50.3% had Crohn’s disease. One in six individuals (15.45%) were dispensed a corticosteroid. Corticosteroid use decreased in both metropolitan areas (AAPC −20.08%, 95% CI: −21.78 to −18.04) and non-metropolitan areas (AAPC −18.14%, 95% CI: −20.78 to −18.04) with a similar pattern for corticosteroid dependence. Corticosteroid dependence was more prevalent in UC vs. CD (P < 0.05), and in the pediatric IBD cohort (13.45) compared to the adult (8.89) and elderly (7.54) cohorts (per 100 prevalent population, P < 0.001). The proportion of individuals dispensed an anti-TNF increased over the study period (AAPC 12.58%, 95% CI: 11.56 to 13.61). Significantly more non-metropolitan versus metropolitan residing individuals were hospitalized for any reason, for an IBD-related, or IBD-specific indication (all P < 0.001) though the proportion requiring IBD surgery was similar between groups. Conclusions An increase in anti-TNF use corresponded to a decline in corticosteroid use and dependence in those with IBD. Inequities in IBD care still exist based on location and age.

Background Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Patients with inflammatory bowel disease are susceptible to Clostridium difficile infection (CDI). Here, we evaluate CDI in the tofacitinib UC clinical program. Methods Events from 4 randomized, placebo-controlled studies (phase [P] 2 or P3 induction [NCT00787202; NCT01465763; NCT01458951], P3 maintenance [NCT01458574]) and an open-label, long-term extension (OLE) study (NCT01470612), were analyzed as 3 cohorts: Induction (P2/P3 induction), Maintenance (P3 maintenance), and Overall (patients receiving tofacitinib 5 or 10 mg twice daily [BID] in P2, P3, and OLE studies; including final data from the OLE study, as of August 24, 2020). Proportions and incidence rates (unique patients with events per 100 patient-years of exposure) of CDI were evaluated. Results The overall cohort comprised 1157 patients who received ≥1 dose of tofacitinib 5 or 10 mg BID, with a total of 2814.4 patient-years of tofacitinib exposure and up to 7.8 years of treatment. A total of 82.6% of patients received predominantly tofacitinib 10 mg BID. In the induction, maintenance, and overall cohorts, 3 (2 tofacitinib treated, 1 placebo treated), 3 (all placebo treated), and 9 patients had CDI, respectively; the overall cohort incidence rate was 0.31 (95% confidence interval, 0.14-0.59). CDI were all mild–moderate in severity and resolved with treatment in 8 patients. Six of 9 patients continued tofacitinib treatment without interruption. Two patients had events reported as serious due to hospitalization. Two patients were receiving corticosteroids when the CDI occurred. Conclusion CDIs among patients with UC receiving tofacitinib were infrequent, cases were mild–moderate in severity, and most resolved with treatment.

Zusammenfassung Hintergrund Zur Diagnosestellung, Erkennung von Erkrankungskomplikationen sowie zur Verlaufskontrolle bei Patienten mit Morbus Crohn und Colitis ulcerosa wird zunehmend der Darmultraschall eingesetzt. Eine systematische Befunderhebung und Dokumentation sind wichtig, um die Qualität der Befunderstellung und die Kommunikation zwischen den Fachgruppen zu verbessern. Das vorliegende Positionspapier beschreibt die Voraussetzungen für eine optimale Befunderhebung des Darmultraschalls bei Patienten mit chronisch-entzündlichen Darmerkrankungen (CED). Methoden Eine Experten-Konsensusgruppe bestehend aus Gastroenterologen, Radiologen, Pathologen, Kinder- und Jugend-Gastroenterologen und Chirurgen führte eine systematische Literaturrecherche durch. In einem Delphi-Verfahren wurde unter Mitgliedern des Kompetenznetzes Darmerkrankungen und der Deutschen Röntgengesellschaft (DRG) über relevante Kriterien bei der Befunderhebung von Darmultraschallbefunden abgestimmt. Die daraus resultierenden Statements wurden in einer Experten-Konsensusgruppe verabschiedet. Ergebnis Praxisorientierte Empfehlungen für eine optimale Befunderhebung mit einer standardisierten Terminologie wurden entwickelt. Der Fokus der Erhebung lag auf der Beschreibung der Entzündungsaktivität sowie der Komplikationen bei CED. Minimale Anforderungen für eine standardisierte Befunderhebung wurden definiert. Zusammenfassung Das vorliegende Manuskript bietet praktische Empfehlungen zur Optimierung und Vereinheitlichung der Befunderhebung bei Darmultraschall-Untersuchungen bei CED.

