Efficacy of risankizumab by baseline clinical, biochemical, and endoscopic disease severity in moderately to severely active Crohn's disease

Background: Risankizumab (RZB), a p19-anti-interleukin-23 monoclonal antibody, has demonstrated efficacy as induction and maintenance therapy in patients with moderately to severely active Crohn's disease (CD). This post hoc analysis evaluates the efficacy of induction and maintenance RZB therapy by baseline clinical, biochemical, and endoscopic disease severity. Method(s): In the ADVANCE (NCT03105128) and MOTIVATE (NCT03104413) studies, patients with moderately to severely active CD and intolerance/inadequate response to >= 1 biologic (both studies) and/or conventional therapy (ADVANCE) were randomized to receive intravenous (IV) RZB induction therapy or placebo (PBO) for 12 weeks. Patients achieving stool frequency and/or abdominal pain score clinical response to 12 weeks of induction therapy were rerandomized in the FORTIFY (NCT03105102) study to receive subcutaneous (SC) maintenance RZB (180 mg or 360 mg) or PBO (withdrawal). Clinical and endoscopic endpoints were evaluated by baseline disease characteristics (Crohn's Disease Activity Index [CDAI: <= 300, > 300], highsensitivity C-reactive protein [hs-CRP: < 10 mg/L, >= 10 mg/L], and Simple Endoscopic Score for Crohn's Disease [SES-CD: 6-15, > 15]). Induction analyses included patients who received RZB 600 mg or PBO;data from the ADVANCE and MOTIVATE studies were pooled. Nonresponder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used. Result(s): The induction analysis included 527 patients who received RZB 600 mg IV and 362 patients who received PBO. Patients treated with RZB 600 mg IV achieved significantly higher response rates vs PBO at week 12, regardless of subgroup (P < .05 for all;Figure 1). In the maintenance study, patients treated with SC RZB continued to achieve higher response rates vs the PBO (withdrawal) group at week 52 regardless of subgroup (P was not < .05 for all;Figure 2). Improvements in clinical and endoscopic outcomes were generally observed from weeks 12 to 52 with RZB treatment across all subgroups. Response rates were generally similar across subgroups in both induction and maintenance studies;endoscopic remission and ulcer-free endoscopy (resolution of ulcer) rates were numerically lower for patients with increased inflammation (hs-CRP > 10 mg/mL) and higher endoscopic activity (SES-CD > 15). Conclusion(s): RZB induction therapy resulted in higher response rates for clinical and endoscopic outcomes compared with PBO at week 12, regardless of baseline clinical, biochemical, and endoscopic disease severity. RZB also showed durable efficacy with continued RZB maintenance therapy, supporting the long-term use of RZB for patients across a range of baseline disease severity and activity.

Lack of seroconversion following COVID-19 vaccination, but not treatment, is an independent risk factor for breakthrough SARS-CoV-2 infection in patients with inflammatory bowel disease: Data from ESCAPE -an IG-IBD Study

Background: As patients with immune conditions were excluded from COVID-19 vaccine clinical trials, it is important to accumulate realworld data in this setting, particularly to identify those who would benefit from repeated doses. Method(s): Effectiveness and Safety of COVID-19 Vaccine in Patients with Inflammatory Bowel Disease (IBD) Treated with Immunomodulatory or Biological Drugs (ESCAPE) is a prospective, multicentre, observational study assessing effectiveness and safety of COVID-19 vaccines in patients with IBD (ClinicalTrials.gov ID: NCT04769258). Here we present data on the rate of breakthrough SARS-CoV-2 infections in the timeframe between 14 days after the second dose and the third dose of COVID-19 vaccine (or a maximum of 9 months from the second dose). The risk factors for SARS-CoV-2 infection, including lack of seroconversion (cut-off for IgG anti-SARS-CoV-2: OD 0.28) and IgG anti-SARS-CoV-2 levels after 8 weeks from the second dose, and treatment for IBD, were assessed. Result(s): Out of the 1076 patients with IBD enrolled in the ESCAPE study, data on breakthrough SARS-CoV-2 infection were available in 953 cases. Most of the patients received homologous, doubledose mRNA-based vaccines (BNT162b2 or mRNA-1273: 99.2%). Seroconversion was reported in 92.7% of cases (median OD 1.60 [IQR 0.8-3.6]), while SARS-CoV-2 infection was documented in 95 patients (10.0%), of whom 9 died. At multivariable regression analyses, age (OR 0.97, 95% CI 0.96-0.99;p<0.001) being former smoker (OR 2.23, 95% CI 1.26-3.88;p=0.005), and lack of seroconversion (OR 0.42, 95% CI 0.20-0.99;p=0.034) were independent predictors of SARS-CoV-2 infection. Conversely, none of the treatments for IBD was associated with breakthrough SARS-CoV-2 infection. Notably, all 9 patients who died had reported seroconversion after the second dose. Conclusion(s): IBD patients without seroconversion after COVID-19 vaccines are at increased risk for SARS-CoV-2 infection, while medications for IBD had no impac.

