Post-Discharge Outcomes of Elderly Patients Hospitalized for Inflammatory Bowel Disease Flare Complicated by Clostridioides difficile Infection.

OBJECTIVES: Elderly hospitalized patients with inflammatory bowel disease (IBD) flare and concurrent Clostridioides difficile infection (CDI) are considered at high risk of IBD-related complications. We aimed to evaluate the short, intermediate, and long-term post-discharge complications among these patients. METHODS: A retrospective multicenter cohort study assessing outcomes of elderly individuals (≥60 years) hospitalized for an IBD flare who were tested for CDI (either positive or negative) and discharged. The primary outcome was the 3-months post-discharge IBD-related complication rates defined as: steroid dependency, re-admissions (emergency department or hospitalization), IBD-related surgery, or mortality. We assessed post-discharge IBD-related complications within 6-months and mortality at 12-months among secondary outcomes. Risk factors for complication were assessed by multivariable logistic regression. RESULTS: In a cohort of 654 patients hospitalized for IBD (age 68.9 [interquartile range {IQR}]:63.9-75.2) years, 60.9% ulcerative colitis), 23.4% were CDI-positive. Post-discharge complication rates at 3 and 6-months, and 12-months mortality, did not differ significantly between CDI-positive and CDI-negative patients (32% vs. 33.1%, p=0.8; 40.5% vs. 42.5%, p=0.66; and 4.6% vs. 8%, p=0.153, respectively). The Charlson comorbidity index was the only significant risk factor for complications within 3-months (aOR 1.1), whereas mesalamine (5-aminosalicylic acid [5-ASA]) use was protective (aOR 0.6). An ulcerative colitis diagnosis was the sole risk factor for complication at 6-months (aOR 1.5). CDI did not significantly impact outcomes or interact with IBD type. CONCLUSIONS: In elderly IBD patients hospitalized for IBD flare and subsequently discharged, a concurrent CDI infection was not associated with post-discharge IBD-related complications or mortality up to 1-year.

Low-Grade Activation of the Extrinsic Coagulation Pathway in Patients with Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) increases the risk for venous thromboembolism. Tissue factor (TF) initiates the extrinsic coagulation pathway (ECP). AIMS: To investigate the correlation of UC severity with latent ECP activation and TF expression in primary colonic stromal cells (PCSC). METHODS: In plasma of 38 UC patients (31 males, disease duration 151 ± 25 months) and 28 healthy controls, exosomes and microparticles (EM) were counted. Moreover, TF protein concentration, activities of EM-bound TF (EM-TFa) and coagulation factor VII (FVIIa) were assessed. In PCSC in culture, TF mRNA (F3) from 12 patients with active UC and 7 controls was evaluated. RESULTS: UC patients had 4- and 3.7- times more exosomes and microparticles, respectively, than controls. TF protein in UC was correlated with several disease severity indices, such as partial Mayo score (pMs; r 0.443), albumin (- 0.362), ESR (0.353), PLT (0.575), and endoscopic Ms (eMs 0.468). EM-TFa was also significantly higher in UC and was correlated to SIBDQ (- 0.64), albumin (- 0.624), disease extent and eMs (0.422). Refractory-to-treatment patients had significantly higher TF protein, EM-TFa and FVIIa. Even within responders, the need for steroids or biologics correlated with a 2.2-times higher EM-TFa. PCSC from active UC maintained higher F3 than controls, which was correlated to pMs (0.56), albumin (- 0.543) and eMs. Treatment with cytokines further upregulated F3. P for all comparisons was < 0.05. CONCLUSION: Low-grade activation of the ECP associates with clinical, endoscopic UC activity and response to treatment. TF in PCSC mirrors its systemic activity and points to them as a source.

Iron therapy supplementation in inflammatory bowel disease patients with iron deficiency anemia: findings from a real-world analysis in Italy.

