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Background and Aims: COVID-19 vaccination prevents severe disease in most patients with inflammatory bowel disease (IBD), but immunosuppressive medications can blunt serologic response. We followed adults with IBD for >1 year post-COVID-19 vaccination to describe factors associated with SARS-CoV-2 infection after vaccination, evaluate for a protective SARS-CoV-2 antibody level, characterize SARS-CoV-2 antibody persistence, and identify factors associated with humoral immune response durability., Methods: Using a prospective cohort of COVID-19 immunized adults with IBD, we analyzed factors associated with SARS-CoV-2 infection after vaccination. We evaluated for an association between SARS-CoV-2 antibody level 12 weeks postvaccination and subsequent SARS-CoV-2 infection and assessed for a threshold of protection using receiver-operating characteristic curve analysis. We then conducted a separate analysis evaluating factors associated with persistence of SARS-CoV-2 antibodies 52 weeks postimmunization., Results: Almost half (43%) of 1869 participants developed COVID-19 after vaccination, but most infections were mild, and <1% required hospitalization. Older age and corticosteroid use were associated with a decreased risk of SARS-CoV-2 infection postvaccination (50-59 years of age vs 18-29 years of age: adjusted hazard ratio, 0.57; 95% confidence interval, 0.44-0.74; steroid users vs nonusers: adjusted hazard ratio, 0.58; 95% confidence interval, 0.39-0.87). Most (98%) participants had detectable antibody levels at 52 weeks postvaccination. Antibody levels at 12 weeks and number of vaccine doses were positively associated with higher antibody levels at 52 weeks, while anti-tumor necrosis factor α therapy was negatively associated., Conclusions: COVID-19 vaccination generates an effective and durable protective response for the vast majority of adults with IBD, including vulnerable populations such as corticosteroid users and older individuals. Patients with IBD benefit from COVID-19 booster vaccination., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: Computerized-adaptive testing (CAT) may increase reliability or reduce respondent burden for assessing patient-reported outcomes compared with static short forms (SFs). We compared CAT versus SF administration of the Patient-Reported Outcomes Measurement Information System® (PROMIS®) Pediatric measures in pediatric inflammatory bowel disease (IBD)., Methods: Participants completed 4-item CAT, 5- or 6-item CAT, and 4-item SF versions of the PROMIS Pediatric measures. We compared average T-scores, intra-class correlations (ICCs), floor and ceiling effects, and standard error of measurement (SEM) across forms, along with mean effect sizes between active versus quiescent IBD disease activity groups., Results: Average PROMIS T-scores across forms were <3 points (minimally important difference) of each other. All forms correlated highly with each other (ICCs ≥0.90) and had similar ceiling effects, but the CAT-5/6 had lower floor effects. The CAT-5/6 had lower SEM than the CAT-4 and SF-4, and the CAT-4 had a lower SEM than the SF-4. Mean effect sizes were similar across forms when contrasting disease activity groups., Conclusions: The CAT and SF forms produced similar score results, but the CAT had better precision and lower floor effects. Researchers should consider PROMIS pediatric CAT if they anticipate that their sample will skew toward symptom extremes., Competing Interests: The authors have no competing interests to declare., (© The Author(s) 2023.)

Background: Medication adherence impacts disease control in inflammatory bowel disease (IBD). Existing adherence measures such as the Morisky Medication Adherence Scale 8 © are often costly, non-medication-specific, and time-consuming., Aims: We aimed to develop a non-proprietary, IBD-specific medication adherence instrument and to assess reasons for suboptimal medication adherence., Methods: We developed the IBD Medication Adherence Tool to assess frequency of adherence and indications for missed or delayed medication doses. We co-administered the IBD Medication Adherence Tool and the Morisky Medication Adherence Scale 8 © (licensed for use) to participants enrolled in an internet-based cohort of adults with IBD and taking least one daily, oral IBD medication. We used Spearman's correlation to evaluate associations between the IBD Medication Adherence Tool and Morisky Medication Adherence Scale 8 © . We then categorized patients as sub-optimally adherent (IBD Medication Adherence Tool score 1-4) and highly adherent (score 5) and evaluated factors associated with and reasons for suboptimal adherence using multivariable analysis., Results: We evaluated 514 patients (73% female, mean age 49), of whom 21.4% had suboptimal adherence. IBD Medication Adherence Tool scores were moderately correlated with Morisky Medication Adherence Scale 8 © (r = 0.56, p < 0.001). The most commonly reported reasons for suboptimal adherence were forgetting, feeling well, and cost. Younger age and current smoking were associated with suboptimal adherence., Conclusions: We developed a non-proprietary, IBD-specific tool to assess adherence to IBD medications, validated in a cohort of patients with IBD on daily, oral medications. Common reasons for suboptimal IBD medication adherence include forgetting, feeling well, and cost., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Cases of coronavirus disease 2019 (COVID-19) have emerged in discrete waves. We explored temporal trends in the reporting of COVID-19 in inflammatory bowel disease (IBD) patients., Methods: The Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is an international registry of IBD patients diagnosed with COVID-19. The average percent changes (APCs) were calculated in weekly reported cases of COVID-19 during the periods of March 22 to September 12, September 13 to December 12, 2020, and December 13 to July 31, 2021., Results: Across 73 countries, 6404 cases of COVID-19 were reported in IBD patients. COVID-19 reporting decreased globally by 4.2% per week (95% CI, -5.3% to -3.0%) from March 22 to September 12, 2020, then climbed by 10.2% per week (95% CI, 8.1%-12.3%) from September 13 to December 