Serum Proteomics and Metabolomics Study on Susceptibility to Sars-Cov-2 Infection in Ibd Patients

Introduction: Since 2020 COVID-19 pandemic has spread throughout the world and became an ongoing global health crisis due to SARS-CoV-2 virus. Elderly and pre-existing disorders including hypertension, heart problems, diabetes, cancer, autoimmune diseases and IBD are found associated with an increased risk of COVID-19. Although COVID-19 leads to mild flu-like symptoms in the majority of patients, the disease may cause severe complications and death. To date, a few clinical studies suggested that IBD and/or immunomodulation may reduce the susceptibility to COVID-19;however, the mechanisms through which this is happening is largely unknown. Aims & Methods: Aim of this study is to investigate the effects of IBD and different therapies on the risk of SARS-CoV-2 infection and COVID-19 severity through serum proteomics and metabolomics. Between April 2020 and April 2022, 238 IBD patients (N=145 Crohn disease, N=93 Ulcerative colitis) and 45 healthy controls (HC) of the North Italy area were enrolled and serum samples were collected. To evaluate the exposure to SARSCoV- 2, both clinical data were collected and seroprevalence of anti-SARSCoV- 2 Ab were analyzed by means of multiplex technology, the BioPlex 2200 Sars-Cov-2 IgG Panel (biorad, Italy). Serum samples underwent untargeted metabolomics analysis and the frequency of a serum metabolomics signature associated with protection were evaluated in IBD compared to HC and also between anti-TNF and Vedolizumab biological therapies for IBD patients. Result(s): The seroprevalence of anti-SARS-CoV-2 Ab in IBD cohort (22/238) indicates an overall lower incidence of COVID-19 in comparison with the general population of Lombardy. Our data indicated that IBD patients in treated with biologic drugs as anti-TNF (10,5%) and Vedolizumab (7,5%) have a lower incidence than IBD patients treated with conventional therapies (28,0%). Accordingly, we observed that serum metabolomics signature associated with protection was more frequent in IBD patients treated with anti-TNF (N=50, 70%), and with Vedolizumab (N=57, 85%) than healthy controls (N=45, 50%). The metabolomic protective profile is characterized by the presence of fat-soluble Tocopherols family members and Cholecalciferol and also of omega-3 and omega-6 polyunsaturated fatty acid. Conclusion(s): Our study indicates that IBD population treated with biologics has an overall lower risk to contract SARS-CoV-2 infection and a serum proteomic/metabolomic protection profile. The increased presence in IBD patients of radical scavengers such as tocopherols which are incorporated into cell membranes and protect against oxidative damage and anti-inflammatory and immunomodulating fatty acids suggest a better response to SARS-CoV-2 infection. Also increased levels of omega;-3 interfere with the entry of the virus by modulating the Lipid Rafts where ACE2 and TMPRSS2 are mainly expressed and PUFAs inhibit the attachment of SARS-CoV-2 virions to the human ACE2 receptor by interacting directly with the RBD sequence. Mechanistically understanding how this protection profile exerts its effects on COVID-19 severity might shed light on potential targets to increase resistance in higher risk subgroups of patients.

Exploring the Trascriptomic Underpinning the Effect of Biological Therapies on Sars-Cov-2 Susceptibility in Inflammatory Bowel Disease (Ibd) Patients