BACKGROUND: This real-world analysis evaluated iron therapy supplementation in inflammatory bowel disease patients with iron-deficiency anemia, considering disease progression and healthcare resource consumption. METHODS: A retrospective observational study was conducted using administrative databases of a pool of Italian healthcare entities, covering about 9.3 million beneficiaries. Between January 2010 and September 2017, adult patients were enrolled in the presence of either hospitalization or active exemption code for ulcerative colitis/Crohn's disease, or one vedolizumab prescription. Iron-deficiency anemia was identified by at least one prescription for iron and/or hospitalization for iron-deficiency anemia and/or blood transfusion (proxy of diagnosis). Patients were divided in untreated and iron-treated during 12-month follow-up and analyzed before and after propensity score matching. Disease progression, was evaluated through inflammatory bowel disease-related hospitalizations and surgeries, and healthcare resource utilization was assessed. RESULTS: Overall, 1753 patients were included, 1077 (61.4%) treated with iron therapy and 676 (38.6%) untreated. After propensity score matching, 655 patients were included in each group. In unbalanced cohorts, disease progression was significantly reduced in patients receiving iron therapy compared to the untreated (11.0% vs. 15.7%, P  < 0.01), and this trend was maintained also after applying propensity score matching. The overall mean cost/patient was significantly lower in iron-treated than untreated (4643€ vs. 6391€, P  < 0.01). CONCLUSION: The findings of this real-world analysis suggest that iron therapy was associated with significant benefits in inflammatory bowel disease patients with iron-deficiency anemia, in terms of both disease progression and healthcare resource utilization.

Bariatric Nutritional Intervention in Obese Patients with Compensated Liver Cirrhosis: A Four-Year Prospective Study.

BACKGROUND: Obesity and liver cirrhosis represent significant health challenges, often leading to various complications. AIMS: This prospective study aimed to investigate the impact of a four-year bariatric intervention, focusing on adherence to the Mediterranean Diet, on anthropometric, hematologic, and biochemical parameters in obese patients with compensated liver cirrhosis. Additionally, the study evaluated the concurrent contribution of weight loss to these health indicators. METHODS: The study involved 62 patients with compensated liver cirrhosis (mean age 65.87 ± 6 years) and 44 healthy controls (mean age 59.11 ± 8 years), all with a BMI > 30 kg/m2. Both groups underwent a weight loss intervention based on the Mediterranean diet, with a four-year follow-up. Anthropometric, biochemical and hematologic parameters were evaluated at several time points during the study and their statistical significance was assessed. RESULTS: Anthropometric parameters, including weight, BMI, waist and hip circumference, percentage of fat mass, and handgrip strength, exhibited significant improvements (p < 0.05), particularly within the first year of the intervention. Liver function tests and lipid profiles of the patients also showed significant enhancements (p < 0.05). Hematological and biochemical indices, such as hematocrit and ferritin, experienced discreet improvements in the patient cohort (p < 0.05). CONCLUSIONS: This study highlights the potential of a structured bariatric intervention rooted in the Mediterranean diet to positively influence the health of obese patients with compensated liver cirrhosis. The observed improvements in anthropometric, biochemical, and hematologic parameters, particularly within the first year of the intervention, suggest the importance of dietary modifications in managing the health of this patient population.

Prophylactic Versus Endoscopy-driven Treatment of Crohn's Postoperative Recurrence: A Retrospective, Multicentric, European Study [PORCSE Study].

BACKGROUND AND AIMS: No consensus exists on optimal strategy to prevent postoperative recurrence [POR] after ileocaecal resection [ICR] for Crohn's disease [CD]. We compared early medical prophylaxis versus expectant management with treatment driven by findings at elective endoscopy 6-12 months after ICR. METHODS: A retrospective, multicentric, observational study was performed. CD patients undergoing first ICR were assigned to Cohort 1 if a biologic or immunomodulator was [re]started prophylactically after ICR, or to Cohort 2 if no postoperative prophylaxis was given and treatment was started as reaction to elective endoscopic findings. Primary endpoint was rate of endoscopic POR [Rutgeerts >i1]. Secondary endpoints were severe endoscopic POR [Rutgeerts i3/i4], clinical POR, surgical POR, and treatment burden during follow-up. RESULTS: Of 346 included patients, 47.4% received prophylactic postoperative treatment [proactive/Cohort 1] and 52.6% did not [reactive/Cohort 2]. Endoscopic POR [Rutgeerts >i1] rate was significantly higher in Cohort 2 [41.5% vs 53.8%, OR 1.81, p = 0.039] at endoscopy 6-12 months after surgery. No significant difference in severe endoscopic POR was found [OR 1.29, p = 0.517]. Cohort 2 had significantly higher clinical POR rates [17.7% vs 35.7%, OR 3.05, p = 0.002] and numerically higher surgical recurrence rates [6.7% vs 13.2%, OR 2.59, p = 0.051]. Cox proportional hazards regression analysis showed no significant difference in time to surgical POR of proactive versus expectant/reactive approach [HR 2.50, p = 0.057]. Quasi-Poisson regression revealed a significantly lower treatment burden for immunomodulator use in Cohort 2 [mean ratio 0.53, p = 0.002], but no difference in burden of biologics or combination treatment. CONCLUSIONS: The PORCSE study showed lower rates of endoscopic POR with early postoperative medical treatment compared with expectant management after first ileocaecal resection for Crohn's disease.

