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Background and objective The influence of concomitant prednisolone on clinical outcomes and safety in infliximab-treated ulcerative colitis (UC) patients is unknown. Design, setting, participants and outcome measures A retrospective cohort study was performed, including 147 UC patients treated with infliximab at a tertiary inflammatory bowel disease (IBD) centre. Primary outcome was corticosteroid-free clinical remission (CFCR) at week 14 and week 52. Patients were grouped according to prednisolone tapering regimens: standard (≤5 mg/week), fast (>5 mg/week), direct discontinuation or no prednisolone. Patients intolerant to corticosteroids and patients stopping corticosteroids in preparation for surgery including colectomy during their initial admission were excluded. Results There was no overall association between prednisolone exposure or no exposure and CFCR at weeks 14 or 52 of infliximab. The proportion of patients with C reactive protein ≤5 mg/L was higher in the standard tapering at week 14 as compared with faster regimens or no prednisolone. In subgroup analyses, the standard tapering was associated with a higher rate of CFCR at week 14 compared with the fast-tapering regimen in patients receiving ≥40 mg prednisolone at initiation of infliximab (64.3% vs 26.3%, p=0.04) and among patients admitted with acute severe UC (66.6% vs 23.5%, p<0.05). Similar data were seen at week 52. Prednisolone did not affect infliximab trough levels but increased infection rates (10/77 vs 2/70, p=0.03), in particular C. difficile infection. Conclusion In UC patients with limited disease burden, prednisolone did not affect effectiveness of infliximab. However, patients with increased disease burden seem to benefit from corticosteroid combination therapy., Background and objective The influence of concomitant prednisolone on clinical outcomes and safety in infliximab-Treated ulcerative colitis (UC) patients is unknown. Design, setting, participants and outcome measures A retrospective cohort study was performed, including 147 UC patients treated with infliximab at a tertiary inflammatory bowel disease (IBD) centre. Primary outcome was corticosteroid-free clinical remission (CFCR) at week 14 and week 52. Patients were grouped according to prednisolone tapering regimens: standard (≤5 mg/ week), fast (>5 mg/week), direct discontinuation or no prednisolone. Patients intolerant to corticosteroids and patients stopping corticosteroids in preparation for surgery including colectomy during their initial admission were excluded. Results There was no overall association between prednisolone exposure or no exposure and CFCR at weeks 14 or 52 of infliximab. The proportion of patients with C reactive protein ≤5 mg/L was higher in the standard tapering at week 14 as compared with faster regimens or no prednisolone. In subgroup analyses, the standard tapering was associated with a higher rate of CFCR at week 14 compared with the fast-Tapering regimen in patients receiving ≥40 mg prednisolone at initiation of infliximab (64.3% vs 26.3%, p=0.04) and among patients admitted with acute severe UC (66.6% vs 23.5%, p<0.05). Similar data were seen at week 52. Prednisolone did not affect infliximab trough levels but increased infection rates (10/77 vs 2/70, p=0.03), in particular C. difficile infection. Conclusion In UC patients with limited disease burden, prednisolone did not affect effectiveness of infliximab. However, patients with increased disease burden seem to benefit from corticosteroid combination therapy.

Intestinal ultrasound (IUS) is non-invasive, fast, cheap, and well-tolerated and requires no preparation and is thus applicable as a point-of-care monitoring tool of inflammatory bowel disease (IBD). Evidence suggests that IUS is comparable to other standard monitoring modalities, i.e., endoscopy, MRI, calprotectin, and C-reactive protein and might be more accurate in predicting response to treatment at an early stage consequently allowing for timely optimised treatment. This review finds that integrating IUS as the standard of care in every IBD outpatient clinic and as the primary outcome in future medical trials seems inevitable.

