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Background and Aims Integrated IBD care is effective but not routinely implemented. Validated methods that simultaneously address mind and body targets such as resilience may improve access and outcomes. We describe the development and implementation of the GRITTTM Method and its impact on resilience, health care resource utilization (HCRU) and opioid use in IBD. Methods Consecutive patients from an academic IBD center were evaluated for low resilience based on provider referral. Low resilience patients were invited to participate in the GRITTTM program. Primary outcome was % reduction in HCU. Secondary outcomes were change in resilience, corticosteroid and opioid use. Patients were allocated into 2 groups for analysis: GRITT Participants (GP) and Non-Participants (NP). Clinical data and HCU in the year prior to enrollment were collected at baseline and 12 months. One-way repeated measures MANCOVA evaluated group X time interactions for the primary outcome. Effect size was calculated for changes in resilience over time. Results Of 456 screened IBD patients 394 were eligible; 184 GP and 210 NP. GP had greater reduction in HCU than NP: 71% reduction in ED visits; 94% reduction in unplanned hospitalizations. There was a 49% reduction in opioid use and 73% reduction in corticosteroid use in GP. Resilience increased by 27.3 points (59%), yielding a large effect size (d=2.4). Conclusion Mind-body care that focuses on building resilience in the context of IBD care may be a novel approach to reduce unplanned health care utilization and opioid use but large, multi-center, randomized, controlled trials are needed.

Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Using a novel electronic reporting tool, we aimed to prospectively describe the onset of tofacitinib efficacy during induction therapy in a real-world study. Methods Patient-reported outcome data (PROs) including the simple clinical colitis activity index (SCCAI), PRO Measurement Identification Systems (PROMIS) measures, and adverse events were collected daily for the first 14 days and at day 28 and 56. Paired t tests and P for trend were utilized to compare changes in SCCAI over time. Bivariate analyses and logistic regression models were performed to describe response (SCCAI Results Of all included patients (n = 96), 67% had failed ≥2 biologics, and 61.5% were on concomitant steroids. Starting at day 3, PROs showed significant and persistent decline of the mean SCCAI (−1.1, P < 000.1) including significantly lower SCCAI subscores for stool frequency (−0.3; P < .003), bleeding (−0.3; P < .0002) and urgency (−0.2; P < .001). Steroid-free remission at day 14, 28, and 56 was achieved in 25%, 30.2%, and 29.2% of patients, respectively. Neither prior biologics nor endoscopic severity were independently predictive of response or remission in multivariate models. Numeric improvements in all PROMIS measures (anxiety, depression, social satisfaction) were seen through day 56. Rates of discontinuation due to adverse events were low. Conclusions In this prospective real-world study, tofacitinib resulted in a rapid and persistent improvement in UC disease activity PROs. The safety findings were consistent with the established safety profile of tofacitinib.

Background Patients with inflammatory bowel disease (IBD) are at an increased risk of malnutrition. The goal of this study was to define the prevalence of malnutrition and micronutrient deficiencies in recently diagnosed IBD patients and to compare the performance of existing malnutrition screening tools in identifying IBD patients at increased risk for malnutrition. Methods This was a retrospective cohort study of adult patients with recently diagnosed IBD (≤18 months disease duration). A diagnosis of malnutrition was made utilizing the European Society for Clinical Nutrition and Metabolism malnutrition criteria. Serum micronutrient levels were included. The sensitivity of 5 malnutrition screening tools in identifying patients at moderate-high risk of malnutrition was determined based on the European Society for Clinical Nutrition and Metabolism malnutrition definition. Descriptive statistics summarized the data and univariate analyses tested associations. Results A total of 182 patients were included for analysis; 65 (36%) met criteria for malnutrition. A total of 135 (74%) patients had ≥1 micronutrient level checked and 105 (78%) had ≥1 deficiency. Patients with prior surgery (odds ratio [OR], 4.5; P = .004), active Crohn’s disease (OR, 2.8; P = .03), and diarrhea (OR, 2.1; P = .02) were more likely to be malnourished. The Malnutrition Universal Screening Tool and Saskatchewan IBD Nutrition Risk Tool had the highest sensitivity (100%) in predicting those at moderate-high risk of malnutrition at the time of screening. Conclusions Patients with recently diagnosed IBD have a high prevalence of malnutrition and micronutrient deficiencies. Both the Malnutrition Universal Screening Tool and Saskatchewan IBD Nutrition Risk Tool can be used to identify those at increased risk of malnutrition. Future studies and screening tool development are necessary to identify those at risk of developing malnutrition to facilitate timely referral for nutritional evaluation and prevent disease related complications.

