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Background: Patients on immunosuppressive drugs have been excluded from COVID-19 vaccines trials, creating concerns regarding their efficacy. Aims: To explore the humoral response to COVID-19 vaccines in patients with inflammatory bowel disease (IBD) 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). Results: 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

Tofacitinib is approved for several immune-mediated inflammatory diseases, but safety concerns have recently been raised. We searched PubMed (accessed on 27 February 2023) for original articles regarding tofacitinib’s cancer risk when used for rheumatoid arthritis, ulcerative colitis, Crohn’s disease, psoriatic arthritis, and ankylosing spondylitis. Of the 2047 initial records, 22 articles describing 26 controlled studies (including 22 randomized controlled trials) were selected. In the comparison between tofacitinib and any control treatment, the relative risk (RR) for any cancer was 1.06 (95% CI, 0.86–1.31; p = 0.95). In separate comparisons between tofacitinib and either a placebo or biological therapy, no difference was found in the overall cancer risk (vs. placebo, RR = 1.04; 95% CI, 0.44–2.48; p = 0.95; vs. biological drugs, RR = 1.06; 95% CI, 0.86–1.31; p = 0.58). When tofacitinib was compared to tumor necrosis factor (TNF) inhibitors, the overall cancer RR was 1.40 (95% CI, 1.06–2.08; p = 0.02). Similarly, significant results were obtained for all cancers, except for non-melanoma skin cancer (RR = 1.47; 95% CI, 1.05–2.06; p = 0.03), and for this skin cancer alone (RR = 1.30; 95% CI, 0.22–5.83; p = 0.88). In conclusion, no difference in the overall cancer risk was found between tofacitinib and either a placebo or biological drugs, while a slightly higher risk was found in patients treated with tofacitinib than anti-TNF agents. Further studies are needed to better define the cancer risk of tofacitinib therapy.

Colonoscopy (CS) is the gold standard to assess postoperative recurrence (POR) in Crohn's disease (CD). However, CS is invasive and may be poorly tolerated by patients. The aim of this study was to prospectively assess the diagnostic accuracy of a noninvasive approach in detecting POR, using the endoscopic Rutgeerts' score (RS) as the reference standard.Consecutive patients with CD who underwent ileo-cecal resection were prospectively enrolled in 3 referral Italian centers. Patients underwent CS and bowel ultrasound within 1 year of surgery. Uni- and multivariable analyses were used to assess the correlation between noninvasive parameters and endoscopic recurrence, defined by a RS ≥2.Ninety-one patients were enrolled. Sixty patients (66%) experienced endoscopic POR. The multivariable analysis identified bowel wall thickness (BWT) per 1-mm increase (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.21-4.89; P = .012), the presence of mesenteric lymph nodes (OR, 15.63; 95% CI, 1.48-164.54; P = .022), and fecal calprotectin (FC) values ≥50 mcg/g (OR, 8.58; 95% CI, 2.45-29.99; P.001) as independent predictors for endoscopic recurrence. The presence of lymph nodes or the combination of BWT ≥3 mm and FC values ≥50 mcg/g correctly classified 56% and 75% of patients, with less than 5% of patients falsely classified as having endoscopic recurrence. Conversely, the combination of BWT3 mm and FC50 mcg/g correctly classified 74% of patients with only 4.5% of patients falsely classified as not having endoscopic recurrence.A noninvasive approach combining bowel ultrasound and FC can be used with confidence for detecting POR in patients with CD without the requirement for CS.