Background and Aims: The association between cancer treatments and exacerbation of inflammatory bowel diseases [IBD] is unclear. We aimed to evaluate the effects of cancer treatments on the disease activity of IBD. Methods: We performed a systematic review of the literature on cancer therapy in patients with pre-existing IBD. Electronic searches of PubMed, Cochrane Library and Embase were combined with manual searches (September 2021). Meta-analysis was performed using the random-effects model. The primary outcome was flares of IBD following cancer therapy. Secondary outcomes were need for IBD-related hospitalization, surgery, and initiation or intensification of steroid or biological treatments to manage IBD flares. Results: In total, 33 studies were included in the systematic review, comprising 1298 patients with IBD who received cancer treatment. The overall occurrence of IBD flares following cancer treatment was 30% (95% confidence interval [CI] 23-37%). IBD flares resulted in utilization of systemic steroids and biologic therapies among 25% and 10% of patients, respectively, and in discontinuation of cancer treatment among 14% of patients. Finally, the risk of gastrointestinal toxicity following immune check point inhibitor treatment [ICI] was increased in patients with IBD compared to patients without IBD (RR = 3.62 [95% CI 2.57-5.09]). Despite this, the studies generally reported that flares were manageable. Conclusions: Current data indicate a high proportion of patients with IBD experiencing a flare following the start of cancer treatment. Patients with IBD were at an increased risk of gastrointestinal toxicity following ICI treatment compared to those without IBD. However, cancer therapy-induced IBD flares were manageable and should not preclude appropriate cancer treatments.

BACKGROUND: Tofacitinib has emerged as a new potential treatment for acute severe ulcerative colitis (ASUC). We conducted a systematic review to assess efficacy, safety, and integration in ASUC algorithms.METHODS: Systematic search in MEDLINE, EMBASE, Cochrane Library, and Clinicaltrials.gov until August 17, 2022, including all studies reporting original observations on tofacitinib for ASUC, preferably defined according to Truelove and Witts criteria. Primary outcome was colectomy-free survival.RESULTS: Of 1,072 publications identified, 21 studies were included of which three were ongoing clinical trials. The remaining comprised a pooled cohort originating from 15 case publications (n=42), a GETAID cohort study (n=55), a case-control study (n=40 cases), and a pediatric cohort (n=11). Of these 148 reported cases, tofacitinib was used as second line treatment after steroid failure in previous infliximab failures or third line after sequential steroid and infliximab or cyclosporine failure, 69 (47%) were female, age median ranged 17-34 years, disease duration 0.7-10 years. Overall, 30-day colectomy-free survival was 85% (n=123 of 145; n=3 without colectomy had follow-up <30 days), 90-day 86% (n=113 of 132; n=16 follow-up <90 days), and 180-day 69% (n=77 of 112; n=36 follow-up <180 days). Tofacitinib persistence at follow-up was 68-91%, clinical remission 35-69%, and endoscopic remission 55% reported. Adverse events occurred in 22 patients, predominantly being infectious complications other than herpes zoster (n=13), and resulted in tofacitinib discontinuation in seven patients.CONCLUSION: Tofacitinib appears promising for treatment of ASUC with high short-term colectomy-free survival among refractory patients otherwise deemed for colectomy. However, large high-quality studies are needed.

BACKGROUND AND AIMS: Few studies have assessed the contemporary patterns of disease activity in patients with inflammatory bowel disease (IBD). We aimed to describe the disease patterns and their long-term outcomes.METHODS: All Danish individuals with IBD between 1995 and 2018 were identified using information about IBD-related hospitalizations, surgeries, and redeemed prescriptions. The disease activity patterns for 5- and 10-year periods were assessed.RESULTS: In incident patients with Crohn's disease (CD), severe disease activity occurred in the year of diagnosis in 80% of patients; for ulcerative colitis (UC) this figure was 75%, in addition to 3.4% of UC patients who underwent a colectomy within the first year. After 20 years of disease, the proportion of CD and UC patients in remission increased to 89% and 72%, respectively. The proportion of prevalent patients in remission each year was stable, despite the introduction of biological therapies. A decreasing activity pattern was the most common in both CD and UC patients (both 45%). The distribution of the disease activity patterns was observed to be stable over time. A quiescent disease pattern was accompanied by a significantly higher risk of intestinal cancer (HR: 3.37, 95%CI: 1.23-9.19) for CD patients, according to a Cox proportional hazards model. In UC patients, increasing disease activity (HR: 0.67, 95%CI: 0.31-1.48) was associated with an increased risk of intestinal cancer.CONCLUSIONS: We reported the distribution of disease patterns among IBD patients. Patients with quiescent CD, as well as UC patients with chronic continuous or increasing activity, were at increased risk of developing intestinal cancer.