Introduction: The current pandemia is due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that was originally identified in China in 2019, when numerous cases of atypical pneumonia were reported. Elderly and pre-existing disorders including hypertension, heart problems, diabetes, cancer, autoimmune diseases and IBD are found associated with an increased risk of COVID-19. A few clinical studies suggested that IBD and immunomodulation may reduce the susceptibility to COVID-19;however, the molecular mechanisms are not fully revealed. Aims & Methods: In this study, we attempted to identify a transcriptomic signature as candidate of the effects of IBD and different therapies on the risk of SARS-CoV-2 infection and COVID-19 severity through colonic tissue gene expression. In 2020-2022, 192 IBD patients, 115 Crohn disease (CD), 77 Ulcerative colitis (UC) and 36 Healthy Controls (HC) of the North Italy area were enrolled. Colon biopsies from inflamed and non-inflamed mucosa were collected from IBD patients and healthy mucosa samples were collected from HC. To evaluate the exposure to SARS-CoV-2, clinical data were collected and seroprevalence of anti-SARS-CoV-2 Ab were analyzed by means of multiplex technology with BioPlex 2200 Sars-Cov-2 IgG Panel (biorad, Italy). Gene expression analysis of ACE2, TMPRSS2, TMPRSS4, ADAM17 were performed by qPCR in biopsies of the three experimental groups. Result(s): In IBD patients cohort the seroprevalence of anti-SARS-CoV-2 antibodies indicates an overall lower incidence of COVID-19 in comparison with the general population of Lombardy, and also a lower incidence in IBD patients in biological therapies vs. conventional ones. Gene expression analysis of the proteins involved in SARS-CoV-2 entry indicated that IBD patients treated with anti-TNF (N=72) had a lower mucosal level of SARS-CoV-2 receptor ACE2 and its sheddase ADAM17 than non-IBD subjects along with higher expression of the proteases TMPRSS2 and TMPRSS4. Moreover, vedolizumab-treated patients (N=40) showed a significant lower expression of ACE2, TMPRSS2 and TMPRSS4 than controls, whereas ADAM17 levels were similar. Conclusion(s): Data presented in our study suggest that the biologic-treated IBD population has an overall lower risk of contracting SARS-CoV-2 infection. Colonic expression of proteins involved in SARS-CoV-2 virus entry suggested an additional protective mechanism. Understanding the association of this protection profile with COVID-19 severity and the mechanisms of virus entry into the colon could reveal resistance pathways in higher-risk patient subgroups.

Reduced Humoral Response to Two Doses of Covid-19 Vaccine in Patients with Inflammatory Bowel Disease: Data from Escape-Ibd, an Ig-Ibd Study

Introduction: Patients on immunosuppressive drugs have been excluded from COVID-19 vaccines trials, creating concerns regarding their efficacy in this setting. Aims & Methods: Effectiveness and Safety of COVID-19 Vaccine in Patients with Inflammatory Bowel Disease (IBD) Treated with Immunomodulatory or Biological Drugs (ESCAPE-IBD) is a prospective, multicentre study promoted by the Italian Group for the study of Inflammatory Bowel Disease. We present data on serological response eight weeks after the second dose of COVID-19 vaccination in IBD patients and healthy controls (HCs). Result(s): 1076 patients with IBD and 1126 HCs were analyzed. Seropositivity for anti-SARS-CoV-2 IgG was reported for most IBD patients, even if with a lesser rate compared with HCs (92.1% vs. 97.9%;p<0.001). HCs had higher antibody concentrations (median OD 8.72 [IQR 5.2-14-2]) compared to the whole cohort of IBD patients (median OD 1.54 [IQR 0.8-3.6];p<0.001) and the subgroup of IBD patients (n=280) without any treatment or on aminosalicylates only (median OD 1.72 [IQR 1.0-4.1];p<0.001). IBD patients treated with anti-TNFs showed significantly lower median anti-SARS-CoV-2 IgG levels compared with those without any treatment or on aminosalicylates only (OD 1.30 [IQR 0.7-3.0] vs.1.72 [IQR 1.0-4.1];p<0.001), those treated with Vedolizumab (OD 1.78 [IQR 1.1-4.1];p=0.001), and Ustekinumab (OD 1.71 [IQR 0.9-4.9];p=0.03). Conclusion(s): Although most IBD patients showed seropositivity after two doses of COVID-19 vaccines, the magnitude of the humoral response was significantly lower than in HCs. Differently from other studies, these findings seem to be mostly unrelated to the use of immune-modifying treatments. Regarding COVID-19 vaccination, patients with IBD should be regarded as a whole as a "frail" category, therefore requiring booster/additional doses of COVID-19 vaccine.

Evaluation of factors associated with trust in telemedicine in patients with inflammatory bowel disease during COVID-19 pandemic: a multicenter cross-sectional survey.