Background Endoscopic-post-operative-recurrence [ePOR] in Crohn’s disease [CD] after ileocecal resection [ICR] is a major concern. We aimed to evaluate the effectiveness of early prophylaxis with biologics and to compare anti-tumour necrosis factor [anti-TNF] therapy to vedolizumab [VDZ] and ustekinumab [UST] in a real-world setting. Methods A retrospective multicentre study of CD-adults after curative ICR on early prophylaxis was undertaken. ePOR was defined as a Rutgeerts score [RS] ≥ i2 or colonic-segmental-SES-CD ≥ 6. Multivariable logistic regression was used to evaluate risk factors, and inverse probability treatment weighting [IPTW] was applied to compare the effectiveness between agents. Results The study included 297 patients (53.9% males, age at diagnosis 24 years [19–32], age at ICR 34 years [26–43], 18.5% smokers, 27.6% biologic-naïve, 65.7% anti-TNF experienced, 28.6% two or more biologics and 17.2% previous surgery). Overall, 224, 39 and 34 patients received anti-TNF, VDZ or UST, respectively. Patients treated with VDZ and UST were more biologic experienced with higher rates of previous surgery. ePOR rates within 1 year were 41.8%. ePOR rates by treatment groups were: anti-TNF 40.2%, VDZ 33% and UST 61.8%. Risk factors for ePOR at 1 year were: past-infliximab (adjusted odds ratio [adj.OR] = 1.73 [95% confidence interval, CI: 1.01–2.97]), past-adalimumab [adj.OR = 2.32 [95% CI: 1.35-4.01] and surgical aspects. After IPTW, the risk of ePOR within 1 year of VDZ vs anti-TNF or UST vs anti-TNF was comparable (OR = 0.55 [95% CI: 0.25–1.19], OR = 1.86 [95% CI: 0.79–4.38]), respectively. Conclusion Prevention of ePOR within 1 year after surgery was successful in ~60% of patients. Patients treated with VDZ or UST consisted of a more refractory group. After controlling for confounders, no differences in ePOR risk were seen between anti-TNF prophylaxis and other groups.

The management of moderate to severe ulcerative colitis has undergone significant changes over the past 15 years due to the regulatory approval of several new drugs. In particular, following the approval of the first biological, i.e. infliximab, a number of further biological drugs, such as adalimumab, golimumab, vedolizumab and ustekinumab, and small molecules, such as tofacitinib, have been approved, thus enriching the therapeutic armamentarium for ulcerative colitis. Choice of therapy must take into consideration not only the need to induce and maintain disease remission according to the patient's profile, but also age, co-morbidities, and prior treatments. To guide these decisions, the Italian Group for the Study of Inflammatory Bowel Disease has developed clinical guidelines that supersede its earlier document from 2011. These new guidelines were developed following the GRADE methodology for rating the quality of the evidence and for determining the strength of the recommendations. This article presents the methodology and results, in the form of 20 statements with commentary on the use of the five biologics and tofacitinib for managing the intestinal manifestations of active ulcerative colitis and for maintaining remission. A separate technical review reports the analyses of the evidence upon which the present recommendations are based.

BACKGROUND AND AIMS: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators.METHODS: I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment.RESULTS: A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia.CONCLUSIONS: I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (EudraCT, Number: 2014-004728-23; ClinicalTrials.gov, Number: NCT02377258).

BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab for maintenance of remission in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, placebo-controlled, double-blind, phase 3 study (LAUREL) across 111 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. During open-label induction, participants received subcutaneous etrolizumab 105 mg once every 4 weeks. Participants who had clinical response at week 10 (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) proceeded into the double-blind maintenance phase and were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or matched placebo until week 62. Randomisation was stratified by baseline concomitant treatment with corticosteroids, treatment with immunosuppressants, baseline disease activity, and week 10 remission status. All participants and study site personnel were masked to treatment assignment. The primary endpoint was remission at week 62 (MCS ≤2, with individual subscores ≤1, and rectal bleeding subscore of 0) among patients with a clinical response at week 10, measured in the modified intention-to-treat population (all randomised patients who received at least one dose of study drug). This trial is registered with ClinicalTrials.gov, NCT02165215, and is now closed to recruitment. FINDINGS: Between Aug 12, 2014, and June 4, 2020, 658 patients were screened for eligibility and 359 were enrolled into the induction phase. 214 (60%) patients had a clinical response at week 10 and were randomly assigned to receive etrolizumab (n=108) or placebo (n=106) in the maintenance phase. 80 (74%) patients in the etrolizumab group and 42 (40%) in the placebo group completed the study through week 62. Four patients in the placebo group did not receive study treatment and were excluded from the analyses. At week 62, 32 (29·6%) of 108 patients in the etrolizumab group and 21 (20·6%) of 102 in the placebo group were in remission (adjusted treatment difference 7·7% [95% CI -4·2 to 19·2]; p=0·19). A greater proportion of patients reported one or more adverse events in the placebo group (82 [80%] of 102) than in the etrolizumab group (70 [65%] of 108); the most common adverse event in both groups was ulcerative colitis (16 [15%] patients in the etrolizumab group and 37 [36%] in the placebo group). Ten (9%) patients in the etrolizumab group and eight (8%) in the placebo group reported one or more serious adverse events. No deaths were reported in either treatment group. INTERPRETATION: No significant differences were observed between maintenance etrolizumab and placebo in the primary endpoint of remission at week 62 among patients who had a clinical response at week 10. Etrolizumab was well tolerated in this population and no new safety signals were identified. FUNDING: F Hoffmann-La Roche. ispartof: LANCET GASTROENTEROLOGY & HEPATOLOGY vol:7 issue:1 pages:28-37 ispartof: location:Netherlands status: published