Background: Cancer patients treated with immune check point inhibitors are at risk of developing severe colitis. However, the efficacy and safety of treatment of severe colitis is poorly understood. Aims: To explore the safety and efficacy of infliximab and corticosteroids in severe immune-mediated enterocolitis (IMC). Method: We performed a nationwide retrospective cohort study on 140 cancer patients treated with infliximab due to IMC in Denmark from 2011 to 2021. Results: The rate of complete remission with infliximab was 52% after one dose, increasing to 73% after two or more doses. Thirteen patients (10%) required additional treatment with vedolizumab. Patients were heavily exposed to corticosteroids and received a median accumulated dose of 3978 mg (interquartile range [IQR] 2552–6414). Age- and cancer-adjusted Cox regression analysis found that a high dose of prednisolone at start of tapering ≥75 mg/day was associated with increased mortality (HR 1.67, 1.04–2.69, p = 0.035). Patients responding to infliximab experienced an improvement of symptoms after 3 days (IQR 2–4) and complete remission after 31 days (IQR 14–61). Twenty-four percent required hospitalisation for infection during treatment for IMC, lasting 7 days (median). Secondary gastrointestinal infections occurred in 16%, with Clostridioides difficile being most common (64%). Further, 10% had a thromboembolic event during the first 90 days after infliximab treatment. Conclusions: Infliximab led to complete resolution of symptoms in 73% of patients with IMC. High prednisolone dose at tapering was associated with increased mortality rate and a high incidence of infections and hospitalisations in patients with severe IMC. We suggest optimised infliximab treatment before escalation of steroid doses.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can induce a wide range of immune-related adverse events (irAEs), potentially affecting any organ. ICI-induced colitis is a frequently reported irAE, whereas enteritis is rare and not well documented.CASE PRESENTATION: We are presenting a patient with metastatic melanoma who developed severe ICI-induced enterocolitis multirefractory for glucocorticoids, infliximab and vedolizumab, partially responding to faecal microbiota transplantation and final complete response to tofacitinib.CONCLUSION: This case supports that tofacitinib may be an(other) effective agent in managing multirefractory ICI-induced diarrhoea caused by colitis and/or enteritis.

This brief report investigated the impact of clinical, biochemical, and endoscopic activity of IBD on the severity and long-term outcomes of COVID-19 in a prospective population-based cohort. The study did not identify any association between IBD activity and COVID-19 outcomes.