OBJECTIVE: Telemedicine (TM) has had a powerful impact in recent years, particularly on managing chronic diseases such as inflammatory bowel disease (IBD). Knowing patients' expectations and concerns is essential to increase their confidence in this mode of medical care. PATIENTS AND METHODS: We interviewed a large cohort of IBD patients enrolled at two Italian tertiary referral centers to investigate their trust in TM. RESULTS: A total of 376 patients completed the survey and were included in the study: 293 (77.9%) considered TM valuable for managing their disease, and 307 (85%) wanted to have TM service at their center. However, only 99 patients (26.3%) believed that TM guarantees the same level of care as the in-person visit. Among the socio-demographic variables, those independently associated with trust in TM were the higher education qualification (p=0.02) and the level of competence in information and communication technologies (ICT) (p=0.03). CONCLUSIONS: Our findings highlighted the importance of equipping IBD patients with basic ICT skills to utilize TM services and increase their confidence in ICT with the help of caregivers. Additionally, to improve the perceived value of TM, it will be helpful to use additional tools such as telemonitoring of disease activity using patients' reported outcomes or remote measurement of fecal calprotectin.

ISCHEMIC STROKE SHORTLY AFTER VACCINATION AGAINST SARS-COV-2: A CASE-CONTROL STUDY

Background and aims: Vaccination against SARS-CoV-2 has been associated with rare occurrences of cerebral venous thromboses. Very little data exist about arterial ischemic strokes. We have assessed the features of ischemic strokes occurring shortly after vaccination against SARS-CoV-2 in the Cremona area, Italy. Methods: From February 1, to July 31, 2021, all patients with ischemic stroke within four weeks of vaccination against COVID-19 admitted to our stroke unit were consecutively collected, and their main features were compared with those of all other patients with ischemic strokes admitted during the same period. Results: Sixteen strokes shortly after vaccination were collected. They represented 10.5% of all ischemic strokes. Median interval from vaccination was 12 days (range 1-24). Fifteen (93.8%) had received the BNT162b2 (Pfizer-BioNTech) vaccine and 1 (6.2%) the ChAdOx1 nCoV- 19 (AstraZeneca). Two patients (12.5%) had mild thrombocytopenia on admission (128,000 and 142,000/ml), without any evidence of bleeding or venous thrombosis. Thrombolysis and/or thrombectomy were carried out in 4 cases (25.0%). When compared with 137 strokes without recent vaccination, none of the demographic, clinical, and laboratory features of post-vaccination strokes were significantly different. Conclusions: This is the largest description of ischemic strokes shortly after COVID-19 vaccination. Strokes features were mostly similar to those of other stroke patients. Thus, the relatively high percentage of such patients probably relates to the very high fraction of elderly people vaccinated against SARS-CoV-2 in the Cremona area, rather than to a consequence of vaccination. These data may also be useful to counsel patients about future vaccinations.

Willingness and hesitancy to the telemedicine in patients with inflammatory bowel disease during COVID-19 outbreak. Preliminary results of a survey in an Italian IBD Center

Background: Telemedicine is becoming a necessary tool for chronic disease management. Thanks to the wide diffusion of devices connecting to the World Wide Web, a large part of the population are now able to access to telemedicine services.Telemedicine is becoming a necessary tool for chronic disease management. Thanks to the wide diffusion of devices connecting to the World Wide Web, a large part of the population are now able to access to telemedicine services. The aim of this survey was to explore the willingness and hesitancy of patients with inflammatory bowel disease (IBD) to the use of telemedicine during COVD-19 outbreak. Methods: A paper-and-pencil questionnaire was proposed to all consecutive patients observed at our tertiary IBD center in San Giovanni Rotondo (Italy) from February to May 2021. The survey investigated 20 items that can be grouped into 5 areas: socio-demographic data, clinical data, informatics competence, devices and network utilized for the internet connection, attitude to the telemedicine, and the impact of COVID-19 pandemic. Results: A total of 156 patients completed the questionnaire (100 males). One hundred forthy-three patients (91.7%) were under 65 years and only 15 (9.6%) were graduates. Forthy-seven patients (30%) were single, 101 married (65%). Eighteen patients (11.5%) felt they had no IT skills. Eight patients (5.1%) had a previous experience of telemedicine. One hundred twenty-three patients (78.8%) consider the support of telemedicine useful for the management of their pathology and 134 (85.9%) would like the Center where they are followed up to have the possibility of offering a telemedicine service. One hundred three patients (66.0%) would like to have a teleconsultation with figures other than the Gastroenterologist. Ninety-seven patients (62.2%) agree that the ongoing coronavirus pandemic has a major impact on the need to implement telemedicine. Regarding the confidence with telemedicine, 106 patients (67.9%) were partially or totally agreeing telemedicine can properly resolve health problems, and 98 (62.8%) agree that technologies guarantee the privacy of the health data. One hundred twenty-five patients (80%) agree that telemedicine should be developed independently of the pandemic, however only 48 patients (31%) believe that telemedicine guarantee the same level of assistance of visit in presence. Conclusion: Italian IBD patients showed a positive attitude towards telemedicine and consider that useful for the management of their disease. The majority of patients would like the center where they are followed up offering a telemedicine service, regardless of the ongoing pandemic. However only one third of patients believe that telemedicine can offer the same level of assistance of in-presence visit.