Background and Aims The impact of the COVID-19 pandemic on patients with inflammatory bowel disease [IBD] is largely unknown. We characterised the impact of COVID-19 on IBD care by conducting an analysis of US health care claims data. Methods We obtained de-identified, open-source, health insurance claims data, from January 2019 to December 2020, from the Symphony Health Integrated Dataverse for US adults with IBD, and measured the rates per 1000 patients of five outcomes: colonoscopies; new biologic or small molecule treatment initiations or treatment switches; new biologic or small molecule treatment initiations or treatment switches in patients who had a colonoscopy within the previous 60 days; IBD-related surgeries; and telehealth consultations. Results For 2019 and 2020, 1.32 million and 1.29 million patients with IBD, respectively, were included in the analysis. In March–April 2020, the rates of colonoscopies [17.39 vs 34.44], new biologic or small molecule treatment initiations or switches in patients who had a colonoscopy within the previous 60 days [0.76 vs 1.18], and IBD-related surgeries [2.33 vs 2.99] per 1000 patients were significantly decreased versus January–February 2020; significant year on year decreases versus 2019 were also observed. Telehealth utilisation increased in March 2020 and remained higher than in 2019 up to December 2020. Conclusions Reduction in colonoscopies and subsequent initiation/switching of treatments during the COVID-19 pandemic suggest lost opportunities for therapy optimisation which may have an impact on longer-term patient outcomes. Increased utilisation of telehealth services may have helped address gaps in routine clinical care.

BACKGROUND: Disability in patients with medically refractory ulcerative colitis (UC) after total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is not well understood. The aim of this study was to compare disability in patients with IPAA vs medically managed UC, and identify predictors of disability. METHODS: This was a multi-center cross-sectional study performed at five academic institutions in New York City. Patients with medically or surgically treated UC were recruited. Clinical and socioeconomic data were collected and the inflammatory bowel disease disability index (IBD-DI) was administered to eligible patients. Predictors of moderate-severe disability (IBD-DI≥35) were assessed in univariable and multivariable models. RESULTS: A total of 94 patients with IPAA and 128 patients with medically managed UC completed the IBD-DI. Among patients with IPAA and UC, 35 (37.2%) and 30 (23.4%) had moderate-severe disability, respectively. Patients with IPAA had significantly greater IBD-DI scores compared to patients with medically managed UC (29.8 vs 17.9, p

BACKGROUND: Escalation to anti-tumour necrosis factor (anti-TNF) in inflammatory bowel disease (IBD) patients on thiopurine is a common clinical scenario. However, the impact of discontinuing thiopurine at escalation is unclear.AIM: To assess the impact of discontinuing versus continuing thiopurine therapy at anti-TNF initiation.METHODS: We used the Danish registries to establish a national cohort of patients with IBD on thiopurine therapy prior to initiating anti-TNF from 2003 to 2018. We compared patients discontinuing thiopurine therapy within 90 days of anti-TNF initiation to those continuing. Our primary outcome was a composite of any new oral corticosteroid use, IBD-related hospitalization, surgery or death. We used Cox regression models to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI).RESULTS: Of the 10,352 anti-TNF exposed patients, 2,630 (1590 Crohn's disease (CD) and 1040 ulcerative colitis (UC)) received thiopurines prior to anti-TNF. After anti-TNF initiation, 979 patients discontinued thiopurines. Discontinuing thiopurines within 90 days of anti-TNF initiation, increased the risk of the primary outcome (aHR: 1.22; 95% CI: 1.10-1.36), particularly for IBD-related hospitalization (aHR: 1.14; 95% CI: 1.00-1.31) and oral corticosteroid use (aHR: 1.27; 95% CI: 1.13-1.44). This increased risk of the primary outcome was seen in both CD (aHR: 1.17; 95% CI 1.02-1.34) and UC (aHR: 1.32; 95% CI: 1.12-1.55).CONCLUSIONS: In a nationwide cohort study of IBD patients, we observed that discontinuing thiopurines after anti-TNF initiation was associated with an increased risk of adverse outcomes, in particular an increase in hospitalizations. Further interventional studies exploring this common clinical scenario are required.

Background & Aims We aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice. Methods A multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist–naive and –exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately. Results A total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist–naive and −exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between vedolizumab-treated and TNF-antagonist−treated patients. However, in TNF-antagonist−naive patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754). Conclusions Treatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist−naive patients.