Endoscopic evaluation with histological sampling is the gold standard for the diagnosis and follow-up of patients with inflammatory bowel disease (IBD), but in the past few years, gastrointestinal ultrasound (GIUS) has been gaining ground. Due to the transmural nature of inflammation in Crohn’s disease, GIUS has been mainly applied in this context. However, GIUS is now being reported to be accurate also for ulcerative colitis (UC). This review summarizes current knowledge on the use of GIUS in UC, with a focus on clinical practice. The review covers topics such as GIUS parameters, especially bowel wall thickness; the use of GIUS in assessing disease extent and in monitoring disease activity; GIUS indexes and scores; and the combination of GIUS with transperineal ultrasound for a better assessment of the rectum. With the always growing body of evidence supporting the accuracy of GIUS in UC, this diagnostic imaging modality can be expected to play a bigger role in disease flare evaluation, early treatment monitoring, and acute severe disease management.

Background and study aims Withdrawal time (WT) monitoring and full-spectrum endoscopy (FUSE) have been suggested to increase adenoma detection rate (ADR) due to more accurate evaluation of the hidden areas of the colon. We aimed to evaluate the efficacy of WT monitoring and FUSE on ADR. Patients and methods This was a prospective observational study involving consecutive outpatients, aged 18 to 85 years, undergoing colonoscopy with unselected indications. In phase 1, endoscopists performed 660 colonoscopies either with standard forward-viewing endoscope (SFVE) (n = 330) or with FUSE (n = 330). In this phase, WTs were measured without endoscopist awareness of being monitored. In phase 2, endoscopists were informed of being monitored and performed additional 660 colonoscopies either with SFVE (n = 330) or with FUSE (n = 330). Results WT was lower in phase 1 compared to phase 2 (SFVE: 269 ± 83 vs. 386 ± 60 sec, P Conclusions Unmonitored endoscopists have suboptimal WT, which increases when they are monitored. WT monitoring and use of FUSE are two reliable and alternative strategies to increase ADR.

Background and Aim Since the outbreak of COVID‐19, concerns have been raised as to whether inflammatory bowel disease (IBD) patients under biologic therapy may be more susceptible to the disease. This study aimed to determine the incidence and outcomes of COVID‐19 in a large cohort of IBD patients on biologic therapy. Methods This observational retrospective multicenter study collected data about COVID‐19 in IBD patients on biologic therapy in Italy, between February and May 2020. The main end‐points were (i) to assess both the cumulative incidence and clinical outcome of COVID‐19, according to different biologic agents and (ii) to compare them with the general population and a cohort IBD patients undergoing non‐biologic therapies. Results Among 1816 IBD patients, the cumulative incidence of COVID‐19 was 3.9 per 1000 (7/1816) with a 57% hospitalization rate and a 29% case‐fatality rate. The class of biologic agents was the only risk factor of developing COVID‐19 (P = 0.01). Non‐gut selective agents were associated with a lower incidence of COVID‐19 cases, related symptoms, and hospitalization (P