Telemedicine in IBD patients: Results of a national survey of the Italian IBD patients' association (AMICI Onlus)

Background: Telemedicine is one of the major changes that clinicians have encountered over the past decade;in particular during the COVID-19 pandemic, televisits were rapidly implemented to guarantee patients' assistance, with the intention of Health Care Providers (HCPs) to continue to use them beyond the pandemic. The aim of our national survey was to evaluate the current usage of telemedicine for IBD patients from their perspective, investigating patients' impressions about telemedicine and factors affecting them through a Machine Learning (ML) analysis. Methods: In March 2021, the Italian IBD patients' association (AMICI Onlus) distributed to their members -through its mailing list and on social media platforms -an anonymous online questionnaire investigating the use of telemedicine. Socio-demographic and IBD characteristics were collected;the usage, patients' satisfaction and trust of telemedicine were assessed through Likert scales. ML tools -Decision Trees (DT) and Random Forest (RF) -were applied to identify the determinants of patient's perceptions about telemedicine;the produced RF ranking displays two indicators: %IncMSE and IncNodePurity. Results: Nine hundred and seventy-eight IBD patients (women 58.9%) from every Italian region completed the questionnaire. Among the respondents, 87 (8.9%) personally had a telemedicine experience;153 reported that their Centre performed a telemedicine service during the COVID-19 pandemic (24.2% televisits, 39.2% e-mails, 24.8% phone-calls, 3.9 % dedicated website, 7.9% others). Overall, 707 (72.3%) would trust a telemedicine service, 760 (77.7%) would like to have it also with another HCP (e.g., nutritionist, psychologist) and 778/961 (81%) would like to use telemedicine in the future (17 did not answer to this specific question);792 (81%) stated they thought useful to have the possibility to use telemedicine and 847 (86.6%) would like their Centre to offer them this facility. Considering this last question as the output at the DT, the variable which have been found to influence the most this patients' willingness is patient's perception of the usefulness of telemedicine in treating their disease, since it represented the root of the tree explaining the results. The RF rankings confirmed that this variable influenced the most patients' perception with the highest levels of %IncMSE and IncNodePurity(Figure 1). Conclusion: The practice of telemedicine in the management of IBD patients has not been very relevant throughout Italy so far (less than 10%), but more than four every five respondents would like to use telemedicine. Machine learning analysis shows that the perceived usefulness of telemedicine service is the key point for patients who would like it was a part of usual clinical practice.

IBD and COVID-19 in Italy: Comparisons between first and second pandemic wave

Background: Coronavirus disease 2019 (COVID-19), had two pandemic waves in 2020, respectively in April and November. In the general population, the first wave has been characterized by a higher prevalence in Northern Italy and a higher mortality rate compared to the second one. The aim of this study was to compare the characteristics of IBD patients and negative outcomes of COVID-19 (pneumonia, hospitalization, ventilatory support, death) between the two pandemic waves in Italy. Methods: Prospective observational cohort study. Patients with diagnosis of IBD and confirmed SARS-CoV-2 infection were enrolled. Differences between first and second wave were tested for significance using the Student's t test and Fisher's test, as appropriate. A two-tailed p value <0.05 was indicative of statistical significance. Results: We enrolled 937 IBD patients from 47 participating IBD centres across Italy (219 in the first wave, 718 in the second wave). There were no significant differences between the first and the second wave in terms of age (46.3 ± 16.0 vs. 44.1 ± 15.5 years, p=0.06) and gender (female 45.7% vs. 48.2%, p= 0.54). In the first wave, a lower percentage of patients was affected by Crohn's disease (CD): 92 (42.0%) vs. 399 (55.6%) (p<0.001) while no differences were observed for disease clinical activity: 97/219 (44.3%) vs. 280/718 (38.9%) in the first and second wave, respectively (p=0.18). Regarding biologic therapy, the percentage of patients on biologics in the two waves was similar: 119/219 (54.3%) vs. 393/718 (54.7%) (p=0.94), without differences in anti-TNFalpha, anti-integrins and anti-IL12/23 distribution. During the first wave, a significantly higher percentage of patients were from Northern Italy compared to Central-Southern Italy: 171/219 (78.1%) vs. 387/718 (53.9%), respectively (p<0.001). Overall, COVID-19 negative outcomes were significantly higher in the first wave compared to the second one: 110 (50.2%) vs. 95 (13.2%), respectively (p<0.001). Also the single negative outcomes were significantly higher in the first wave: 61/219 (27.8%) vs. 84/718 (11.7%) had pneumonia, 62/219 (28.3%) vs. 76/718 (10.6%) required hospitalization, 26/219 (11.9%) vs. 39/718 (5.4%) required ventilatory support, and 12/219 (5.5%) vs. 13/718 (1.8%) died (Figure 1). Conclusion: IBD patients had higher number of COVID-19 negative outcomes in the first wave than in second wave. In the first wave, a significantly higher percentage of patients were from Northern Italy, but no significant differences in negative outcomes were observed in comparison with those from Central- Southern Italy. Overall, findings in IBD population are coherent with those observed in the general population. (Table Presented).