Supplementary Table 1 from Systematic High-Content Proteomic Analysis Reveals Substantial Immunologic Changes in Colorectal Cancer

Newer Biologic and Small-Molecule Therapies for IBD There is still no cure for inflammatory bowel disease. This review covers newer treatments that reflect our understanding of the complex pathogen...

Background While no adverse developmental outcomes were observed in preclinical animal studies, limited data exist regarding effects of ustekinumab on human pregnancies. Previously, no data have been reported for women treated with ustekinumab in inflammatory bowel disease (IBD) clinical trials and corresponding pregnancy outcomes. Here, we present pregnancy outcomes from IBD clinical trials, incorporating 5 years of treatment in Crohn’s disease (CD) and 2 in ulcerative colitis (UC). Methods All patients in the clinical trials agreed to use adequate birth control and were discontinued from treatment upon pregnancy confirmation. Nonetheless, 39 pregnancies occurred with maternal ustekinumab exposure from 4 CD and 1 UC study. Maternal and neonatal outcomes and data are presented with summary statistics, where available. Results Of 1289 women who received ≥1 dose of ustekinumab, 39 maternal pregnancies with outcomes were reported (pregnancy cohort). Median maternal age was 28.0 years and median duration of ustekinumab treatment before pregnancy was 63.7 weeks with the last dose of ustekinumab administered prior to or during the first trimester (terminal half-life of ~3 weeks). Outcomes for the 39 pregnancies were: 26 live births (all normal newborns), 8 spontaneous abortions, and 5 elective abortions. No congenital anomalies were reported among normal newborns and no safety signals emerged with neonatal outcomes. Conclusions Based on this series of 39 pregnancies with outcomes from IBD clinical trials, mothers treated with ustekinumab (limited to up to the first trimester) did not demonstrate a risk of negative outcomes. More data are needed to characterize the safety profile of ustekinumab use during pregnancy.

Background and Aims Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis. We report integrated analyses of infections in the Phase [P]2 and P3 OCTAVE programmes. Methods Three cohorts were analysed: Induction [P2/3 induction studies]; Maintenance [P3 maintenance study]; and Overall [all tofacitinib-treated patients in induction, maintenance, or ongoing, open-label, long-term extension studies; as of May 2019]. Proportions and incidence rates [IRs; unique patients with events/100 patient-years] of serious infections [SIs], herpes zoster [HZ] [non-serious and serious], and opportunistic infections [OIs] are reported [censored at time of event]. Results In the Induction Cohort [N = 1220], no patients receiving placebo and eight [0.9%] receiving tofacitinib 10 mg twice daily [BID] developed SIs. Maintenance Cohort [N = 592] SI IRs (95% confidence interval [CI]) were 1.94 [0.23–7.00] for placebo and 1.35 [0.16–4.87] and 0.64 [0.02–3.54] for tofacitinib 5 and 10 mg BID, respectively; HZ IRs were 0.97 [0.02–5.42], 2.05 [0.42–6.00], and 6.64 [3.19–12.22], respectively. In the Overall Cohort [N = 1157; 82.9% predominantly received tofacitinib 10 mg BID], SI, HZ, and non-HZ OI IRs were 1.70 [1.24–2.27], 3.48 [2.79–4.30], and 0.15 [0.04–0.38], respectively. No SIs resulted in death. Conclusions During induction, SIs were more frequent with tofacitinib versus placebo. SIs were generally infrequent in the Maintenance and Overall Cohorts, with rates comparable between treatment groups. Maintenance Cohort HZ IR was numerically higher with tofacitinib 10 mg BID versus 5 mg BID. Overall Cohort HZ IRs remained stable over time. Non-HZ OIs and viral infections were rare.