Background Few data exist regarding the long‐term effectiveness of golimumab in ulcerative colitis. No data have been reported on real‐world continuous clinical response. Objective This study aimed to describe the long‐term outcomes in a large cohort of patients on golimumab who had ulcerative colitis. Methods Consecutive patients with active ulcerative colitis, started on golimumab, were enrolled and prospectively followed up. The primary end point was to evaluate the long‐term persistence on golimumab therapy. Results A total of 173 patients with ulcerative colitis were studied. Of these, 79.2% were steroid dependent, and 46.3% were naïve to anti‐tumour necrosis factor alpha agents. The median duration of golimumab therapy was 52 weeks (range: 4–142 weeks). The cumulative probability of maintaining golimumab treatment was 47.3% and 22.5% at 54 and 108 weeks, respectively. Biological‐naïve status (odds ratio [OR] = 3.02, 95% confidence interval [CI]: 1.44–6.29; p = 0.003) and being able to discontinue steroids at Week 8 (OR = 3.32, 95% CI: 1.34–8.30; p = 0.010) and Week 14 (OR = 2.94, 95% CI: 1.08–8.02; p = 0.036) were associated with longer persistence on therapy. At Week 54, 65/124 (52.4%) postinduction responders were in continuous clinical response. A continuous clinical response was associated with a lower likelihood of golimumab discontinuation throughout the subsequent year of therapy (p

Background It is unclear whether patients with inflammatory bowel disease (IBD) are at increased risk of COVID-19. Objectives This observational study compared the prevalence of COVID-19 symptoms, diagnosis and hospitalization in IBD patients with a control population with non-inflammatory bowel disorders. Methods This multicentre study, included 2733 outpatients (1397 IBD patients and 1336 controls), from eight major gastrointestinal centres in Lombardy, Italy. Patients were invited to complete a web-based questionnaire regarding demographic, historical and clinical features over the previous 6 weeks. The prevalence of COVID-19 symptoms, diagnosis and hospitalization for COVID-19 was assessed. Results 1810 patients (64%) responded to the questionnaire (941 IBD patients and 869 controls). IBD patients were significantly younger and of male sex than controls. NSAID use and smoking were more frequent in controls. IBD patients were more likely treated with vitamin-D and vaccinated for influenza. Highly probable COVID-19 on the basis of symptoms and signs was less frequent in the IBD group (3.8% vs 6.3%; OR:0.45, 95%CI:0.28–0.75). IBD patients had a lower rate of nasopharyngeal swab-PCR confirmed diagnosis (0.2% vs 1.2%; OR:0.14, 95%CI:0.03–0.67). There was no difference in hospitalization between the groups (0.1% vs 0.6%; OR:0.14, 95%CI:0.02–1.17). Conclusion IBD patients do not have an increased risk of COVID-19 specific symptoms or more severe disease compared with a control group of gastroenterology patients.

Background Endoscopy plays a fundamental role in the management of patients with inflammatory bowel disease (IBD). The aim of this study was to prospectively evaluate the tolerability and efficacy of bowel preparation and colonoscopy in ulcerative colitis (UC) and Crohn’s disease (CD) patients compared to subjects participating in a colorectal cancer population screening program. Methods Consecutive enrolment of CD and UC patients and screening subjects (SS) undergoing colonoscopy. Bowel preparation was done by split dose of 2 L PEG-ELS + simethicone. We recorded endoscopic, clinical, and demographic features; cleanliness rating using the Boston Bowel Preparation Scale (BBPS); and sedation doses. Bowel-preparation tolerability, discomfort, and pain during colonoscopy were assessed using a Visual Analogue Scale from 0 to 100 mm. Results Sixty-three UC (mean age 49.9 ± 14.9 years), 63 CD (mean age 44.0 ± 14.0 years), and 63 SS (mean age 59.9 ± 6.3 years) patients were enrolled. Bowel preparation was similarly tolerated in UC, CD, and SS (P = 0.397). A complete colonoscopy was similarly performed in UC (59/63, 93.7%), CD (58/63, 92.1%), and SS (60/63, 95.2%) (P = 0.364). The BBPS did not show significant differences between UC (6.2 ± 1.6), CD (6.1 ± 1.3), and SS (6.2 ± 1.4) (P = 0.824). The need to increase sedation doses was significantly higher in CD (24/63, 38.1%) and UC (16/63, 25.4%) than in SS (4/63, 6.3%) (P < 0.0001). Conclusions Bowel preparation is equally tolerated and efficacious in IBD patients and in healthy SS. In IBD, higher sedation doses are needed to guarantee an equally tolerated colonoscopy.