BACKGROUND AND AIMS: Our aim was to determine if transabdominal intestinal ultrasound changes after 48±24h of intravenous corticosteroids can predict treatment outcomes in hospitalized patients with severe ulcerative colitis.METHODS: We performed a blinded observational multicenter study. Ultrasound parameters were assessed before treatment initiation, after 48±24h, and 6±1 days. Treatment response was determined within seven days by two outcome measures: 1) Partial Mayo score reduction, 2) No administration of rescue therapy.RESULTS: Out of sixty-nine recruited patients, fifty-six were included in the final analysis, with thirty-seven responders. The colon segment with the highest baseline bowel wall thickness was analyzed, being the sigmoid in all patients. There was no difference in baseline bowel wall thickness between responders and non-responders in the partial Mayo score outcome. At 48±24h, a significant difference between responders and non-responders was identified in both absolute bowel wall thickness (median 3.1mm vs 4.9mm; p<0.0001), absolute reduction (-1.9mm vs -0.2mm; p<0.001), and relative reduction (-35.9% vs -4.1%; p<0.0001). A ≤20% reduction had a sensitivity of 84.2% (95%CI 60.4, 96.6%) and a specificity of 78.4% (61.8, 90.2%) for determining non-response (area under the curve 0.85). In the multivariable analysis, a >20% reduction had the highest odds ratio (22.6 (4.2, 201.2), p=0.001) for determining response. Similar results were seen for the rescue therapy outcome.CONCLUSIONS: Changes in bowel wall thickness after 48±24h following intravenous corticosteroid treatment in hospitalized patients with severe ulcerative colitis identify responders with high accuracy and might be used as an early marker to guide accelerated rescue therapy.

BACKGROUND: It is unclear whether inflammatory bowel diseases (IBDs) affect the phenotype and severity of co-occurring immune-mediated inflammatory diseases (IMIDs). We aimed to investigate the characteristics of IMIDs in relation to co-occurring IBD.METHODS: We conducted a systematic review of Medline and EMBASE databases from inception to September 2020. We identified studies reporting the phenotype, severity, or disease course of IMIDs among patients with or without co-occurring IBD. A meta-analysis was conducted using random effects models.RESULTS: The electronic search yielded 13 220 studies that we narrowed down to 73 eligible studies for full-text review, including 42 on primary sclerosing cholangitis, 12 on axial spondyloarthropathies, and 8 studies on psoriasis. In primary sclerosing cholangitis, IBD was associated with less frequent involvement of extrahepatic bile ducts (risk ratio [RR], 0.50; 95% confidence interval [CI], 0.33-0.75), longer liver transplantation-free survival (hazard ratio, 0.70; 95% CI, 0.60-0.82), and no increased risk of cholangiocarcinoma (RR, 0.88; 95% CI, 0.59-1.31). Patients with axial spondyloarthropathies and co-occurring IBD were characterized by an increased risk of dactylitis (RR, 2.06; 95% CI, 1.24-3.42), a lower Bath Ankylosing Spondylitis Radiology Index (mean difference [MD] = -2.28; 95% CI, -3.26 to -1.30), and better Schober's test results (MD = 1.07; 95% CI, 0.64-1.49). Psoriasis and co-occurring IBD was associated with reduced disease severity (RR, 1.41; 95% CI, 1.02-1.96) and less frequent presentation in nails (RR, 0.14; 95% CI, 0.05-0.42), with no apparent impact on psoriatic arthritis (RR, 0.94; 95% CI, 0.27-3.31).CONCLUSIONS: This systematic review with meta-analysis found IBD is associated with a distinct disease phenotype among the IMIDs investigated. Our findings emphasize the importance of multidisciplinary approaches to patients with co-occurring IMIDs and IBD.

BACKGROUND AND AIMS: The health consequences of the coronavirus disease 2019 (COVID-19) among patients with ulcerative colitis (UC) and Crohn's disease (CD) remain largely unknown. We aimed to investigate outcomes and long-term effects of COVID-19 in patients with UC or CD.METHODS: We conducted a prospective, population-based study covering all Danish patients with CD or UC and confirmed COVID-19 between January 28th, 2020 and April 1st, 2021, through medical records and questionnaires.RESULTS: All 319 patients with UC and 197 patients with CD who developed COVID-19 in Denmark were included in this study and compared with the Danish background population with COVID-19 (N=230,087). A significantly higher risk of COVID-19-related hospitalization was observed among patients with UC (N=46(14.4%), RR=2.49 (95%CI 1.91-3.26)) and CD (N=24(12.2%), RR=2.11 (95%CI 1.45-3.07)) as compared with the background population (N=13,306 (5.8%)). A similar pattern was observed for admission to intensive care (UC: N=8(2.51%), RR=27.88 (95%CI 13.88-56.00); CD: N=3 (1.52%), RR=16.92 (95%CI 5.46-52.46)). After a median of 5.1 months (IQR 4.5-7.9), 58 (42.3%) and 39 (45.9%) patients with UC and CD, reported persisting symptoms which were independently associated with discontinuation of immunosuppressive therapies during COVID-19 (OR=1.50 (95%CI 1.07-10.22), p=0.01) and severe COVID-19 (OR=2.76 (95%CI 1.05-3.90), p=0.04), but not with age nor presence of comorbidities.CONCLUSION: In this population-based study of 516 patients with IBD and COVID-19, 13.6% needed hospitalization and 2.1% required intensive care. Furthermore, sequelae were frequent affecting 43.7% of COVID-19 infected. These findings might have implications for planning the healthcare of patients in the post-COVID-19 era.