12, 2020, and then declined by 6.3% per week (95% CI, -7.8% to -4.7%). In the fall of 2020, weekly reporting climbed in North America (APC, 11.3%; 95% CI, 8.8-13.8) and Europe (APC, 17.7%; 95% CI, 12.1%-23.5%), whereas reporting was stable in Asia (APC, -8.1%; 95% CI, -15.6-0.1). From December 13, 2020, to July 31, 2021, reporting of COVID-19 in those with IBD declined in North America (APC, -8.5%; 95% CI, -10.2 to -6.7) and Europe (APC, -5.4%; 95% CI, -7.2 to -3.6) and was stable in Latin America (APC, -1.5%; 95% CI, -3.5% to 0.6%)., Conclusions: Temporal trends in reporting of COVID-19 in those with IBD are consistent with the epidemiological patterns COVID-19 globally., (© 2022 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background and Aims: Age is a major prognostic factor for COVID-19 outcomes. The effect of inflammatory bowel disease [IBD] activity on COVID-19 is unclear. We examined the relationship between IBD activity and COVID-19 severity according to age., Methods: We included IBD patients diagnosed with COVID-19, reported to SECURE-IBD between March 13, 2020 and August 3, 2021. Clinical IBD activity was measured by physician global assessment [PGA]. COVID-19-related outcomes were [1] intensive care unit [ICU] admission, ventilation or death, and [2] hospitalization. Using generalized estimating equations, we determined adjusted odds ratios [aOR, 95% confidence interval] for moderate and severe PGA vs clinical remission/mild PGA, controlling for demographics, medications and COVID-19 diagnosis period. We performed stratified analyses by age [≤50 vs >50 years]., Results: Among 6078 patients, adverse COVID-19 outcomes were more common with active IBD: ICU/ventilation/death in 3.6% [175/4898] of remission/mild, 4.9% [45/920] of moderate and 8.8% [23/260] of severe [p < 0.001]; and hospitalization in 13% [649/4898] of remission/mild, 19% [178/920] of moderate and 38% [100/260] of severe [p < 0.001]. Stratified by decade, effect sizes were larger for younger patients. In patients ≤50 years, severe PGA was independently associated with ICU/ventilation/death (aOR 3.27 [1.15-9.30]) and hospitalization (aOR 4.62 [2.83-7.55]). In contrast, severe PGA was not independently associated with COVID-19 outcomes in those older than 50 years., Conclusions: Clinically active IBD may be a risk factor for severe COVID-19, particularly in younger patients. IBD disease control, including through medication compliance, and strategies to mitigate the risk of COVID-19 infection amongst patients with active IBD [e.g. distancing, immunization] are key to limit adverse COVID-19 outcomes., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Studies of adults with Crohn's disease (CD) suggest that poor mental health precedes worsening disease activity. We evaluated whether depression and/or anxiety forecast worsening pediatric CD disease activity., Methods: Through the Inflammatory Bowel Disease Partners Kids & Teens internet-based cohort, children with CD age 9 to 17 completed Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric measures and the short Crohn's disease activity index (sCDAI). Using general linear models, we examined how baseline PROMIS Pediatric anxiety and depressive symptom scores independently associate with subsequent sCDAI scores (average survey interval 6.4 months). Models included baseline PROMIS Pediatric anxiety and depressive symptoms scores, baseline sCDAI, sex, age, parental education, race/ethnicity, and prior IBD-related surgery. We performed a post hoc subanalysis of children in baseline remission (sCDAI <150) with otherwise identical models., Results: We analyzed 159 children with CD (mean age 14 years, 45% female, 84% in baseline remission). We found no association between baseline PROMIS Pediatric anxiety score and subsequent sCDAI (change in sCDAI for 3-point change in PROMIS Pediatric -0.89; 95% CI -4.81 to 3.03). Baseline PROMIS Pediatric depressive symptoms score was not associated with future sCDAI (change in sCDAI for 3-point change in PROMIS Pediatric <0.01; 95% CI -4.54 to 4.53). In a subanalysis of patients in remission at baseline, the lack of association remained., Conclusion: We found that neither anxiety nor depressive symptoms associate with subsequent disease activity in pediatric CD. These findings contrast with adult IBD studies, thus underschoring the unique pathophysiology, natural history, and outcomes of pediatric CD., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Comorbidities increase the risk of coronavirus disease 2019 (COVID-19) hospitalization and mortality. As many comorbidities are common in patients with inflammatory bowel diseases (IBD), we sought to investigate the effects of comorbidities in these patients on infection severity., Aim: To evaluate association between individual comorbidities and COVID-19 infection severity among patients with IBD., Methods: Data were obtained from SECURE-IBD, an international registry created to evaluate COVID-19 outcomes in patients with IBD. We used multivariable regression to analyze associations between eleven non-IBD comorbidities and a composite primary outcome of COVID-19-related hospitalization or death. Comorbidities were first modeled individually, adjusting for potential confounders. Next, to determine the independent effect of comorbidities, we fit a model including all comorbidities as covariates., Results: We analyzed 2,035 patients from 58 countries (mean age 42.7 years, 50.6% male). A total of 538 patients (26.4%) experienced severe COVID-19. All comorbidities but a history of stroke and obesity were associated with severe infection in our initial analysis, with adjusted odds ratios ranging from 1.9 to 3.7. In a model including all comorbidities significantly associated with the composite outcome in the initial analysis, as well as other confounders, most comorbidities remained significant, with the highest risk in chronic kidney disease and chronic obstructive pulmonary disease., Conclusion: Many non-IBD comorbidities are associated with a two to threefold increased risk of COVID-19 hospitalization or death among patients with IBD. These data can be used to risk-stratify and guide treatment and lifestyle decisions during the ongoing pandemic., (© 2021. The Author(s).)