Analysis of Clinical Trial Screen Failures in Inflammatory Bowel Diseases (IBD): Real World Results from the International Organization for the study of IBD.

BACKGROUND: Recruitment for randomized controlled trials (RCTs) in IBD have substantially dropped over time. This study aimed to assess reasons why IBD patients are not included in sponsored multicenter phase IIb-III RCTs. METHODS: All IOIBD members (n=58) were invited to participate. We divided barriers to participation as follow: 1) reasons patients with active IBD were not deemed appropriate for a RCT; 2) reasons qualified patients did not wish to participate; 3) reasons for screen failure (SF) in patients agreeing to participate. We assess those in a 4-week prospective study including, consecutively, all patients with symptomatic disease for whom a treatment change was required. In addition, we performed a 6-month retrospective study to further evaluate reasons for SF. RESULTS: A total of 106 patients (60 male (56.6%), 63 Crohn's disease [CD] (59.4%)), from 10 centers across the world, were included in the prospective study. A RCT has not been proposed to 65 of them (mainly due to eligibility criteria). Of the 41 patients to whom a RCT was offered, 8 refused (mainly due to reluctance to receive placebo) and 28 agreed to participate. Among these 28 patients, 5 failed their screening and 23 were finally included in a RCT. A total of 107 patients (61 male (57%), 67 CD (62.6%)), from 13 centers worldwide, were included in our retrospective study of SFs. The main reason was insufficient disease activity. CONCLUSION: This first multicenter study analyzing reasons for non-enrollment in IBD RCTs shown that we lose patients at each step. Eligibility criteria, the risk of placebo assignment and insufficient disease activity were part of the main barriers.

Etiology of Anemia and Risk Factors of Mortality among Hospitalized Patients: A Real-Life Retrospective Study in a Tertiary Center in Greece.

Anemia is a prominent global health issue with a wide variety of causes and can be associated with decreased quality of life, increased hospitalization, and higher mortality, especially in older individuals. Therefore, studies further shedding light on the causes and the risk factors of this condition should be performed. The aim of the present study was to examine the causes of anemia in hospitalized patients in a tertiary hospital in Greece and identify risk factors related to higher mortality. In total, 846 adult patients with a diagnosis of anemia were admitted during the study period. The median age was 81 years, and 44.8% were male. The majority of patients had microcytic anemia, with the median mean corpuscular volume (MCV) being 76.3 fL and the median hemoglobin being 7.1 g/dL. Antiplatelets were used by 28.6% of patients, while 28.4% were using anticoagulants at the time of diagnosis. At least one unit of packed red blood cells (PRBCs) was transfused in 84.6% of patients, and a median of two PRBCs was used per patient. A gastroscopy was performed in 55%, and a colonoscopy was performed in 39.8% of patients in the present cohort. Anemia was considered to be multifactorial in almost half the cases, while the most commonly identified cause was iron deficiency anemia, more commonly with positive endoscopic findings. Mortality was relatively low, at 4.1%. Multivariate logistic regression analysis identified higher B12 levels and longer duration of hospital stay to be independently positively associated with mortality.

Iron deficiency anemia impacts disease progression and healthcare resource consumption in patients with inflammatory bowel disease: a real-world evidence study.