Background Severe acute respiratory syndrome coronavirus 2 vaccination is recommended for all individuals with inflammatory bowel disease (IBD), including those on immunosuppressive therapies; however, little is known about vaccine safety and efficacy in these patients or the impact of vaccination on IBD disease course. Methods We evaluated coronavirus disease 2019 (COVID-19) vaccine–related adverse events (AEs) and the effect of vaccination on IBD disease course among participants in the PREVENT-COVID (Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID) study, a prospective, observational cohort study. Localized and systemic reactions were assessed via questionnaire. Disease flare was defined by worsening IBD symptoms and change in IBD medications. Outcomes were stratified by vaccine type and IBD medication classes. Results A total of 3316 individuals with IBD received at least 1 COVID-19 vaccine. Injection site tenderness (68%) and fatigue (46% dose 1, 68% dose 2) were the most commonly reported localized and systemic AEs after vaccination. Severe localized and systemic vaccine-related AEs were rare. The mRNA-1273 vaccine was associated with significantly greater severe AEs at dose 2 (localized 4% vs 2%, systemic 15% vs 10%; P < .001 for both). Prior COVID-19 infection, female sex, and vaccine type were associated with severe systemic reactions to dose 1, while age Conclusions Our findings provide reassurance that the severe acute respiratory syndrome coronavirus 2 vaccine is safe and well tolerated among individuals with IBD, which may help to combat vaccine hesitancy and increase vaccine confidence.

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.

Patients with inflammatory bowel disease (IBD) may take medications that affect their immune system, altering their ability to fight infection or making them less responsive to vaccines. Many of these patients were excluded from original studies regarding COVID-19, which creates a challenge for gastroenterologists to use evidence-based medicine to guide their management. We reviewed the available literature regarding patients with IBD and COVID-19 outcomes and response to vaccinations. Of all IBD patients, 0.3-24% acquired COVID-19 infection and 7-67% of those patients required hospitalization. Many studies have analyzed the effects of COVID-19 on patients with IBD. Observational studies suggest most IBD patients are not at higher risk from COVID-19 infection and that the COVID-19 vaccines are safe, effective and recommended. However, patients being treated with a TNF-α inhibitor with an immunomodulator and patients being treated with steroids should be monitored closely and efforts should be made to wean patients off of systemic steroids if possible. Patients treated with these regimens had lower antibody responses to vaccination and were at higher risk of acquiring severe COVID-19 infection. Antibody responses were robust after the second dose of mRNA vaccines with 85-100% of individuals showing seroconversion, albeit with lower levels of antibodies compared to the general population.

Background Anxiety and depression are comorbid disorders with IBD and are associated with poor outcomes. Resilience is an innate but modifiable trait that may improve the symptoms of psychological disorders. Increasing resilience may decrease the severity of these comorbid disorders, which may improve IBD outcomes. The aim of this study was to describe the association between resilience, anxiety, and depression in IBD patients. Methods We performed a cross-sectional study of IBD patients. Patients completed a questionnaire consisting of the Connor-Davidson Resilience Scale (CD-RISC), a measure of resilience, the Generalized Anxiety Disorder 7 (GAD-7), and the Patient Health Questionnaire-9. Primary outcome was severity of anxiety and depression in patients with high resilience. Multivariable linear regression analysis evaluated the association between severity of anxiety and depression and level of resilience. Results A sample of 288 patients was analyzed. Bivariable linear regression analysis showed a negative association between resilience and anxiety (Pearson rho = −0.47; P < .0001) and between resilience and depression (Pearson rho = −0.53; P < .0001). Multivariable linear regression indicated that high resilience is independently associated with lower anxiety and that for every 1-unit increase in CD-RISC, the GAD-7 score decreased by 0.04 units (P = .0003). Unlike anxiety, the association between resilience and depression did not remain statistically significant on multivariable analysis. Conclusions High resilience is independently associated with lower anxiety in IBD patients, and we report a quantifiable decrease in anxiety score severity for every point of increase in resilience score. These findings suggest that IBD patients with higher resilience may have better coping mechanisms that buffer against the development of anxiety.

Inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis, are chronic, progressive, immune-mediated diseases of adults and children that have no cure. IBD can cause significant morbidity and lead to complications such as strictures, fistulas, infections, and cancer. In children, IBD can also result in growth impairment and pubertal delays. IBD is highly heterogenous, with severity ranging from mild to severe and symptoms ranging from mild to debilitating. Delay in IBD diagnosis, especially in Crohn’s disease, is common and associated with adverse outcomes. Early diagnosis and prompt institution of treatment are the cornerstones for improving outcomes and maximizing health. Early diagnosis requires a low threshold of suspicion and red flags to guide early specialist referral at the primary provider level. Although the armamentarium of IBD medications is growing, many patients will not respond to treatment, and the selection of first-line therapy is critical. Risk stratification of disease severity, based on clinical, demographic, and serologic markers, can help guide selection of first-line therapy. Clinical decision support tools, genomics, and other biomarkers of response to therapy and risk of adverse events are the future of personalized medicine. After starting appropriate therapy, it is important to confirm remission using objective end points (treat to target) with continued control of inflammation with adjustment of therapy using surrogate biomarkers (tight control). Lastly, IBD therapy extends far beyond medications, and other aspects of the overall health and wellbeing of the patient are critical. These include preventive health, nutrition, and psychobehavioral support addressing patients’ concerns around complementary therapy and medication adherence, prevention of disability, and ensuring open communication.