Background: Patients with inflammatory bowel disease (IBD) often require the use of immunosuppressant medications that increase infection risk, leading to concerns over the safe use of IBD medications during the Coronavirus 19 (COVID-19) pandemic., Objectives: To summarize available evidence on the safety and appropriate use of IBD medications during the COVID-19 pandemic, particularly in regard to risk of severe COVID-19 outcomes such as hospitalization, respiratory failure, or death for patients on IBD therapeutics., Conclusions: The majority of IBD medications are safe to continue during the COVID-19 pandemic, with a few notable exceptions. Patients with IBD who do not have COVID-19 should continue their prescribed IBD therapies, although steroids are associated with severe COVID-19 outcomes and should be weaned when possible. Corticosteroids should be tapered and discontinued when possible in patients with IBD who test positive for COVID-19 as well. Patients with IBD who test positive for COVID-19 should hold biologics, thiopurines, methotrexate, and tofacitinib for at least 2 weeks, and those who have symptoms should not restart these medications until symptom resolution. During the COVID-19 pandemic, all patients with IBD should continue to follow public health guidance including social distancing, masking, and COVID-19 vaccination recommendations., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Kamath and Dr. Brenner report no conflict of interest. Dr Brenner is supported by a T32 training grant from the 10.13039/100000002National Institutes of Health (grant number T32 DK007634)., (© 2022 The Authors.)

Objectives: Develop an individualised prognostic risk prediction tool for predicting the probability of adverse COVID-19 outcomes in patients with inflammatory bowel disease (IBD)., Design and Setting: This study developed and validated prognostic penalised logistic regression models using reports to the international Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease voluntary registry from March to October 2020. Model development was done using a training data set (85% of cases reported 13 March-15 September 2020), and model validation was conducted using a test data set (the remaining 15% of cases plus all cases reported 16 September-20 October 2020)., Participants: We included 2709 cases from 59 countries (mean age 41.2 years (SD 18), 50.2% male). All submitted cases after removing duplicates were included., Primary and Secondary Outcome Measures: COVID-19 related: (1) Hospitalisation+: composite outcome of hospitalisation, ICU admission, mechanical ventilation or death; (2) Intensive Care Unit+ (ICU+): composite outcome of ICU admission, mechanical ventilation or death; (3) Death. We assessed the resulting models' discrimination using the area under the curve of the receiver operator characteristic curves and reported the corresponding 95% CIs., Results: Of the submitted cases, a total of 633 (24%) were hospitalised, 137 (5%) were admitted to the ICU or intubated and 69 (3%) died. 2009 patients comprised the training set and 700 the test set. The models demonstrated excellent discrimination, with a test set area under the curve (95% CI) of 0.79 (0.75 to 0.83) for Hospitalisation+, 0.88 (0.82 to 0.95) for ICU+ and 0.94 (0.89 to 0.99) for Death. Age, comorbidities, corticosteroid use and male gender were associated with a higher risk of death, while the use of biological therapies was associated with a lower risk., Conclusions: Prognostic models can effectively predict who is at higher risk for COVID-19-related adverse outcomes in a population of patients with IBD. A free online risk calculator (https://covidibd.org/covid-19-risk-calculator/) is available for healthcare providers to facilitate discussion of risks due to COVID-19 with patients with IBD., Competing Interests: Competing interests: JS, KSS, ML, XZ, EJB, MA and MRK report no conflicts of interest. RU has served as a consultant and/or advisory board member for Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer and Takeda. He has received research support from AbbVie, Boehringer Ingelheim and Pfizer. He is supported by a Career Development Award from the National Institutes of Health (K23KD111995‐01A1). J-FC reports receiving research grants from AbbVie, Janssen Pharmaceuticals and Takeda; receiving payment for lectures from AbbVie, Amgen, Allergan, Inc. Ferring Pharmaceuticals, Shire and Takeda; receiving consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene Corporation, Celltrion, Eli Lilly, Enterome, Ferring Pharmaceuticals, Genentech, Janssen Pharmaceuticals, Landos, Ipsen, Medimmune, Merck, Novartis, Pfizer, Shire, Takeda, Tigenix, Viela bio; and hold stock options in Intestinal Biotech Development and Genfit. MK has consulted for Abbvie, Janssen, Pfizer and Takeda, is a shareholder in Johnson & Johnson, and has received research support from Pfizer, Takeda, Janssen, Abbvie, Lilly, Genentech, Boehringer Ingelheim, Bristol Myers Squibb, Celtrion and Arenapharm., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The impact of immune-modifying therapies on outcomes of coronavirus disease 2019 [COVID-19] is variable. The purpose of this study was to determine the impact of vedolizumab [VDZ], a gut-selective anti-integrin, on COVID-19 