Background: Iron deficiency anemia (IDA) is a common extraintestinal manifestation of inflammatory bowel disease (IBD), affecting around one-third of patients. Objective: To compare IBD progression and healthcare resource utilization in patients with and without a co-diagnosis of IDA in a real-world setting. Design: A retrospective comparative study was conducted using Italian entities' administrative databases, covering 9.3 million health-assisted individuals. Methods: Adult IBD patients diagnosed with ulcerative colitis and/or Crohn's disease were enrolled between January 2010 and September 2017. Within 12 months from IBD diagnosis, IDA was identified by at least one prescription for iron and/or IDA hospitalization and/or blood transfusion (proxy of diagnosis). IBD population was divided according to the presence/absence of IDA. Given the nonrandom patients' allocation, propensity score matching (PSM) was applied to abate potential unbalances between the groups. Before and after PSM, IBD progression (in terms of IBD-related hospitalizations and surgeries), and healthcare resource costs were assessed. Results: Overall, 13,475 IBD patients were included, with an average age at diagnosis of 49.9 years, and a 53.9% percentage of male gender. Before PSM, 1753 (13%) patients were IBD-IDA, and 11,722 (87%) were IBD-non-IDA. Post-PSM, 1753 IBD-IDA patients were matched with 3506 IBD-non-IDA. Before PSM, IBD progression was significantly higher in IBD-IDA (12.8%) than in IBD-non-IDA (6.5%) (p < 0.001). After PSM, IBD progression and IBD-related hospitalizations were significantly (p < 0.001) more frequent in IBD-IDA patients (12.8% and 12.0%, respectively) compared to IBD-non-IDA (8.7% and 7.7%). Consistently, healthcare expenditures resulted significantly higher among IDA patients (p < 0.001), with an overall mean annual cost of €5317 compared to €2798 for patients without IDA. These results were confirmed after PSM matching, as the mean annual total cost/patient in IBD-IDA versus IBD-non-IDA were €3693 and €3046, respectively (p < 0.001). Conclusion: In a real-life setting, IDA co-diagnosis in IBD patients was associated with disease progression and higher related economic burden.

The Inflammatory Bowel Disease-Disk Tool for Assessing Disability in Inflammatory Bowel Disease Patients: Validation of the Greek Version.

BACKGROUND: The Inflammatory Bowel Disease-Disk (IBD-Disk) is a physician-administered tool that evaluates the functional status of patients with Inflammatory Bowel Disease (IBD). The aim of our study was to validate the content of the IBD-Disk in a Greek cohort of IBD patients. METHODS: Two questionnaires [the IBD Disk and the IBD-Disability Index (IBD-DI)] were translated into Greek and administered to IBD patients at baseline visit, after 4 weeks and 6 months. Validation of the IBD Disk included measuring of concurrent validity, reproducibility, and internal consistency. RESULTS: A total of 300 patients were included at baseline and 269 at follow-up. There was a good correlation between the total scores of the IBD-Disk and IBD-DI at baseline (Pearson correlation 0.87, p < 0.001). Reproducibility of the total IBD-Disk score was very good [intra-class correlation coefficient (ICC), 95% confidence interval (CI) 0.89 (0.86-0.91)]. Cronbach's coefficient alpha for all items achieved 0.90 (95%CI 0.88-0.92), demonstrating a very good homogeneity of the IBD-Disk items. Female gender and extraintestinal manifestations were significantly associated with a higher IBD-Disk total score. CONCLUSIONS: The Greek version of the IBD-Disk proved to be a reliable and valid tool in detecting and assessing IBD-related disability in a Greek cohort of IBD patients.

Recent Advances in the Optimization of Anti-TNF Treatment in Patients with Inflammatory Bowel Disease.

Despite the evolution in inflammatory bowel disease (IBD) management during the last 20 years owing to the advent of new advanced therapies, anti-TNF agents still remain the cornerstone of therapy for both Crohn's disease and ulcerative colitis. However, this does not only secure favorable outcomes for patients considering the progressive disease character and the high likelihood of primary or secondary loss of response. Therefore, trying to reach a better treatment approach and maximize the benefits anti-TNF agents offer, optimization strategies should be examined. It has been indicated that optimizing treatment with anti-TNF enhances drug efficacy and has been associated with improved disease outcomes and a complication-free disease course. From this perspective, we aim to provide an overview of currently available data and recent advances in the practices of anti-TNF treatment optimization. Special focus has been given to the role of therapeutic drug monitoring (TDM), as well as the utility of combining anti-TNF with an immunomodulator and the treat-to-target approach.

Patients With Inflammatory Bowel Diseases Have Impaired Antibody Production After Anti-SARS-CoV-2 Vaccination: Results From a Panhellenic Registry.