While there is recent literature to support the discontinuation of 5-aminosalicylate (5-ASA) upon the initiation of biologics, continuing 5-ASA after treatment failure is relatively common. We aimed to assess the impact of concomitant 5-ASA therapy on clinical outcomes in ulcerative colitis (UC) patients escalated to infliximab. This is a retrospective chart review of patients with moderate-to-severe UC started on infliximab between January 2012 and December 2017 at the University of Alberta. The primary outcome was clinical remission (partial Mayo score

We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD).This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation.A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients.UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

BACKGROUND: Little is known about the consequences of intrauterine exposure to, and the post-natal clearance of, vedolizumab.AIMS: To investigate the levels of vedolizumab in umbilical cord blood of newborns and rates of clearance after birth, as well as how these correlated with maternal drug levels, risk of infection and developmental milestones during the first year of life METHODS: Vedolizumab-treated pregnant women with inflammatory bowel disease were prospectively recruited from 12 hospitals in Denmark and Canada in 2016-2020. Demographics were collected from medical records. Infant developmental milestones were evaluated by the Ages and Stages Questionnaire (ASQ-3). Vedolizumab levels were measured at delivery and, in infants, every third month until clearance. Non-linear regression analysis was applied to estimate clearance.RESULTS: In 50 vedolizumab-exposed pregnancies, we observed 43 (86%) live births, seven (14%) miscarriages, no congenital malformations and low risk of adverse pregnancy outcomes. Median infant:mother vedolizumab ratio at birth was 0.44 (95% confidence interval [CI], 0.32-0.56). The mean time to vedolizumab clearance in infants was 3.8 months (95% CI, 3.1-4.4). No infant had detectable levels of vedolizumab at 6 months of age. Developmental milestones at 12 months were normal or above average. Neither vedolizumab exposure in the third trimester (RR 0.54, 95% CI, 0.28-1.03) nor combination therapy with thiopurines (RR 1.29, 95% CI, 0.60-2.77) seemed to increase the risk of infections in the offspring.CONCLUSIONS: Neonatal vedolizumab clearance following intrauterine exposure is rapid. Infant vedolizumab levels did not correlate with the risk of infections during the first year of life. Continuation of vedolizumab throughout pregnancy is safe.

Background and aims This study examined differences in personality, psychological distress, and stress coping in inflammatory bowel disease (IBD) depending on type of disease and disease activity. We compared patients suffering from Crohn’s disease (CD) and ulcerative colitis (UC) with controls. While the literature is replete with distinctive features of the pathogenesis of IBD, the specific differences in psychological impairments are not well studied. Methods In this German national multicenter study, participants were recruited from 32 centers. Two hundred ninety-seven questionnaires were included, delivering vast information on disease status and psychological well-being based on validated instruments with a total of 285 variables. Results CD patients were more affected by psychological impairments than patients suffering from UC or controls. Importantly, patients with active CD scored higher in neuroticism (p Conclusions We identified specific aspects of psychological impairment in IBD depending on disease and disease activity. Our results underscore the need for psychological support and treatment particularly in active CD.

ispartof: JOURNAL OF CROHNS & COLITIS vol:13 issue:2 pages:144-+ ispartof: location:England status: published

While there is recent literature to support the discontinuation of 5-aminosalicylate (5-ASA) upon the initiation of biologics, continuing 5-ASA after treatment failure is relatively common. We aimed to assess the impact of concomitant 5-ASA therapy on clinical outcomes in ulcerative colitis (UC) patients escalated to infliximab.This is a retrospective chart review of patients with moderate-to-severe UC started on infliximab between January 2012 and December 2017 at the University of Alberta. The primary outcome was clinical remission (partial Mayo score 2) at 6 and 12 months. Secondary outcomes included endoscopic (endoscopic Mayo 2) and deep remission (combined clinical and endoscopic remission) as well as the need for rescue therapy, hospitalization or colectomy. Univariate and multivariate logistic regression models were used to estimate the odds ratios and 95% CI for the outcomes.One hundred and twenty-one patients were followed over a period of 47 (SD = 34) months. Patients on 5-ASA had increased concomitant immunomodulator use (73.3% vs. 54.1%, p = 0.03). There was no difference in clinical remission at 6 (aOR 2.59, p = 0.07) or 12 months (aOR 0.43, p = 0.06). At 12 months, patients on concomitant 5-ASA were less likely to achieve endoscopic (aOR 0.08, p = 0.01) and deep remission (aOR 0.07, p = 0.02). Adverse outcomes such as need for rescue therapy, hospitalization, and colectomy did not differ between the groups.Our data suggest that 5-ASA may be stopped in patients with moderate-to-severe UC who have been escalated to infliximab therapy as it has no additional benefit to control inflammation.