outcomes in inflammatory bowel disease [IBD] patients., Methods: Using data from the Surveillance of Coronavirus Under Research Exclusion for IBD [SECURE-IBD], an international registry of IBD patients with confirmed COVID-19, we studied the impact of VDZ on COVID-19 hospitalization and severe COVID-19 [intensive care unit stay, mechanical ventilation and/or death]., Results: Of 3647 adult patients on any IBD medication in the registry, 457 [12.5%] patients were on VDZ. On multivariable analyses using backward selection of covariates, VDZ use was not associated with hospitalization or severe COVID-19 when compared with patients on all other medications (adjusted odds ratio [aOR] 0.87; 95% confidence interval [CI] 0.71, 1.1 and aOR 0.95; 95% CI 0.53, 1.73, respectively). On comparing VDZ monotherapy to anti-tumour necrosis factor [anti-TNF] monotherapy, the odds for hospitalization, but not severe COVID-19, were higher [aOR CI 1.39; 95% CI 1.001, 1.90 and aOR 2.92; 95% CI 0.98, 8.71, respectively]. In an exploratory analysis, VDZ monotherapy, compared to anti-TNF monotherapy, was associated with new-onset gastrointestinal symptoms at the time of COVID-19, especially among patients whose IBD was in remission., Conclusions: COVID-19 outcomes among IBD patients on VDZ are comparable to those on all other therapies. Hospitalization, but not severe COVID-19, is more likely with VDZ monotherapy than with anti-TNF monotherapy. Overall, VDZ appears to be safe in IBD patients with COVID-19., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Importance: Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood., Objective: To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19-associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs., Design, Setting, and Participants: This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age ≥18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included., Exposures: Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy., Main Outcomes and Measures: The main outcome was COVID-19-associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations., Results: A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P < .001), and Jak inhibitor monotherapy (OR, 1.82; 95% CI, 1.21-2.73; P = .004) but not among those who received a TNF inhibitor in combination with methotrexate therapy (OR, 1.18; 95% CI, 0.85-1.63; P = .33). Similar findings were obtained in analyses that accounted for potential reporting bias and sensitivity analyses that excluded patients with a COVID-19 diagnosis based on symptoms alone., Conclusions and Relevance: In this cohort study, TNF inhibitor monotherapy was associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory treatment regimens among individuals with IMIDs.

The coronavirus disease 2019 (COVID-19) has affected more than 29 million people and led to more than 542,000 deaths in the United States. 1 Older age, comorbidities, and racial and ethnic minority status are associated with severe COVID-19. 2 Among patients with inflammatory bowel disease (IBD), racial and ethnic minorities have worse outcomes, mediated in part by inequitable health care access. 3 Racial and ethnic minority patients with IBD and COVID-19 may be an especially vulnerable population. The purpose of this study was to evaluate racial and ethnic disparities in COVID-19 outcomes among IBD patients and the impact of non-IBD comorbidities on observed disparities., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Gastric and duodenal mucosa may appear normal in eosinophilic gastroenteritis (EGE). Adult gastroenterologists typically biopsy only in the setting of mucosal abnormalities or symptoms, while pediatric providers biopsy all patients. The biopsy yield of EGE has not been adequately evaluated., Aims: To evaluate the biopsy yield of EGE in a pediatric cohort and assess predictors of increased biopsy yield., Methods: We identified patients age 0-18 who underwent upper endoscopy. We recorded endoscopic findings, pathology, demographics, and clinical and laboratory characteristics. We identified EGE cases (>20 eosinophils per high-power field on stomach and/or duodenum biopsy). We compared characteristics between EGE and non-EGE cases, calculated biopsy diagnostic yield, and performed multivariate analysis for predictors of increased biopsy yield., Results: In 509 patients (55.6% female, mean age 10.3 years, 69.7% white, 58.7% atopic), biopsy diagnostic yield for EGE was 1.2% (6/509) among all subjects, 7.7% (3/39) for those with peripheral eosinophilia (≥500 eos/uL), 9.1% (3/33) for those with hypoalbuminemia (<3.5 g/dL), and 25.0% (3/12) for those with peripheral eosinophilia and hypoalbuminemia. The odds of EGE were 27.8 (95% CI 3.3-231.8) times greater among those with peripheral eosinophilia. The mean total biopsy surface area and number of fragments was similar between patients with and without EGE. The area under the ROC curve for blood eosinophil counts and albumin level for predicting EGE was 0.926., Conclusions: The biopsy diagnostic yield for EGE is low but increases with peripheral eosinophilia and hypoalbuminemia. Patients with these features should have biopsies obtained, regardless of endoscopic appearance., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objectives: Patient-reported