On March 11, 2020 the World Health Organization declared the 2019 novel coronavirus (severe acute respiratory syndrome coronavirus-2 [SARS-CoV-2]) epidemic a global pandemic. Physicians, scientists, and patients scrambled to gain an understanding of the implications of this dire situation, and societies and organizations tried to provide guidance of best practices and precautions. In the inflammatory bowel disease community (IBD), the International Organization for the study of IBD (IOIBD) convened their expert members and performed a RAND panel assessment to develop recommendations for patients and providers. Others developed an international open registry to collect data about patients with IBD who developed Coronavirus Disease (COVID-19), the Surveillance Epidemiology of COVID-19 Under Research Exclusion (SECURE-IBD), in order to collect evidence on how COVID-19 impacted IBD patients. To date, SECURE-IBD has amassed 3,493 cases with outcomes3 and published initial analyses. In addition, there were multiple articles published with individual or multi-center experiences, city or regional experiences, and many case reports about IBD or immunemediated disease outcomes. Separately, there was significant activity by translational and basic scientists working to define and describe the pathophysiology of SARS-CoV-2 infections.

OBJECTIVE: There are limited data on the impact of coronavirus disease 2019 (COVID-19) on hospitalized patients with autoimmune and chronic inflammatory disease (AICID) compared with patients who do not have AICID. We sought to evaluate whether patients with AICID who have confirmed COVID-19 presenting to the hospital are at higher risk of adverse outcomes compared with those patients without AICID who are infected with COVID-19 and whether immunosuppressive medications impact this risk. METHODS: We performed a multicenter retrospective cohort study with patients presenting to five hospitals in a large academic health system with polymerase chain reaction-confirmed COVID-19 infection. We evaluated the impact of having an AICID and class of immunosuppressive medication being used to treat patients with AICID (biologics, nonbiologic immunosuppressives, or systemic corticosteroids) on the risk of developing severe COVID-19 defined as requiring mechanical ventilation (MV) and/or death. RESULTS: A total of 6792 patients with confirmed COVID-19 were included in the study, with 159 (2.3%) having at least one AICID. On multivariable analysis, AICIDs were not significantly associated with severe COVID-19 (adjusted odds ratio [aOR] 1.3, 95% confidence interval [CI]: 0.9-1.8). Among patients with AICID, use of biologics or nonbiologic immunosuppressives did not increase the risk of severe COVID-19. In contrast, systemic corticosteroid use was significantly associated with an increased risk of severe COVID-19 (aOR 6.8, 95% CI: 2.5-18.4). CONCLUSION: Patients with AICID are not at increased risk of severe COVID-19 with the exception of those on corticosteroids. These data suggest that patients with AICID should continue on biologic and nonbiologic immunosuppression but limit steroids during the COVID-19 pandemic.

Background While immunosuppression poses a theoretical increase in the risk of COVID‐19, the nature of this relationship is yet to be ascertained. Aims To determine whether immunosuppressed patients are at higher risk of COVID‐19 to help inform the management of patients receiving immunosuppressant therapies during the pandemic. Methods We performed a random‐effects meta‐analysis of data from studies that reported on the prevalence of immunosuppression among patient cohorts with COVID‐19. Results Sixty full‐text publications were identified. In total, six individual studies were included in the final analysis, contributing a total of 10 049 patients with COVID‐19 disease. The prevalence of immunosuppressed patients among the study cohorts with COVID‐19 ranged from 0.126% to 1.357%. In the pooled cohort a total of 64/10 049 (0.637%) patients with COVID‐19 disease was immunosuppressed. Observed to expected ratios were used to compare the prevalence of immunosuppression in cohorts with confirmed COVID‐19 disease to the background prevalence of immunosuppression in the general community. The observed to expected ratio of immunosuppression among patients with COVID‐19 illness, relative to the general community, was 0.12 (95% confidence interval: 0.05–0.27). Conclusions Compared to the general population, immunosuppressed patients were not at significantly increased risk of COVID‐19 infection. This finding provides support for current expert consensus statements, which have recommended the continuation of immunosuppressant therapy in the absence of COVID‐19.