Background During the COVID-19 outbreak in Italy, only fast-track endoscopic procedures have been performed; nevertheless, a significant drop in their number has been reported. We evaluated whether the pandemic has impacted the appropriateness and diagnostic yield of fast-track endoscopic procedures compared with those performed in 2019. Methods This retrospective study involved endoscopy services in Northern Italy. We compared data regarding endoscopic procedures performed in March and April 2020 with those performed during the same period in 2019. Results In 2020, there was a 53.6 % reduction in the number of fast-track endoscopic procedures compared with 2019. Patients undergoing endoscopy in 2020 were younger than in 2019. Both appropriate referral and diagnostic yield increased in 2020 for both upper and lower endoscopy. A higher rate of cancer was diagnosed in 2020 by upper endoscopy (3.6 % vs. 6.6 %; P = 0.04). Conclusions The high level of inappropriate endoscopy referrals registered in 2019 significantly improved during the COVID-19 outbreak of 2020, with an increase in the diagnostic yield.

The current coronavirus pandemic is an ongoing global health crisis due to covid-19, caused by severe acute respiratory syndrome coronavirus 2. Although covid-19 leads to little or mild flu-like symptoms in the majority of affected patients, the disease may cause severe, frequently lethal complications such as progressive pneumonia, acute respiratory distress syndrome and organ failure driven by hyperinflammation and a cytokine storm syndrome. This situation causes various major challenges for gastroenterology. In the context of IBD, several key questions arise. For instance, it is an important question to understand whether patients with IBD (eg, due to intestinal ACE2 expression) might be particularly susceptible to covid-19 and the cytokine release syndrome associated with lung injury and fatal outcomes. Another highly relevant question is how to deal with immunosuppression and immunomodulation during the current pandemic in patients with IBD and whether immunosuppression affects the progress of covid-19. Here, the current understanding of the pathophysiology of covid-19 is reviewed with special reference to immune cell activation. Moreover, the potential implications of these new insights for immunomodulation and biological therapy in IBD are discussed.

Background and aims Restarting activity in Endoscopic Departments (ED) after COVID-19 lockdown raises critical issues. This survey investigates strategies and uncertainties on resumption of elective activity. Methods Directors of 55 EDs in Northern Italy received a questionnaire focusing on the impact of pandemic on activity and organization and on the resources available at re-opening. A section was devoted to gather forecasts and proposals on the return path to normality. Results All centres had reduced their activities of at least 50% of the pre-COVID-19 period. A rate of endoscopists (13.6%), nurses (25.2%), and health assistants (14%) were not available since infected, or relocated to other departments. One third of endoscopic rooms were converted to COVID-19 care. Two third had the waiting or the recovery areas too small for distancing. A dedicated pathway for infected patients could not be guaranteed in 20% of EDs. Only one third of EDs judged realistic to completely restore a pre-crisis workload by the next months. Optimizing appropriateness of procedures, closer interaction with GPs and triaging patients with telemedicine were the proposals to re-open EDs. Conclusions The critical issues while re-opening EDs calls for reducing the workload in the endoscopy units through appropriate rescheduling of procedures. Funding None