outcome measures allow children to directly report on their health and well-being. We assessed the construct validity and responsiveness of the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric measures in children and adolescents with ulcerative colitis (UC)., Methods: Through the Inflammatory Bowel Disease Partners Kids & Teens' Internet-based cohort, children with UC reported symptoms related to disease activity (Pediatric Ulcerative Colitis Activity Index), IMPACT-III health-related quality of life measure, and 5 PROMIS Pediatric measures (anxiety, depressive symptoms, pain interference, fatigue, and peer relationships). We included participants aged 9 to 17 years and conducted cross-sectional and longitudinal, mixed-linear regression analyses to examine the extent to which PROMIS Pediatric scores are associated with and respond to changes in Pediatric Ulcerative Colitis Activity Index and IMPACT-III., Results: We evaluated 91 participants with UC (mean age 13 years, 57% girls). Better PROMIS Pediatric scores were associated with lower disease activity, in both cross-sectional and longitudinal analyses. For a change from moderate/severe to remission, observed effect estimates were -5.1 points for anxiety, -5.0 for depressive symptoms, -14.7 for pain interference, -13.7 for fatigue, and 5.3 for peer relationships (P < 0.05 for all domains). Better PROMIS Pediatric scores were associated with improved IMPACT-III scores (P values <0.01), and changes in scores were moderately correlated with changes in IMPACT-III over time (adjusted P values <0.01)., Conclusions: This study provides evidence for the construct validity and longitudinal responsiveness of the PROMIS Pediatric measures in pediatric patients with UC, thus supporting their use in clinical research and patient care., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: We aimed to describe physician practice patterns in holding or continuing IBD therapy in the setting of COVID-19 infection, using the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease [SECURE-IBD] registry., Methods: IBD medications that were stopped due to COVID-19 were recorded in the SECURE-IBD registry in addition to demographic and clinical data. We conducted descriptive analyses to understand characteristics associated with stopping IBD medications in response to active COVID-19 infection., Results: Of 1499 patients, IBD medications were stopped in 518 [34.6%] patients. On bivariate and multivariable analyses, a diagnosis of ulcerative colitis or IBD-unspecified was associated with a lower odds of stopping medication compared with Crohn's disease (adjusted odds ratio [aOR] 0.6, 95% confidence interval [CI] 0.48, 0.75). When evaluating specific medications, 5-aminosalicylic acid was more likely to be continued [p <0.001] whereas anti-tumour necrosis factor therapy and immunomodulator therapy were more likely to be stopped [global p <0.001]. Other demographic and clinical characteristics did not affect prescription patterns., Conclusions: IBD medications other than immunomodulators were continued in the majority of IBD patients with COVID-19, in the international SECURE-IBD registry. Future studies are needed to understand the impact of stopping or continuing IBD medications on IBD- and COVID-19 related outcomes., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: We sought to evaluate COVID-19 clinical course in patients with IBD treated with different medication classes and combinations., Design: Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is a large, international registry created to monitor outcomes of IBD patients with confirmed COVID-19. We used multivariable regression with a generalised estimating equation accounting for country as a random effect to analyse the association of different medication classes with severe COVID-19, defined as intensive care unit admission, ventilator use and/or death., Results: 1439 cases from 47 countries were included (mean age 44.1 years, 51.4% men) of whom 112 patients (7.8%) had severe COVID-19. Compared with tumour necrosis factor (TNF) antagonist monotherapy, thiopurine monotherapy (adjusted OR (aOR) 4.08, 95% CI 1.73 to 9.61) and combination therapy with TNF antagonist and thiopurine (aOR 4.01, 95% CI 1.65 to 9.78) were associated with an increased risk of severe COVID-19. Any mesalamine/sulfasalazine compared with no mesalamine/sulfasalazine use was associated with an increased risk (aOR 1.70, 95% CI 1.26 to 2.29). This risk estimate increased when using TNF antagonist monotherapy as a reference group (aOR 3.52, 95% CI 1.93 to 6.45). Interleukin-12/23 and integrin antagonists were not associated with significantly different risk than TNF antagonist monotherapy (aOR 0.98, 95% CI 0.12 to 8.06 and aOR 2.42, 95% CI 0.59 to 9.96, respectively)., Conclusion: Combination therapy and thiopurines may be associated with an increased risk of severe COVID-19. No significant differences were observed when comparing classes of biologicals. These findings warrant confirmation in large population-based cohorts.MKH should be changed to MDK for co-last author line., Competing Interests: Competing interests: RCU has served as an advisory board member or consultant for Eli Lilly, Janssen, Pfizer and Takeda; research support from AbbVie, Boehringer Ingelheim and Pfizer. EB: no conflicts of interest. RG: speaker fees and Scientific Advisory Boards for AbbVie and Janssen. GGK: honoraria for speaking or consultancy from Abbvie, Janssen, Pfizer and Takeda. He has received research support from Ferring, Janssen, Abbvie, GlaxoSmith Kline, Merck and Shire. Ownership of a patent: treatment of inflammatory disorders, autoimmune disease, and PBC. UTI Limited Partnership, assignee. Patent WO2019046959A1. PCT/CA2018/051098. 