BACKGROUND: Four EMA-approved vaccines against SARS-CoV-2 are currently available. Data regarding antibody responses to initial vaccination regimens in patients with inflammatory bowel diseases (IBD) are limited. METHODS: We conducted a prospective, controlled, multicenter study in tertiary Greek IBD centers. Participating patients had completed the initial vaccination regimens (1 or 2 doses, depending on the type of COVID-19 vaccine) at least 2 weeks before study enrolment. Anti-S1 IgG antibody levels were measured. Demographic and adverse events data were collected. RESULTS: We tested 403 patients (Crohn's disease, 58.9%; male, 53.4%; median age, 45 years) and 124 healthy controls (HCs). Following full vaccination, 98% of patients seroconverted, with mRNA vaccines inducing higher seroconversion rates than viral vector vaccines (P = .021). In total, IBD patients had lower anti-S1 levels than HCs (P < .001). In the multivariate analysis, viral vector vaccines (P < .001), longer time to antibody testing (P < .001), anti-TNFα treatment (P = .013), and age (P = .016) were independently associated with lower anti-S1 titers. Vedolizumab monotherapy was associated with higher antibody levels than anti-TNFα or anti-interleukin-12/IL-23 monotherapy (P = .023 and P = .032). All anti- SARS-CoV-2 vaccines were safe. CONCLUSIONS: Patients with IBD have impaired antibody responses to anti-SARS-CoV-2 vaccination, particularly those receiving viral vector vaccines and those on anti-TNFα treatment. Older age also hampers antibody production after vaccination. For those low-response groups, administration of accelerated or prioritized booster vaccination may be considered.

Thisis a multicenter study on IBD patients after COVID-19 vaccination and anti-S1 IgG antibody levels measurement. Patients with IBD have lower antibody responses than healthy controls, particularly those receiving viral vector vaccines and those on anti-TNFα or combination treatment.

Active smoking is associated with the development of adverse events of biological therapy in patients with inflammatory bowel disease.

INTRODUCTION: Smoking has been associated with lower levels of anti-TNF agents, higher antibodies and a reduced response to anti-TNF in patients with inflammatory bowel disease (IBD). The aim of this study was to investigate the possible association between smoking and adverse events (AEs) of biologics in patients with IBD. MATERIAL AND METHODS: Consecutive IBD patients under biologics from a prospective, longitudinal registry of a tertiary center were included. A specially designed questionnaire including a wide range of AEs associated with biologics was also used. RESULTS: A total of 147 patients with IBD under biologics [median age (IQR) 46 (32.5-56) years, Crohn's disease (CD) 109 (74%), female 51 (35%), under combination with immunosuppressants 60 (41 %), under intensified biologic therapy 50 (34%), under anti-TNF 132 (89%), vedolizumab 11 (7.5%), ustekinumab 3 (2%)] who had completed the questionnaire forms for AEs were included. There were 52 (35%) active smokers and 33 (22.5%) ex-smokers. The prevalence of all AEs was 88% in smokers, 87% in ex-smokers and 79% in nonsmokers. Active smoking was significantly associated with the presence of arthralgias and skin rashes ( P = 0.01 and 0.002, respectively). These correlations were the same for the CD and ulcerative colitis (UC), except for arthralgias where there was a significant correlation only with CD ( P = 0.001). There were no significant associations between smoking and other AEs ( P > 0.05). CONCLUSION: Active smoking is associated with the development of dermatological manifestations (both in UC and CD) and arthralgias (in CD) in IBD patients under biologics.

Elevated serum globulin fraction as a biomarker of multiyear disease severity in inflammatory bowel disease.

Background: Serum protein reflects albumin and globulin levels, both of which can be altered in inflammatory bowel disease (IBD). The implications of a high globulin fraction in IBD are unknown. We hypothesized that a high globulin fraction may function independently of albumin as a biomarker of disease severity in IBD patients over a multiyear period. Methods: This was an observational study from a prospective IBD registry of a tertiary care center. High globulin fraction was defined as an elevated globulin level >4 g/dL. Data collected included patient demographics, medication exposures, quality-of-life scores, disease activity, emergency department visits, telephone calls, hospitalizations, and IBD-related surgeries over a 4-year period. Comparisons between patients with a high globulin fraction and those without were performed using Pearson's chi-squared, Student's and Mann-Whitney tests. Multivariate analyses were used to assess the relationship between high globulin fraction and healthcare utilization. Results: A total of 1767 IBD patients with a 4-year follow up were included: 53.5% female, mean age 48.4±15.1 years, and 65.4% with Crohn's disease. Of these patients, 446 (25.2%) presented with elevated globulin fraction. Patients with a high globulin fraction were more likely to be hospitalized during the study period. This result remained significant after multivariate analysis for both Crohn's disease patients and those with ulcerative colitis. Conclusion: A high globulin fraction is independently associated with greater disease severity and healthcare utilization in IBD patients, and may function as a routinely available biomarker of a more severe future disease trajectory.