ObjectivesCOVID-19 has rapidly become a major health emergency worldwide. Patients with IBD are at increased risk of infection, especially when they have active disease and are taking immunosuppressive therapy. The characteristics and outcomes of COVID-19 in patients with IBD remain unclear.DesignThis Italian prospective observational cohort study enrolled consecutive patients with an established IBD diagnosis and confirmed COVID-19. Data regarding age, sex, IBD (type, treatments and clinical activity), other comorbidities (Charlson Comorbidity Index (CCI)), signs and symptoms of COVID-19 and therapies were compared with COVID-19 outcomes (pneumonia, hospitalisation, respiratory therapy and death).ResultsBetween 11 and 29 March 2020, 79 patients with IBD with COVID-19 were enrolled at 24 IBD referral units. Thirty-six patients had COVID-19-related pneumonia (46%), 22 (28%) were hospitalised, 7 (9%) required non-mechanical ventilation, 9 (11%) required continuous positive airway pressure therapy, 2 (3%) had endotracheal intubation and 6 (8%) died. Four patients (6%) were diagnosed with COVID-19 while they were being hospitalised for a severe flare of IBD. Age over 65 years (p=0.03), UC diagnosis (p=0.03), IBD activity (p=0.003) and a CCI score >1 (p=0.04) were significantly associated with COVID-19 pneumonia, whereas concomitant IBD treatments were not. Age over 65 years (p=0.002), active IBD (p=0.02) and higher CCI score were significantly associated with COVID-19-related death.ConclusionsActive IBD, old age and comorbidities were associated with a negative COVID-19 outcome, whereas IBD treatments were not. Preventing acute IBD flares may avoid fatal COVID-19 in patients with IBD. Further research is needed.

BACKGROUND AND AIMS: Restructuring activities have been necessary during the lockdown phase of the coronavirus disease 2019 (COVID-19) pandemic. Few data are available on the post-lockdown phase in terms of health-care procedures in inflammatory bowel disease (IBD) care, and no data are available specifically from IBD units. We aimed to investigate how IBD management was restructured during the lockdown phase, the impact of the restructuring on standards of care and how Italian IBD units have managed post-lockdown activities. METHODS: A web-based online survey was conducted in two phases (April and June 2020) among the Italian Group for IBD affiliated units within the entire country. We investigated preventive measures, the possibility of continuing scheduled visits/procedures/therapies because of COVID-19 and how units resumed activities in the post-lockdown phase. RESULTS: Forty-two referral centres participated from all over Italy. During the COVID-19 lockdown, 36% of first visits and 7% of follow-up visits were regularly done, while >70% of follow-up scheduled visits and 5% of first visits were done virtually. About 25% of scheduled endoscopies and bowel ultrasound scans were done. More than 80% of biological therapies were done as scheduled. Compared to the pre-lockdown situation, 95% of centres modified management of outpatient activity, 93% of endoscopies, 59% of gastrointestinal ultrasounds and 33% of biological therapies. Resumption of activities after the lockdown phase may take three to six months to normalize. Virtual clinics, implementation of IBD pathways and facilities seem to be the main factors to improve care in the future. CONCLUSION: Italian IBD unit restructuring allowed quality standards of care during the COVID-19 pandemic to be maintained. A return to normal appears to be feasible and achievable relatively quickly. Some approaches, such as virtual clinics and identified IBD pathways, represent a valid starting point to improve IBD care in the post-COVID-19 era.

Background Ustekinumab (UST) is increasingly used in Italy for the treatment of refractory Crohn’s disease (CD), however very few data concerning real-life experience has been reported. Therefore, the aim of this study was to assess the long-term effectiveness of UST in refractory CD patients treated in a large Italian cohort. Methods A retrospective study was conducted in 5 Italian tertiary centers. All adult CD patients who started UST because of anti-tumor necrosis factor (TNF) failure were included. The co-primary outcomes were steroid-free clinical remission (defined as Harvey Bradshaw Index, HBI ≤4) at weeks 26 and 52. Secondary outcomes were changes in HBI score, changes in C-reactive protein (CRP) values, normalization of CRP (≤0.5 mg/dl) at weeks 8, 26, and 52, and adverse events. Categorical variables were expressed as frequency and percentage. Unpaired t-test was used to compare variables. A p-value Results Between Nov 2018 and Feb 2020,140 patients (51.4% male; median age 45.0 years, IQR 36.3-54.0; median disease duration 16.0 years, IQR 8.0-22.0) were included. The majority of patients had ileocolonic disease (L1, 38.6%; L2, 11.4%; L3, 50.0%) and an inflammatory phenotype (B1, 50.7%; B2, 31.0%; B3, 18.3%). All patients had previously been exposed to at least one anti-TNF agent, 27.1% to 2 anti-TNF agents, and 20.0% to vedolizumab . At inclusion 15.7% of patients received corticosteroids and 8.6% immunomodulators. All patients received an intravenous dose of 6 mg/kg, followed by subcutaneous administration of 90 mg every 8 (90%) or 12 weeks (10%) according to clinical judgment. The proportion of patients achieving steroid-free clinical remission was 61.0% and 64.2% at weeks 26 and 52 respectively. A significant decrease in the mean HBI was reported from baseline to week 8 (6.8 ± 3.6 vs 4.5 ± 3.1; p Conclusion To our knowledge this is one of the largest Italian cohort followed up to 1 year, and the results confirm that UST is an effective and safe treatment in refractory CD patients.