7 September 2018. MK-H: speaker/consultant for AbbVie, Janssen and Takeda. JDL: personal fees from Johnson & Johnson Consumer Inc; grants, personal fees and other from Takeda Pharmaceuticals; personal fees and non-financial support from AbbVie; grants and personal fees from Janssen Pharmaceuticals; personal fees from Eli Lilly and Company; personal fees from Samsung Bioepis; personal fees from UCB; personal fees from Bristol-Myers Squibb; grants and personal fees from Nestle Health Science; personal fees from Bridge Biotherapeutics; personal fees from Celgene; personal fees from Merck; personal fees and other from Pfizer; personal fees from Gilead; personal fees from Arena Parmaceuticals; and personal fees from Protagonist Therapeutics. SCN: honoraria for speaking or consultancy from Abbvie, Janssen, Ferring, Tillotts and Takeda; research support from Ferring and AbbVie. WR has served as a speaker for Abbott Laboratories, Abbvie, Aesca, Aptalis, Astellas, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, PLS Education, Schering-Plough, Shire, Takeda, Therakos, Vifor and Yakult. He has been a consultant for Abbott Laboratories, Abbvie, Aesca, Algernon, Amgen, AM Pharma, AMT, AOP Orphan, Arena Pharmaceuticals, Astellas, Astra Zeneca, Avaxia, Roland Berger GmBH, Bioclinica, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Covance, Danone Austria, DSM, Elan, Eli Lilly, Ernest & Young, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Intrinsic Imaging, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, LivaNova, Mallinckrodt, Medahead, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nash Pharmaceuticals, Nestle, Nippon Kayaku, Novartis, Ocera, OMass, Otsuka, Parexel, PDL, Periconsulting, Pharmacosmos, Philip Morris Institute, Pfizer, Procter & Gamble, Prometheus, Protagonist, Provention, Robarts Clinical Trial, Sandoz, Schering-Plough, Second Genome, Seres Therapeutics, Setpointmedical, Sigmoid, Sublimity, Takeda, Therakos, Theravance, Tigenix, UCB, Vifor, Zealand, Zyngenia and 4SC. He has been as an advisory board member for Abbott Laboratories, Abbvie, Aesca, Amgen, AM Pharma, Astellas, Astra Zeneca, Avaxia, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Danone Austria, DSM, Elan, Ferring, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Sandoz, Schering-Plough, Second Genome, Setpointmedical, Takeda, Therakos, Tigenix, UCB, Zealand, Zyngenia and 4SC. He has received research funding from Abbott Laboratories, Abbvie, Aesca, Centocor, Falk Pharma GmbH, Immundiagnsotik and MSD. FR: consultation fee, research grant or honorarium from Janssen, Pfizer, Abbvie, Takeda, Celgene, Nestlé Health Science and Nestlé Nutrition Institute. FS: speaker and consultant for: AbbVie, Eurofarma, Ferring, Janssen, Pfizer, Sanofi, Takeda and UCB. FEU: no conflicts of interest. XZ: no conflicts of interest. J-FC: research grants from AbbVie, Janssen Pharmaceuticals and Takeda; receiving payment for lectures from AbbVie, Amgen, Allergan, Inc, Ferring Pharmaceuticals, Shire and Takeda; receiving consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, Celgene Corporation, Celltrion, Eli Lilly, Enterome, Ferring Pharmaceuticals, Genentech, Janssen Pharmaceuticals, Landos, Ipsen, Medimmune, Merck, Novartis, Pfizer, Shire, Takeda, Tigenix and Viela bio; and hold stock options in Intestinal Biotech Development and Genfit. MK has consulted for AbbVie, Janssen and Takeda, is a shareholder in Johnson & Johnson and has received research support from AbbVie and Janssen., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background & Aims: Chronic liver disease (CLD) and cirrhosis are associated with immune dysregulation, leading to concerns that affected patients may be at risk of adverse outcomes following SARS-CoV-2 infection. We aimed to determine the impact of COVID-19 on patients with pre-existing liver disease, which currently remains ill-defined., Methods: Between 25th March and 8th July 2020, data on 745 patients with CLD and SARS-CoV-2 (including 386 with and 359 without cirrhosis) were collected by 2 international registries and compared to data on non-CLD patients with SARS-CoV-2 from a UK hospital network., Results: Mortality was 32% in patients with cirrhosis compared to 8% in those without (p <0.001). Mortality in patients with cirrhosis increased according to Child-Pugh class (A [19%], B [35%], C [51%]) and the main cause of death was from respiratory failure (71%). After adjusting for baseline characteristics, factors associated with death in the total CLD cohort were age (odds ratio [OR] 1.02; 1.01-1.04), Child-Pugh A (OR 1.90; 1.03-3.52), B (OR 4.14; 2.4-7.65), or C (OR 9.32; 4.80-18.08) cirrhosis and alcohol-related liver disease (OR 1.79; 1.03-3.13). Compared to patients without CLD (n = 620), propensity-score-matched analysis revealed significant