Background Inflammatory bowel disease (IBD) is a complex disease with variable presentation, progression, and response to therapies. Current disease classification is based on subjective clinical phenotypes. The peripheral blood immunophenome can reflect local inflammation, and thus we measured 39 circulating immune cell types in a large cohort of IBD and control subjects and performed immunotype:phenotype associations. Methods We performed fluorescence-activated cell sorting or CyTOF analysis on blood from 728 Crohn’s disease, 464 ulcerative colitis, and 334 non-IBD patients, with available demographics, endoscopic and clinical examinations and medication use. Results We observed few immune cell types commonly affected in IBD (lowered natural killer cells, B cells, and CD45RA– CD8 T cells). Generally, the immunophenome was distinct between ulcerative colitis and Crohn’s disease. Within disease subtype, there were further distinctions, with specific immune cell types associating with disease duration, behavior, and location. Thiopurine monotherapy altered abundance of many cell types, often in the same direction as disease association, while anti-tumor necrosis factor (anti-TNF) monotherapy demonstrated an opposing pattern. Concomitant use of an anti-TNF and thiopurine was not synergistic, but rather was additive. For example, thiopurine monotherapy use alone or in combination with anti-TNF was associated with a dramatic reduction in major subclasses of B cells. Conclusions We present a peripheral map of immune cell changes in IBD related to disease entity and therapies as a resource for hypothesis generation. We propose the changes in B cell subsets could affect antibody formation and potentially explain the mechanism behind the superiority of combination therapy through the impact of thiopurines on pharmacokinetics of anti-TNFs., Graphical abstract

Vaccines against SARS-CoV-2 are important for protection from COVID-19; however, patients with immune-mediated conditions and patients taking immunosuppressive medications, including patients with inflammatory bowel disease (IBD), were excluded from studies demonstrating the safety and efficacy of these vaccines. This article provides an overview of the research and recommendations currently published on vaccines against COVID-19 in adult populations with IBD, including studies evaluating effects of commonly used medications. COVID-19 vaccines are strongly recommended for patients with IBD. Messenger RNA (mRNA) and adenovirus vector vaccines are safe in patients with IBD, and reports of severe reactions or IBD flares are rare. Studies assessing antibody response, T-cell immunity, and real-world experience demonstrate positive outcomes for mRNA and adenovirus vector vaccines in patients with IBD, although mRNA vaccines may have a slight advantage. Studies assessing inactive COVID-19 vaccines are still needed. Immunosuppressive therapies used in IBD, especially tumor necrosis factor antagonists, combination therapy, and corticosteroids, may reduce antibody responses and durability, but the impact on infection, hospitalizations, and death requires further evaluation. Educating patients with this evidence-based information will likely help to reduce concerns and vaccine hesitancy.

Patients with inflammatory bowel diseases [IBD] are frequently treated with immunosuppressant medications. During the coronavirus disease 2019 [COVID-19] pandemic, recommendations for IBD management have included that patients should stay on their immunosuppressant medications if they are not infected with the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], but to temporarily hold these medications if symptomatic with COVID-19 or asymptomatic but have tested positive for SARS-CoV-2. As more IBD patients are infected globally, it is important to also understand how to manage IBD medications during convalescence while an individual with IBD is recovering from COVID-19. In this review, we address the differences between a test-based versus a symptoms-based strategy as related to COVID-19, and offer recommendations on when it is appropriate to consider restarting IBD therapy in patients testing positive for SARS-CoV-2 or with clinical symptoms consistent with COVID-19. In general, we recommend a symptoms-based approach, due to the current lack of confidence in the accuracy of available testing and the clinical significance of prolonged detection of virus via molecular testing.

Summary Intake of specific dietary macro- and micronutrients has been implicated in modulating the risk of inflammatory bowel disease (IBD)(Nat Rev Gastroenterol Hepatol 2018;15:525-535). Recent epidemiological and pre-clinical studies have additionally examined the impact of non-nutritional dietary components on IBD. Ultra-processed foods (UPF), as defined by the NOVA classification, are foods of mainly industrial origin, often containing little or no whole foods but many ingredients including food additives such as artificial colors and flavors, stabilizers, emulsifiers, and preservatives(Public Health Nutr 2019;22:936-941). The objective of the study by Narula et al (BMJ 2021;374:n1554) was to examine the association between intake of UPF and the risk of developing IBD.

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.

Approximately 20% of patients with ulcerative colitis (UC) who undergo total proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA) develop chronic pouch inflammation (CPI).

Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). We present an updated analysis of adjudicated malignancies in the tofacitinib UC clinical programme, including final data from the open-label, long-term extension (OLE) study (as of 24 Aug 2020). Methods Malignancies were evaluated from 3 randomised, placebo-controlled studies (2 Phase [P]3 induction studies [NCT01465763; NCT01458951]; 1 P3 maintenance study [NCT01458574]) and an OLE study (NCT01470612). Three cohorts were analysed: Induction (P3 induction studies), Maintenance (P3 maintenance study) and Overall (patients receiving tofacitinib 5 or 10 mg twice daily [BID] in P3 or OLE studies; data from the previous data cut [May 2019] are also reported for comparison). Analysis was by predominant dose (PD) 5 or 10 mg BID, based on average daily dose Results 1124 patients were evaluated for malignancies (2809.4 patient-years of tofacitinib exposure; up to 7.8 years of treatment; median duration of 685.5 days). No malignancies (excluding NMSC) occurred in Induction Cohort patients. Malignancies (excluding NMSC) occurred in 1 Maintenance Cohort patient (who was receiving placebo) and in 25 Overall Cohort patients (IR 0.86 [95% confidence interval (CI) 0.56, 1.27]: PD tofacitinib 5 mg BID n=5, IR 0.63 [95% CI 0.20, 1.47]; PD tofacitinib 10 mg BID n=20, IR 0.95 [95% CI 0.58, 1.46]); 5 new cases since May 2019 (Table).1 NMSC events in the Induction and Maintenance Cohorts were previously reported (Table).1 NMSC events occurred in 21 Overall Cohort patients (IR 0.73 [95% CI 0.45, 1.12]): PD tofacitinib 5 mg BID n=5, IR 0.63 (95% CI 0.21, 1.48); PD tofacitinib 10 mg BID n=16, IR 0.77 (95% CI 0.44, 1.25); 2 new cases since May 2019 (Table).1 Conclusion There was no apparent clustering of types of malignancy, excluding NMSC. Malignancies (excluding NMSC) and NMSC IRs remained stable over time, being comparable to those previously reported in the tofacitinib UC clinical programme.1 In this analysis, malignancies (excluding NMSC) and NMSC IRs were similar to those in patients with UC treated with tumour necrosis factor inhibitors, as reported from claims data (IRs of 0.63 and 1.69, respectively).2 References

Biologic therapies have greatly advanced the medical care of patients with Crohn's disease (CD); however, up to 50% of patients have no response and up to 80% fail to achieve remission.

ObjectivesDevelop an individualised prognostic risk prediction tool for predicting the probability of adverse COVID-19 outcomes in patients with inflammatory bowel disease (IBD).Design and settingThis 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).ParticipantsWe 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 measuresCOVID-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.ResultsOf 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.ConclusionsPrognostic 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.

Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). These post hoc analyses assessed associations between C-reactive protein (CRP), partial Mayo score (PMS), and efficacy outcomes during tofacitinib induction in UC. Methods Patients received tofacitinib 10 mg twice daily (BID) in an 8-week, phase 2 induction study and 2 identical, 8-week, phase 3 induction studies (OCTAVE Induction 1&2); induction nonresponders (IndNR) received an additional 8 weeks of tofacitinib 10 mg BID in an open-label, long-term extension study. Associations between CRP and PMS, and efficacy outcomes (clinical response, clinical remission, endoscopic improvement, and endoscopic remission) were analyzed using univariate and multivariable logistic regression and receiver operating characteristic curves. Results Changes from baseline in the logarithm of CRP ([log]CRP) and PMS at week 4 were associated with clinical response at week 8 (univariate: per unit, odds ratio [OR], 0.55 [95% confidence interval (CI), 0.48-0.62]; and 0.42 [0.37-0.47], respectively). Among IndNR, change from baseline in PMS at week 8 was associated with clinical response at week 16 (univariate: per unit, OR, 0.59; 95% CI, 0.46-0.75). C-reactive protein at week 4 (area under the curve [AUC] > 0.6) and PMS at weeks 2 and 4 (AUC, > 0.7) generally exhibited predictive value for week 8 efficacy outcomes. Conclusions Patients who achieved clinical response at week 8 had larger decreases in CRP and PMS at week 4 than patients who did not. IndNR who achieved clinical response at week 16 with extended tofacitinib induction had a larger decrease in PMS at week 8 vs those who did not. ClinicalTrials.gov:NCT00787202;NCT01465763;NCT01458951;NCT01470612.