Perianal fistulizing Crohn's disease is associated with a poor quality of life and current medical and surgical treatment options are limited. Darvadstrocel, composed of mesenchymal stem (stromal) cells (MSC), has recently been approved by the European Medicines Agency (EMA) for the treatment for perianal disease. This drug profile educates the reader with this novel treatment approach.A literature search was performed on PubMed with focus on perianal fistulizing Crohn's disease and mesenchymal stem (stromal) cells. This review summarizes evidence of the current standard of care and discusses the mechanism of action, manufacturing, and application and safety of darvadstrocel.Darvadstrocel is a safe and effective therapy for complex perianal fistulizing Crohn's disease.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) pandemic is a worldwide emergency. An increasing number of diarrhea cases is reported. Here we investigate the epidemiology, clinical presentation, molecular mechanisms, management, and prevention of SARS-CoV-2 associated diarrhea. We searched on PubMed, EMBASE, and Web of Science up to March 2020 to identify studies documenting diarrhea and mechanism of intestinal inflammation in patients with confirmed diagnosis of SARS-CoV-2 infection. Clinical studies show an incidence rate of diarrhea ranging from 2% to 50% of cases. It may precede or trail respiratory symptoms. A pooled analysis revealed an overall percentage of diarrhea onset of 10.4%. SARS-CoV uses the angiotensin-converting enzyme 2 (ACE2) and the serine protease TMPRSS2 for S protein priming. ACE2 and TMPRSS2 are not only expressed in lung, but also in the small intestinal epithelia. ACE2 is expressed furthermore in the upper esophagus, liver, and colon. SARS-CoV-2 binding affinity to ACE2 is significantly higher (10-20 times) compared with SARS-CoV. Several reports indicate viral RNA shedding in stool detectable longer time period than in nasopharyngeal swabs. Current treatment is supportive, but several options appear promising and are the subject of investigation. Diarrhea is a frequent presenting symptom in patients infected with SARS-CoV-2. Increasing evidence indicates possible fecal oral transmission, indicating the need for a rapid and effective modification of the screening and diagnostic algorithms. The optimal methods to prevent, manage, and treat diarrhea in COVID-19 infected patients are subjects of intensive research.

Computerized clinical decision support systems, or CDSS, represent a paradigm shift in healthcare today. CDSS are used to augment clinicians in their complex decision-making processes. Since their first use in the 1980s, CDSS have seen a rapid evolution. They are now commonly administered through electronic medical records and other computerized clinical workflows, which has been facilitated by increasing global adoption of electronic medical records with advanced capabilities. Despite these advances, there remain unknowns regarding the effect CDSS have on the providers who use them, patient outcomes, and costs. There have been numerous published examples in the past decade(s) of CDSS success stories, but notable setbacks have also shown us that CDSS are not without risks. In this paper, we provide a state-of-the-art overview on the use of clinical decision support systems in medicine, including the different types, current use cases with proven efficacy, common pitfalls, and potential harms. We conclude with evidence-based recommendations for minimizing risk in CDSS design, implementation, evaluation, and maintenance.

Women with inflammatory bowel diseases (IBD) often receive biologicals during pregnancy to maintain disease remission. Data on outcome of vedolizumab-exposed pregnancies (VDZE) are sparse., info:eu-repo/semantics/published