Abdominal aortic calcification in patients with inflammatory bowel disease: does anti-tumor necrosis factor α use protect from chronic inflammation-induced atherosclerosis?

BACKGROUND/AIMS: Abdominal aortic calcium (AAC) deposition has been suggested as a marker of early atherosclerosis. There is no published data on the evaluation of AAC in inflammatory bowel disease (IBD). METHODS: AAC was quantified by computed tomography or enterography scans performed in 98 IBD patients and 1:1 age and sex matched controls. AAC deposition was correlated with IBD characteristics, disease activity or severity parameters, laboratory tests and cardiovascular disease (CVD) risk factors. RESULTS: Moderate-severe grade of AAC was found in 35.7% of IBD patients compared to 30.6% of controls (P= 0.544). IBD with CVD and ulcerative colitis patients had significantly higher rates of more severe atherosclerotic lesions (P= 0.001 and P= 0.01, respectively). AAC deposition was similarly distributed in age groups ( < 45, 45-64, and ≥ 65 years) among patients and controls. Multivariate analysis after excluding CVD risk confounders for non-CVD patients found extensive disease (P= 0.019) and lifetime steroids (P= 0.04) as independent risk factors for AAC. Anti-tumor necrosis factor α (TNF-α) use was negatively associated with AAC deposition in non-CVD IBD patients (odds ratio, 0.023; 95% confidence interval, 0.001-0.594; P= 0.023). CONCLUSIONS: More than one-third of IBD patients have moderate to severe AAC. Better control of inflammation with anti-TNF-α agents seems to protect IBD patients from ACC deposition and subsequent atherosclerosis.

IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis: The PROCTRIAL Consensus.

BACKGROUND & AIMS: Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the Definition and endpoints for ulcerative PROCtitis in clinical TRIALs initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults. METHODS: Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters. RESULTS: The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity was proposed. Secondary endpoints that should be evaluated include endoscopic remission, histologic remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life. CONCLUSIONS: In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the Definition and end points for ulcerative PROCtitis in clinical TRIALs consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials.

Real-World Use and Adverse Events of SARS-CoV-2 Vaccination in Greek Patients with Inflammatory Bowel Disease.

Since inflammatory bowel disease (IBD) patients were excluded from vaccine authorization studies, limited knowledge exists regarding perceptions and unfavorable effects of COVID-19 vaccination in this group. We aimed to investigate the real-world use and adverse events (AEs) of COVID-19 vaccines in Greek IBD patients. Fully vaccinated IBD patients followed in Greek centers were invited to participate. All patients filled out an anonymous online survey concerning the vaccination program, which included information regarding demographics, clinical characteristics, treatment, vaccination perceptions and potential AEs. Overall, 1007 IBD patients were included. Vaccine hesitancy was reported by 49%. Total AEs to vaccination were reported by 81% after dose 1 (D1) and 76% after dose 2 (D2), including isolated injection site reactions (36% and 24% respectively). Systemic AEs were more common after D2 (51%, D2 vs. 44%, D1, p < 0.0001). Very few patients reported new onset abdominal symptoms (abdominal pain 4% (D1), 6% (D2) and diarrhea 5% (D1), 7% (D2)). There were no serious AEs leading to emergency room visit or hospitalization. In multivariate analysis, AEs occurrence was positively associated with young age and female gender (p < 0.0005 for both doses), whereas inactive disease was negatively associated with AE in D1 (p = 0.044). SARS-CoV-2 vaccination in Greek IBD patients demonstrated a favorable and reassuring safety profile.

Effect of antinuclear antibodies on pharmacokinetics of anti-TNF therapy in patients with inflammatory bowel disease.