increases in mortality in those with Child-Pugh B (+20.0% [8.8%-31.3%]) and C (+38.1% [27.1%-49.2%]) cirrhosis. Acute hepatic decompensation occurred in 46% of patients with cirrhosis, of whom 21% had no respiratory symptoms. Half of those with hepatic decompensation had acute-on-chronic liver failure., Conclusions: In the largest such cohort to date, we demonstrate that baseline liver disease stage and alcohol-related liver disease are independent risk factors for death from COVID-19. These data have important implications for the risk stratification of patients with CLD across the globe during the COVID-19 pandemic., Lay Summary: This international registry study demonstrates that patients with cirrhosis are at increased risk of death from COVID-19. Mortality from COVID-19 was particularly high among patients with more advanced cirrhosis and those with alcohol-related liver disease., Competing Interests: Conflicts of interest The authors declare no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: PROMIS Pediatric domains provide self-reported measures of physical, emotional, and social health in children with chronic conditions. We evaluated the responsiveness of the PROMIS Pediatric measures to changes in disease activity and disease-specific, health-related quality of life (HRQOL) in children with Crohn's disease (CD)., Methods: IBD Partners Kids & Teens is an internet-based cohort of children with inflammatory bowel disease (IBD). Participants age 9 to 17 report symptoms related to disease activity (short Crohn's Disease Activity Index [sCDAI]), the IMPACT-III HRQOL measure, and 5 PROMIS Pediatric domains. We conducted longitudinal analyses using mixed linear models to examine the extent to which PROMIS Pediatric measures respond to changes in sCDAI and IMPACT-III., Results: Our study sample included 544 participants with CD (mean age 13 years, 44% female). All PROMIS Pediatric domains responded to changes in sCDAI, indicating improved physical, emotional, and social health, corresponding to improved disease activity and the converse (P < 0.001). Observed effect estimates ranged from 1.8 for peer relationships to 6.8 for fatigue. Of 246 participants with 2 or more completed reports, disease activity was stable in 527, worse in 72, and improved in 67. Changes in PROMIS Pediatric scores were associated with changes in IMPACT-III (r = -0.43 for anxiety, r = -0.45 for depressive symptoms, r = -0.43 for pain interference, r = -0.59 for fatigue, and r = 0.23 for peer relationships)., Conclusions: This study provides evidence for the longitudinal responsiveness of the PROMIS Pediatric measures to change in disease status and HRQOL in pediatric CD patients., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The coronavirus disease 2019 (COVID-19) pandemic caused by the highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents most often with mild clinical symptoms, but the severe forms are of major concern. 1 SARS-CoV-2 enters human cells via the angiotensin-converting enzyme 2 receptor, expressed on epithelial and endothelial cells. 2 Because the highest angiotensin-converting enzyme 2 expression is in the terminal ileum and colon, and up-regulated further during inflammation, and many COVID-19 patients experience gastrointestinal symptoms, longitudinal data are necessary to determine whether inflammatory bowel disease (IBD) patients are at risk for severe or complicated COVID-19. A recent analysis in IBD patients from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry showed older age, steroid medication, and comorbidities as risk factors for severe evolution, and the same study showed that the 29 IBD patients younger than age 20 had only mild disease courses. 3 This report describes the disease course of COVID-19 in an expanded sample of pediatric IBD patients from 2 international databases., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Despite concerns that patients with liver transplants might be at increased risk of adverse outcomes from COVID-19 because of coexisting comorbidities and use of immunosuppressants, the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on this patient group remains unclear. We aimed to assess the clinical outcomes in these patients., Methods: In this multicentre cohort study, we collected data on patients with laboratory-confirmed SARS-CoV-2 infection, who were older than 18 years, who had previously received a liver transplant, and for whom data had been submitted by clinicians to one of two international registries (COVID-Hep and SECURE-Cirrhosis) at the end of the patient's disease course. Patients without a known hospitalisation status or mortality outcome were excluded. For comparison, data from a contemporaneous cohort of consecutive patients with SARS-CoV-2 infection who had not received a liver transplant were collected from the electronic patient records of the Oxford University Hospitals National Health Service Foundation Trust. We compared the cohorts with regard to several outcomes (including death, hospitalisation, intensive care unit [ICU] admission, requirement for intensive care, and need for invasive ventilation). A propensity score-matched analysis was done to test for an association between liver transplant and death., Findings: Between March 25 and June 26, 2020, data were collected for 151 adult liver transplant recipients from 18 countries (median age 60 years [IQR 47-66], 102 [68%] men, 49 [32%] women) and 627 patients who had not undergone liver transplantation (median age 73 years [44-84], 329 [52%] men, 298 [48%] women). The groups did not differ with regard to the proportion of patients hospitalised (124 [82%] patients in the liver transplant cohort vs 474 [76%] in the comparison cohort, p=0·106), or who required intensive care (47 [31%] vs 185 [30%], p=0·837). However, ICU admission (43 [28%] vs 52 [8%], p<0·0001) and invasive ventilation (30 [20%] vs 32 [5%], p<0·0001) were more frequent in the liver transplant cohort. 