Background: Psychological stress negatively impacts inflammatory bowel disease (IBD) outcomes. Patients have prioritized access to online interventions; yet, the data on these have been limited by mixed in-person/online interventions, low adherence, and non-randomized controlled trial (RCT) design. Objectives: We assessed the efficacy of and adherence to a 12-week online multicomponent stress reduction intervention in IBD. Design: This is a RCT. Methods: Adult participants on stable IBD medical therapy with elevated stress levels from four centers were randomized to intervention or control groups. Intervention participants received a 12-week online program including a weekly yoga, breathwork and meditation video (target 2–3 times/week), a weekly cognitive behavioral therapy/positive psychology informed video activity, and weekly 10-min check-ins by a study team member. Control participants received weekly motivational messages by email. All patients received standard of care IBD therapy. The primary outcome was Cohen’s Perceived Stress Scale (PSS). Secondary outcomes evaluated mental health, resilience, health-related quality of life (HRQoL), symptom indices, acceptability, adherence, and inflammatory biomarkers. Analysis of covariance was used to determine between-group differences. Results: Of 150 screened patients, 101 were randomized to the intervention ( n = 49) and control ( n = 52) groups (mean age: 42.5 ± 14.1 years; M:F 1:3, 48% with ulcerative colitis and 52% with Crohn’s disease). The between-group PSS improved by 22.4% (95% confidence interval, 10.5–34.3, p Conclusion: This 12-week online intervention improved perceived stress, mental health, and HRQoL, but did not impact IBD symptom indices or inflammatory biomarkers. The program was readily adopted and adhered to by participants with high retention rates. After iterative refinement based on participant feedback, future studies will evaluate the impact of a longer/more intense intervention on disease course. Registration: ClinicalTrials.gov Identifier NCT03831750 Plain Language Summary An online stress reduction intervention in inflammatory bowel disease patients improves stress, mental health, and quality of life People with inflammatory bowel disease (IBD) have high levels of stress, anxiety, and depression. Although IBD patients have expressed the need for online mental wellness interventions, the existing data to support these interventions in IBD are limited. In this trial, 101 IBD patients had the chance to participate in a 12-week online stress reduction intervention. In those patients randomly selected to participate in the online intervention, each week they received the following: a 20- to 30-min yoga, breathwork, and meditation video that they were asked to do 2–3 times a week, a 10- to 20-min mental wellness activity they were asked to do once during the week, and a 10-min telephone check-in with a study team member. Participants who were not selected to use the online intervention received a weekly motivational message by email. In all, 90 of the 101 participants (89%) completed the study with the mean age of participants being 43 years and the majority being females (75%). Ninety-one percent of participants who completed the intervention met the program target of doing the yoga, breathwork, and meditation video at least 2 times per week. Significant improvements were seen in perceived stress (by 22.4%), depression (by 29.5%), anxiety (by 23.7%), resilience (by 10.6%), and quality of life (by 8.9%). No changes were seen in IBD severity or in blood markers of inflammation. In conclusion, this study demonstrates evidence that a 12-week online stress reduction intervention had low dropout rates, high adherence and beneficial effects on stress, mental health, and quality of life measures. Continued feedback will be sought from study participants and our IBD patient partners to refine the intervention and assess the impact in future studies of patients with active IBD, as well as the impact of a longer/more intense intervention.

Purpose To measure in vivo liver stiffness by using US time-harmonic elastography in a cohort of pediatric patients who were overweight to extremely obese with nonalcoholic fatty liver disease (NAFLD) and to evaluate the diagnostic value of time-harmonic elastography for differentiating stages of fibrosis associated with progressive disease. Materials and Methods In this prospective study, 67 consecutive adolescents (age range, 10-17 years; mean body mass index, 34.7 kg/m

Background Active inflammatory bowel disease increases the risk of adverse pregnancy outcomes. Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). As a small molecule, tofacitinib is likely to cross the placental barrier; however, information on the effects of tofacitinib on pregnancy outcomes is limited. We report pregnancy and newborn outcomes among patients in UC clinical studies with prenatal (maternal/paternal) exposure to tofacitinib. Methods Pregnancies with maternal/paternal exposure to tofacitinib were identified and outcomes reported in 5 tofacitinib UC interventional studies (up to March 2017). Outcomes from tofacitinib rheumatoid arthritis (RA), psoriasis, and psoriatic arthritis interventional studies, and RA noninterventional postapproval safety studies, spontaneous adverse event reporting, and registry data are also reported. Results Of 1157 patients enrolled in the UC interventional studies, 301 were women of childbearing age. Eleven cases of maternal exposure and 14 cases of paternal exposure to tofacitinib (doses of 5 mg or 10 mg twice daily) before/at the time of conception or during pregnancy were identified. Outcomes included 15 healthy newborns, no fetal deaths, no neonatal deaths, no congenital malformations, 2 spontaneous abortions, and 2 medical terminations. Outcomes across other tofacitinib studies and postmarketing cases were consistent, with a healthy newborn being the most common outcome and no fetal deaths. Conclusions Based on the limited data available, pregnancy and newborn outcomes among patients with prenatal (maternal/paternal) exposure to tofacitinib in UC studies appear similar to those reported for other tofacitinib clinical study populations and the general population.

A summary of the First Signature Series Event, “Advancements in Cellular Therapies and Regenerative Medicine for Digestive Diseases,” held on May 3, 2017, in London, United Kingdom, is presented. Twelve speakers from three continents covered major topics in the areas of cellular therapy and regenerative medicine applied to liver and gastrointestinal medicine as well as to diabetes mellitus. Highlights from their presentations, together with an overview of the global impact of digestive diseases and a proposal for a shared online collection and data-monitoring platform tool, are included in this proceedings. Although growing evidence demonstrate the feasibility and safety of exploiting cell-based technologies for the treatment of digestive diseases, regulatory and methodological obstacles will need to be overcome before the successful implementation in the clinic of these novel attractive therapeutic strategies.