Improving the long-term prognosis of ulcerative colitis (UC) requires sustained deep mucosal colonic healing with histologic remission, making the study of colonic tissue regeneration essential. In experimental colitis models, lipid metabolites are recognized as pivotal components of this process. This study aimed to describe the kinetics of wound healing and lipid metabolites engaged in regeneration in the normal colonic mucosa and how they are affected in UC to reveal new therapeutic targets. Experimental colonic wounds were created endoscopically in quiescent UC (n=21) and controls (n=9), and the healing process was surveilled by serial endoscopies and cross-sectional wound biopsies post-wounding. Biopsies were analyzed by liquid chromatography coupled with mass spectrometry. Endoscopic wound scores were significantly higher in UC at day two (p=0.001) and seven (p<0.0001) post-wounding, demonstrating a prolonged wound healing process. The wound scores were correlated with lipid mediators crucial for normal regeneration and sustained UC-specific changes in key phospholipids and eicosanoids, i.e., lysophosphatidylcholine, phosphatidylcholine, lysophosphatidic acid, phosphatidylglycerol, phosphatidylinositol, prostaglandin D2, and prostaglandin E1, were observed. A prolonged wound healing process is identified in quiescent UC with altered disease specific lipidomic trajectories providing potential novel therapeutic avenues for stimulating mucosal regeneration as an add-on to the traditional immune suppression treatment.

BACKGROUND AND AIMS: The trigger hypothesis opens the possibility of anti-flare-initiation therapies by stating that ulcerative colitis (UC) flares originates from inadequate responses to acute mucosal injuries. However, experimental evidence is restricted by a limited use of suitable human models. We thus aimed to investigate the acute mucosal barrier injury responses in humans with and without UC using an experimental injury model.METHODS: A standardized mucosal break was inflicted in the sigmoid colon of 19 patients with UC in endoscopic and histological remission and 20 control subjects. Post-injury responses were assessed repeatedly by high resolution imaging and sampling to perform Geboes scoring, RNA sequencing, and injury niche microbiota 16S rRNA gene sequencing.RESULTS: UC patients had more severe endoscopic post-injury inflammation than controls (p<0.01), an elevated modified Geboes score (p<0.05), a rapid induction of innate response gene sets (p<0.05) and anti-microbial peptides (p<0.01), and engagement of neutrophils (p<0.01). Innate lymphoid cells type 3 (ILC3s) markers were increased pre-injury (p<0.01) and ILC3 activating cytokines were highly induced post-injury resulting in an increase in ILC3 type cytokine IL-17A. Across groups, the post-injury mucosal microbiome had higher bacterial load (p<0.0001) and lower α-diversity (p<0.05).CONCLUSIONS: UC patients in remission respond to mucosal breaks by an innate hyper-response engaging resident regulatory ILC3s and a subsequent adaptive activation. The post-injury IBD-like microbiota diversity decrease is irrespective of diagnosis suggesting that the dysbiosis is secondary to host injury responses. We provide a model for the study of flare initiation in the search for anti-trigger directed therapies.