28 (19%) patients in the liver transplant cohort died, compared with 167 (27%) in the comparison cohort (p=0·046). In the propensity score-matched analysis (adjusting for age, sex, creatinine concentration, obesity, hypertension, diabetes, and ethnicity), liver transplantation did not significantly increase the risk of death in patients with SARS-CoV-2 infection (absolute risk difference 1·4% [95% CI -7·7 to 10·4]). Multivariable logistic regression analysis showed that age (odds ratio 1·06 [95% CI 1·01 to 1·11] per 1 year increase), serum creatinine concentration (1·57 [1·05 to 2·36] per 1 mg/dL increase), and non-liver cancer (18·30 [1·96 to 170·75]) were associated with death among liver transplant recipients., Interpretation: Liver transplantation was not independently associated with death, whereas increased age and presence of comorbidities were. Factors other than transplantation should be preferentially considered in relation to physical distancing and provision of medical care for patients with liver transplants during the COVID-19 pandemic., Funding: European Association for the Study of the Liver, US National Institutes of Health, UK National Institute for Health Research., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: The impact of Coronavirus disease 2019 (COVID-19) on patients with inflammatory bowel disease (IBD) is unknown. We sought to characterize the clinical course of COVID-19 among patients with IBD and evaluate the association among demographics, clinical characteristics, and immunosuppressant treatments on COVID-19 outcomes., Methods: Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is a large, international registry created to monitor outcomes of patients with IBD with confirmed COVID-19. We calculated age-standardized mortality ratios and used multivariable logistic regression to identify factors associated with severe COVID-19, defined as intensive care unit admission, ventilator use, and/or death., Results: 525 cases from 33 countries were reported (median age 43 years, 53% men). Thirty-seven patients (7%) had severe COVID-19, 161 (31%) were hospitalized, and 16 patients died (3% case fatality rate). Standardized mortality ratios for patients with IBD were 1.8 (95% confidence interval [CI], 0.9-2.6), 1.5 (95% CI, 0.7-2.2), and 1.7 (95% CI, 0.9-2.5) relative to data from China, Italy, and the United States, respectively. Risk factors for severe COVID-19 among patients with IBD included increasing age (adjusted odds ratio [aOR], 1.04; 95% CI, 1.01-1.02), ≥2 comorbidities (aOR, 2.9; 95% CI, 1.1-7.8), systemic corticosteroids (aOR, 6.9; 95% CI, 2.3-20.5), and sulfasalazine or 5-aminosalicylate use (aOR, 3.1; 95% CI, 1.3-7.7). Tumor necrosis factor antagonist treatment was not associated with severe COVID-19 (aOR, 0.9; 95% CI, 0.4-2.2)., Conclusions: Increasing age, comorbidities, and corticosteroids are associated with severe COVID-19 among patients with IBD, although a causal relationship cannot be definitively established. Notably, tumor necrosis factor antagonists do not appear to be associated with severe COVID-19., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Dermatologic manifestations in patients with inflammatory bowel disease (IBD) are increasingly recognized as related disorders, secondary to specific therapies used to treat IBD, or complications of IBD itself. These dermatologic manifestations can be difficult to manage., Recent Findings: We summarize three categories of dermatologic manifestations in this review: extraintestinal cutaneous disorders, paradoxical manifestations to biologic therapies, and other drug-induced cutaneous manifestations. In particular, we provide current data surrounding clinical characteristics, epidemiology, and treatment modalities for individual cutaneous manifestations., Summary: Many extraintestinal cutaneous manifestations can be managed by optimized treatment of IBD itself, as shared treatment pathways exist. Paradoxical reactions to biologic agents may be driven by the individual biologic therapy. In these instances, if topical therapies or immunomodulators are not effective in treating the paradoxical cutaneous reaction, a change of class may be required. Nonmelanoma and melanoma skin cancers have been linked to specific therapies for IBD (including thiopurines and antitumor necrosis factor alpha agents, respectively). Therefore, optimizing preventive efforts towards skin cancer is warranted. Recognition of these cutaneous disorders by the practicing gastroenterologist is important, as is collaboration with dermatology for management of many cutaneous disorders.