Increased risk of ibd flare after sars-cov-2 infection. Whos the more guilty: Viral infection or therapy withdrawal?

Background: In the last year, the severe adult respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic has spread rapidly around the world. The interactions between SARS-CoV-2 and inflammatory bowel disease (IBD) are so far not fully understood. In particular, no studies evaluated the potential role of SARS-CoV-2 on IBD course. Indeed, it is known that viral infections can be act as triggers for IBD flare and it is reasonable that the possible drug discontinuation during SARS-CoV-2 infection could in turn lead to an IBD flare. Methods: This was a prospective, observational case-control study. From March 11th 2020 to June 30th 2020 we enrolled IBD patients with proven SARS-Cov-2 infection (cases) and IBD patients without SARS-CoV-2 infection matched for sex, age, diagnosis, therapy and clinical activity (controls). Cases and controls were followed-up at least for 6 months. Differences between case and control group were tested for significance using the Students t test and Fishers test, as appropriate. A two-tailed p value < 0.05 was indicative of statistical significance. Results: 219 IBD patients (127 UC, 58.0%) with SARS-CoV-2 infection and 219 IBD patients without SARS-CoV-2 infection were enrolled. Table 1 shows baseline features of the population. Among the 122 cases in clinical remission at the time of viral infection, 28 (22.9%) showed a disease flare;this percentage was significantly higher than that observed in controls: 12/137 (8.8%)(p=0.0018). Among patients with disease flare, there were no significant differences between cases and controls group in terms of age (42.3 ± 16.0 vs. 43.1 ± 15.4 years, p=0.44), gender (female 45.7% vs. 48.2%, p= 0.54), use of biologic therapies (p=0.83) and UC or CD diagnosis (p=0.06). Biologic therapy was temporary withdrawn more significantly in cases than in controls (68/202, 33.6% vs. 14/204, 6.9%) (p<0.001) and overall biologic therapy discontinuation was significantly associated with disease flare (OR 2.56, 95% CI 1.026.41, p=0.04). Conclusion: IBD patients with SARS-CoV-2 infection have an increased risk to have a clinical recurrence in short-term in comparison with IBD patients without SARS-CoV-2 infection. This increased risk could be due to the viral infection and/or to the temporary discontinuation of biologic therapies, because of infection.

Potential mechanisms linking biological therapies on SARS-CoV-2 susceptibility in Inflammatory Bowel Disease patients