Background and Aims The aim of this study was to examine the risk of new-onset inflammatory bowel disease [IBD] following bariatric surgery. Methods We conducted a nationwide population-based prospective cohort study of the entire Danish population 18 to 60 years of age, alive, and residing in Denmark, from 1996 to 2018. Bariatric surgery was included as a time-dependent variable, and Cox proportional hazards regression models were used to estimate hazard ratios [HRs] of IBD. We used a model adjusting for age, sex, and birth cohort and a multifactor-adjusted model additionally including educational status and number of obesity-related comorbidities. Results We followed 3 917 843 individuals of whom 15 347 had a bariatric surgery, for development of new-onset IBD. During 106 420 person-years following bariatric surgery, 100 IBD events occurred [incidence rate 0.940/1000 person-years]. During 55 553 785 person-years without bariatric surgery, 35 294 events of IBD occurred [incidence rate 0.635/1000 person-years]. This corresponded to a multifactor-adjusted hazard ratio [HR] of 1.15 (95% confidence interval[CI], 0.94–1.40) for IBD. Multifactor-adjusted HRs of Crohn’s disease [CD] and ulcerative colitis [UC] were 1.85 [95% CI, 1.40–2.44] and 0.81 [95% CI, 0.61–1.08], respectively. Among women, the multifactor-adjusted HR for CD was 2.18 [95% CI, 1.64–2.90]. When limiting the study population to individuals with a diagnosis of overweight/obesity, bariatric surgery remained associated with increased risk of CD, multifactor-adjusted HR 1.59 [95% CI, 1.18–2.13]. Conclusions This nationwide cohort study shows that bariatric surgery is associated with increased risk of development of new-onset CD, but not of UC. The underlying mechanisms remain elusive.

Patients with immune-mediated inflammatory diseases such as inflammatory bowel disease (IBD) on immunosuppressive and biologic therapies were largely excluded from severe acute respiratory syndrome coronavirus-2 messenger RNA vaccine trials.We evaluated adverse events (AE) after messenger RNA vaccination in 246 adults with IBD participating in a longitudinal vaccine registry.In general, AE frequency was similar to that reported in the general population. AEs were more common among younger patients and those with previous COVID-19. AEs were less common in individuals receiving advanced therapies with biologics or small-molecule inhibitors.Those with IBD and other immune-mediated inflammatory diseases can be reassured that the AE risk is likely not increased, and may be reduced, while on advanced therapies.

BACKGROUND: Colectomy risk after acute severe ulcerative colitis (ASUC) has not been compared between Eastern and Western countries. We compared the 1-year colectomy risk after ASUC between Korea and the USA. METHODS: Data on patients admitted for ASUC to five tertiary referral hospitals in Korea and Mount Sinai Hospital, New York, the USA, between January 2015 and January 2019 were reviewed retrospectively. For comparability between groups, a 1:1 propensity score matching (PSM) was performed. The primary outcome was colectomy, and secondary outcomes were mortality, readmission, and venous thromboembolism (VTE) within 1-year of the index admission for ASUC. The risk of each outcome was compared using Cox proportional hazards model in pre-matched cohort and Kaplan–Meier analysis with log-rank test in post-matched cohort. RESULTS: 290 ASUC patients were included in the study (121 Korea, 169 the USA). After PSM, 56 patients were selected in each group with no significant differences in baseline variables. At 1 year after ASUC, colectomy was less common in Korea than in the USA [3 (5.4%) vs. 24 (42.9%), p < 0.001]. The cumulative colectomy risk was significantly higher in the USA than in Korea in pre-matched cohort [adjusted hazard ratio 7.89, 95% confidence interval 3.23 to 19.22] and in post-matched cohort (log-rank p < 0.001), while there was no difference in cumulative risk of mortality, readmission, and VTE. CONCLUSION: Colectomy risk within 1 year of ASUC is significantly higher in the USA than in Korea. We observed no differences in mortality, readmission, and VTE between the two groups.

Despite improved therapeutic strategies and expanding therapeutic targets, inflammatory bowel disease remains a disabling disease with potential to progress and lead to irreversible complications. Increased evidence supports the concept of a preclinical phase in inflammatory bowel disease, preceding clinical diagnosis, during which immune and inflammatory pathways are already altered. As knowledge about this prediagnosis period expands, it unlocks the possibility of disease prediction and ambition for disease prevention and interception. Targeting the early pathogenic events that promote the development of inflammatory bowel disease could prevent or attenuate disease onset and offer a true opportunity for disease modification.