PURPOSE: The detection of antinuclear antibodies (ANA) in serum of patients with inflammatory bowel disease (IBD) has been associated with a worse response to anti-TNF therapy and the development of cutaneous or arthritic manifestations. The aim of this study was to investigate a possible association of serum ANA with infliximab (IFX) and adalimumab (ADA) trough levels (TLs) and anti-drug antibodies in IBD patients treated with IFX or ADA. METHODS: Consecutive IBD patients under maintenance therapy with IFX or ADA in whom there was at least one available measurement of anti-TNF TLs, antibodies to IFX or ADA, and ANA in serum were included. The correlation of ANA positivity with demographics, clinical characteristics, treatment, TLs and anti-drug antibodies, of all patients was analyzed. RESULTS: One hundred two IBD patients under maintenance therapy with IFX or ADA were enrolled. Of these, 53 (52%) were ANA positive with 28 (27.5%) positive also to anti-ds-DNA in serum. In the univariate analysis ANA positivity was found to be correlated with age (P = 0.008), female gender (P = 0.03), duration of treatment (P = 0.06), arthralgias (P = 0.04) and TLs (P = 0.005). However, in multivariate logistic regression analysis only age and TLs remained significantly associated with the presence of ANA positivity (P = 0.04 and P = = 0.006, respectively). No significant association of ANA positivity with the development of cutaneous or rheumatological manifestations was found. CONCLUSIONS: In IBD patients under maintenance therapy with anti-TNF ANA positivity is associated with lower TLs. The clinical significance of this finding remains to be defined in future larger prospective studies.

Endpoints for extraintestinal manifestations in inflammatory bowel disease trials: the EXTRA consensus from the International Organization for the Study of Inflammatory Bowel Diseases.

Extraintestinal manifestations occur frequently in patients with inflammatory bowel disease (IBD) and remain a diagnostic and therapeutic challenge. The aim of the Endpoints for Extraintestinal Manifestations in Inflammatory Bowel Disease Trials (EXTRA) initiative was to achieve international expert consensus on how to assess these manifestations in IBD trials. A systematic literature review was done to identify methods to diagnose extraintestinal manifestations in patients with IBD and measure treatment outcomes. A consensus meeting involving a panel of 41 attendees, including gastroenterologists and referral specialists, was held on March 31, 2021, as part of an International Organization for the Study of Inflammatory Bowel Diseases initiative. The panel agreed that a specialist's expertise is needed to confirm the diagnosis of extraintestinal manifestations before the inclusion of a patient in IBD trials, except for axial spondyloarthritis, for which typical symptoms and MRI can be sufficient. Easy-to-measure endpoints were identified to assess the response of extraintestinal manifestations to treatment without needing specialist involvement. For uveitis, peripheral spondyloarthritis, and arthralgia, endpoint measurements need specialist expertise. The timing of endpoint measurements was discussed for individual extraintestinal manifestations. The EXTRA consensus proposes guidelines on how to thoroughly evaluate extraintestinal manifestations within IBD trials, and recommends that these guidelines are implemented in future trials to enable prospective assessment of these manifestations and comparison between studies.

Monocytosis Is a Biomarker of Severity in Inflammatory Bowel Disease: Analysis of a 6-Year Prospective Natural History Registry.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with alterations of the innate and adaptive immune systems. Monocytes respond to inflammation and infection, yet the relationship between monocytosis and IBD severity is not fully understood. We aimed to characterize the prevalence of monocytosis in IBD and the association between monocytosis and disease severity and IBD-related health care utilization. METHODS: We used a multiyear, prospectively collected natural history registry to compare patients with IBD with monocytosis to those without monocytosis, among all patients and by disease type. RESULTS: A total of 1290 patients with IBD (64.1% with Crohn disease; 35.9% with ulcerative colitis) were included (mean age 46.4 years; 52.6% female). Monocytosis was found in 399 (30.9%) of patients with IBD (29.3% with Crohn disease; 33.9% with ulcerative colitis). Monocytosis was significantly associated with abnormal C-reactive protein level and erythrocyte sedimentation rate, anemia, worse quality of life, active disease, and increased exposure to biologics (all P < 0.001). Compared with patients without monocytosis, patients with monocytosis had a 3-fold increase in annual financial health care charges (median: $127,013 vs. $32,925, P < 0.001) and an increased likelihood of hospitalization (adjusted odds ratio [AOR], 4.5; P < 0.001), IBD-related surgery (AOR, 1.9; P = 0.002), and emergency department (ED) use (AOR, 2.8; P < 0.001). Patients with monocytosis had a shorter time to surgery, hospitalization, and ED visit after stratifying by disease activity (all P < 0.05). CONCLUSIONS: Patients with IBD with monocytosis, regardless of disease type, are at increased risk for worse clinical outcomes, hospitalization, surgery, and ED use. Peripheral monocytosis may represent a routinely available biomarker of a distinct subgroup with severe disease.