Background: The current novel coronavirus (SARS-CoV-2) pandemic is an ongoing global health crisis, which represents an important challenge for the whole society and mankind. Patients with inflammatory bowel disease (IBD) are treated with immunosuppressive drugs that are usually associated with more severe viral infections. However, the effects of the different therapies on the risk of SARS-CoV-2 infection and Covid-19 severity in IBD patients are still under investigation. Methods: Between April 2020 and April 2021, 238 IBD patients (N=145 with Crohn disease and N=93 with Ulcerative colitis) of the North Italy area have been enrolled. Both serum samples (N=238 IBD patients and N=45 healthy donors) and colon biopsies from inflamed and non-inflamed mucosa (N=88 IBD patients N=20 non-IBD control) have been collected. To evaluate the exposure to SARS-CoV-2, both clinical data and seroprevalence of anti-SARS-CoV-2 Ab have been analyzed. Serum samples were analyzed by untargeted metabolomics analysis and the frequency of a serum metabolomics signature associated with protection were evaluated in IBD versus healthy donors. Moreover, gene expression analysis of key proteins for virus entry (ACE2, TMPRSS2, TMPRSS4, ADAM17) were analyzed by qPCR in the gut mucosa biopsies of IBD patients. Results: The seroprevalence of anti-SARS-CoV-2 Ab in our cohort of IBD patients (10/238) indicates an overall lower incidence of COVID-19 in comparison with the general population of Lombardy. Accordingly, we observed that the serum metabolomics signature associated with protection was more frequent in IBD patients treated with anti-TNF (N=50, 70%), than healthy controls (N=45, 50%). Gene expression analysis of the proteins involved in SARS-CoV-2 entry also indicated that IBD patients treated with anti-TNF (N=14) had a lower mucosal level of SARS-CoV-2 receptor ACE2 and its sheddase ADAM17 than non-IBD subjects along with higher expression of the proteases TMPRSS2 and TMPRSS4. Moreover, vedolizumab-treated patients (N=7) showed a significant lower expression of ACE2, TMPRSS2 and TMPRSS4 than controls, whereas ADAM17 levels were similar. Conclusion: Our study indicates that IBD population treated with biologics has an overall lower risk to contract SARS-CoV-2 infection. Future studies to gather the mechanisms underpinning the effects of biologics on the expression of the proteins involved in SARS-CoV-2 viral entry in association with the specific metabolomics signature of viral susceptibility might shed light on potential targets to increase resistance in higher risk subgroups of patients.

TELEMEDICINE IN GASTROENTEROLOGY: A STUDY ON FEASIBILITY AND PATIENTS’ TRUST DURING COVID-19 PANDEMIC

Background and Aim Telehealth includes both health care delivery (often identified as telemedicine) in terms of disease diagnosis or treatment and several other services, such as prevention, education and public health promotion.1 During the recent COVID-19 pandemic, worldwide telemedicine has enabled many patients with chronic diseases to get access to remote assistance, since it has emerged as the ideal solution to overcome the restrictions to perform regular non-urgent follow-up visits to chronic patients and to continue patients’ assistance. Some positive reports on the use of telemedicine in gastroenterology among healthcare providers and patients have been published, but a patient’s trust perspective about video-consultations has been missing to date.2-5 Our study aimed at ascertaining our gastroenterological patients’ trust in video-consultations during the COVID-19 pandemic. Material and Methods At our Gastroenterology Unit in Milan (Italy), which is a tertiary referral center for Inflammatory Bowel Diseases (IBD) and Celiac Disease (CeD), telemedicine was used in place of on-site follow-up visits scheduled but not provided during the COVID-19 pandemic: all IBD and CeD outpatients received a phone call, while video-consultations were performed to patients with mild-to-moderate symptoms, with bio-umoral alterations or as needed for those patients who requested it. The patient’s trust in telemedicine was assessed through an adapted version of the PAtient Trust Assessment Tool (PATAT) question-naire.6 The primary endpoint was expressed as a percentage greater than 75% of patients giving a score of at least 4 out of 5 in a Likert Scale for three selected key statements about telemedicine.Results One hundred eighty-eight out of 218 scheduled (86.2%) video-consultations were performed. Among the 188 visits, 163 (86.7%) questionnaires were compiled. The primary endpoint of trust in the telemedicine service was achieved in 95.2%, 89.7% and 87.3% of the respondents for the three selected key statements (trust the service, its capability to solve clinical problems, ease to use).Conclusion During the COVID-19 pandemic our results showed that most of our IBD and CeD patients accepted and trusted video-consultations as an alternative to the traditional in-person examination.References: 1) Ray Dorsey E et al. N. Engl. J. Med. 2016;375:154–161. 2) Lauren A. G., Raymond K. Current Gastroenterology Reports (2020) 22: 12 3) De Jong, M. J. et al. Clinical Gastroenterology and Hepatology 2020;18:1744–1752 4) Lees CW et al. Gastroenterology. 2020 Sep;159(3):805-808.e1. 5) Allocca M et al. Clin Gastroenterol Hepatol 2020;18:1882–1883. 6) Velsen, L. V. et al, H. Int. J. Med. Inform 2017;97:52–58.(Figure presented)

DETERMINANTS OF COVID-19 VACCINE HESITANCY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE (IBD): RESULTS OF A NATIONAL SURVEY OF THE ITALIAN IBD PATIENTS’ ASSOCIATION (AMICI ONLUS)