Background: Most data on the effect of inflammatory bowel disease (IBD) and its treatments on coronavirus disease 2019 (COVID-19) outcomes have not had non-IBD comparators. Hence, we aimed to describe COVID-19 outcomes in IBD compared to non-IBD patients. Methods: We conducted a prospective cohort study of registered IBD patients with confirmed COVID-19 from six provinces in Iran from February to April 2020. Proven COVID-19 patients were followed up at four weeks and the frequency of outcomes was assessed. Multivariable logistic regression was used to assess associations between demographics, clinical characteristics and COVID-19 outcomes. Results: Overall, 2159 IBD patients and 4721 household members were enrolled, with 84 (3.9%) and 49 (1.1%) participants having confirmed COVID-19, respectively. Household spread of COVID-19 was not common in this cohort (1.2%). While hospitalization was significantly more frequent in IBD patients compared with non-IBD household members (27.1% vs. 6.0%, P=0.002), there was no significant difference in the frequency of severe cases. Age and presence of IBD were positively associated with hospitalization in IBD compared with non-IBD household members (OR: 1.06, 95% CI: 1.03-1.10; OR: 5.7, 95% CI: 2.02– 16.07, respectively). Age, presence of new gastrointestinal symptoms, and 5-aminosalicylic acid (5-ASA) use were associated with higher hospitalization rate in IBD patients (OR: 1.13, 95% CI: 1.05–1.23; OR: 6.49, 95% CI: 1.87–22.54; OR: 6.22, 95% CI: 1.90–20.36, respectively). Anti-tumor necrosis factor (TNF) was not associated with more severe outcomes. Conclusion: Age, presence of new gastrointestinal symptoms and use of 5-ASA were associated with increased hospitalization rate among IBD patients, while anti-TNF therapy had no statistical association.

Background: Concerns have been raised that the risk of severe acute respiratory syndrome coronavirus 2 infection, or more severe or critical coronavirus disease 2019 (COVID-19), may be higher in immunocompromised individuals receiving immunomodulatory therapies compared with immunocompetent individuals. Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis. To date, data on tofacitinib treatment during the COVID-19 pandemic are limited. Objectives: To summarize current understanding of the use of tofacitinib in adults during the COVID-19 pandemic, and discuss research questions that are yet to be addressed, to further inform the safe and effective use of tofacitinib in clinical practice. Methods: We conducted a review of the literature (as of February 2021), to summarize the expert recommendations for the management of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis in the context of COVID-19, and to assess the current data regarding the use of tofacitinib in adult patients during the pandemic. Results: Current recommendations for rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis state that tofacitinib treatment should be continued during the pandemic, except in cases of positive or presumed severe acute respiratory syndrome coronavirus 2 infection. However, limited data are available; analyses of data from international rheumatology and gastroenterology registries have suggested that tofacitinib may not be associated with an increased risk of hospitalization or treatment switching in adults with COVID-19. Conclusions: Further assessment of tofacitinib use in patients with rheumatoid arthritis, psoriatic arthritis, or ulcerative colitis will be required to elucidate and establish the benefit:risk profile of tofacitinib during the current COVID-19 pandemic.

We have previously described a prognostic transcriptional signature in CD8 T cells that separates patients with IBD into two phenotypically distinct subgroups, termed IBD1 and IBD2. Here we sought to develop a blood-based test that could identify these subgroups without cell separation, and thus be suitable for clinical use in Crohn's disease (CD) and ulcerative colitis (UC).Patients with active IBD were recruited before treatment. Transcriptomic analyses were performed on purified CD8 T cells and/or whole blood. Phenotype data were collected prospectively. IBD1/IBD2 patient subgroups were identified by consensus clustering of CD8 T cell transcriptomes. In a training cohort, machine learning was used to identify groups of genes ('classifiers') whose differential expression in whole blood recreated the IBD1/IBD2 subgroups. Genes from the best classifiers were quantitative (q)PCR optimised, and further machine learning was used to identify the optimal qPCR classifier, which was locked down for further testing. Independent validation was sought in separate cohorts of patients with CD (n=66) and UC (n=57).In both validation cohorts, a 17-gene qPCR-based classifier stratified patients into two distinct subgroups. Irrespective of the underlying diagnosis, IBDhi patients (analogous to the poor prognosis IBD1 subgroup) experienced significantly more aggressive disease than IBDlo patients (analogous to IBD2), with earlier need for treatment escalation (hazard ratio=2.65 (CD), 3.12 (UC)) and more escalations over time (for multiple escalations within 18 months: sensitivity=72.7% (CD), 100% (UC); negative predictive value=90.9% (CD), 100% (UC)).This is the first validated prognostic biomarker that can predict prognosis in newly diagnosed patients with IBD and represents a step towards personalised therapy.