Background and aim: Vaccine hesitancy, the delay in acceptance or refusal of vaccination despite its availability, threatens the control of infectious diseases. COVID-19 vaccination has been recommended by national and international organizations in patients with Inflammatory Bowel Diseases (IBD). The aim of the study was to evaluate COVID-19 vaccine hesitancy in a population of Italian patients with IBD. Materials and methods: In February 2021 an online questionnaire focused on COVID-19 vaccine was proposed to a representative sample of Italian IBD patients. Socio-demographic characteristics, IBD features, lifestyle, perception of COVID-19, general attitude towards vaccinations and to COVID-19 vaccines were investigated. Patients were divided into willing, hesitant and refusive towards COVID-19 vaccine. The hesitation reasons were investigated. The associations between baseline characteristics and willingness (determinants) were evaluated by calculating crude and adjusted Odds Ratio (AdjOR) with 95% confidence intervals (CI). Results: A total of 1252 surveys were collected. 1005 (80.3%), 222 (18.1%) and 33 (2.63%) patients were defined as willing, hesitant and refusive, respectively. The baseline characteristics are shown below. Concerns for vaccine adverse effects constituted the main reason for refusal (73.4%) (Figure). 49.1% of hesitant patients reported that presence of IBD exerted an influence on their answer. Among the patients willing to be vaccinated whenever possible, 78.2% (786) thought that their IBD represented a valid motivation to access vaccination with priority. Willingness to COVID-19 vaccine was significantly associated with adherence to previous vaccinations (AdjOR 17.6;95% CI: 11.4-27.2), male gender (1.68 95%;CI: 1.16-2.43), graduation degree (1.48;95%;CI: 1.03-2.13), perceived higher risk of COVID-19 becaues of IBD (1.47;95% CI: 1.05-2.08), alcohol intake (1.69;95% CI: 1.16-2.45). Conversely, the hesitancy was significantly associated with complementary and alternative medicine use (0.58;95% CI: 0.36-0.92). 54.5% of patients were under the impression to have a higher risk of COVID-19 and 31.8% to have a more severe course due to their IBD. (figure presented) Conclusions: Most IBD patients would accept COVID-19 vaccines, although one in five was hesitant, primarily due to fear of adverse events. Knowledge of determinants and reasons for COVID-19 vaccination acceptance or refusal could be key in developing targeted communication strategies to fight vaccine hesitancy, also in the future for general vaccinations.

THE EMERGING ROLE OF TELEMEDICINE IN GASTROENTEROLOGY DURING THE COVID-19 PANDEMIC: A STUDY ON ITS FEASIBILITY AND PATIENTS’ TRUST

Background and aim: During the on-going COVID-19 pandemic telemedicine has enabled many patients with chronic diseases worldwide to get access to remote assistance. Telemedicine has emerged as the ideal solution to overcome the restrictions in place on performing regular non-urgent follow-up visits for chronic patients and continuing patients’ assistance. Some positive reports on the use of telemedicine in gastroenterology among healthcare providers and patients have been published, but a patient’s trust perspective about televisits has so far been unavailable. Our study aimed at ascertaining telemedicine feasibility and gastroenterological patients’ trust in televisits during the COVID-19 pandemic. Materials and methods: At our Gastroenterology Unit in Milan (Italy), which is a tertiary referral center for Inflammatory Bowel Diseases (IBD) and Celiac Disease (CeD), telemedicine was used in place of on-site follow-up visits scheduled but not provided during the COVID-19 pandemic. All IBD and CeD outpatients were contacted by phone and televisits were arranged for patients with mild-to-moderate symptoms, with bio-umoral alterations or as needed for those who requested it. The patients’ trust in telemedicine was assessed through an adapted version of the PAtient Trust Assessment Tool (PATAT) questionnaire. The primary endpoint was expressed patient’s trust as assessed through the questionnaire. The secondary endpoint was feasibility and acceptance of televisits. Results: A total 188 out of 218 scheduled (86.2%) televisits were performed and among these a total of 163 (86.7%) questionnaires compiled was accomplished. The primary endpoint of trust in the telemedicine service was achieved in 95.2%, 89.7% and 87.3% of the respondents for the three selected key statements about trust in the telemedicine service, its capability to solve clinical problems and ease to use, respectively.(figure presented) Conclusions: Our results showed that during the COVID-19 pandemic televisits were feasible for most of our patients with chronic gastroenterological diseases, and that most patients accepted and trusted televisits as an alternative to the traditional in-person examination