Background Prevention of postoperative recurrence is a critical goal in Crohn’s disease (CD) management. Currently, postsurgical CD management and treatment are based on endoscopic monitoring performed within the first year after surgery. However, colonoscopy (CS) is an invasive and expensive procedure, unpleasant to patients. A non-invasive and patient friendly approach is required. Methods Consecutive CD patients who underwent ileo-cecal resection from July 2017 to January 2020 were prospectively enrolled in three Italian Centers and performed CS and bowel ultrasound (US) after six months from the surgery, in a blinded fashion. The patients also underwent complete clinical assessment and blood and stool samples were obtained for C-reactive protein (CRP), and fecal calprotectin (FC) measurements. The disease was considered clinically active if the Harvey–Bradshaw Index (HBI) was higher than 4. Uni- and multivariable analyses were used to assess the correlation between non-invasive parameters, including bowel US findings and FC values and endoscopic recurrence, defined by a Rutgeerts’s score (RS) > 2. Sensitivity, specificity, accuracy, PPV and NPV of bowel US parameters alone and in combination with FC in assessing endoscopic recurrence were calculated. Results Seventy patients were enrolled, 45 patients (64%) had an endoscopic recurrence (RS > 2) at 6 months. Thirteen out of 45 (29%) were symptomatic (HBI > 4). Bowel wall thickness (BWT), bowel wall flow (BWF, presence of vascular signals at color Doppler), the presence of mesenteric hypertrophy, the presence of limph-nodes and FC values significantly correlated with the endoscopic recurrence (p < 0.005). Independent predictors for endoscopic recurrence were BWT (for 1-mm increase: OR 2.63; 95% CI 1.136.12; p= 0.024), presence of lymph-nodes (OR 23.24; 95% CI 1.85291.15; p= 0.014) and FC > 50 µg/g (OR 11.86; 95% CI 2.60–54.09; p= 0.001). Sensitivity, specificity, accuracy, PPV and NPV of bowel US and/or FC are showed in Table 1. Table 1: Diagnostic accuracy of Bowel US and/or FC compared to CS in assessing endoscopic activity (CI 95%): per-patient analysis Conclusion Combined use of bowel US and FC is accurate in assessing endoscopic recurrence at 6 months in CD patients and represent a valid alternative to endoscopic assessment after surgery

Background The appropriate maintenance treatment for patients with acute severe ulcerative colitis (ASUC) responsive to intravenous steroids (IVS) is still a matter of debate. Although major Guidelines consider thiopurine maintenance an option in this setting, the long-term benefit of early immunomodulator (IMMs) initiation is not well established. The aim of our study was to explore the long-term outcome of patients with ASUC responsive to IVS who received different maintenance strategies Methods In a multicenter retrospective study, all patients with ASUC hospitalized between January 2005 and December 2017 in 14 Italian IBD referral centres were reviewed. Thiopurine and biologic-naïve patients experiencing their first acute severe attack and who responded to IVS were included in the study. Maintenance treatment was prescribed by attending physicians according to their clinical judgment. The main outcomes were recurrent flares requiring escalation of therapy, new hospitalization, and long-term colectomy rate. The Kaplan-Meier survival method was used to estimate the cumulative probability of a course without the main outcomes. Differences between curves were tested using the log-rank test. A propensity score matching analysis was performed to establish comparable groups of patients who received different maintenance treatment Results Overall 372 patients were reviewed. Of these, 141 met the inclusion criteria (males 61.7%, median age 34.5 (IQR 23–50). After response to IVS, 82 patients (58.1%) received maintenance treatment with aminosalicylates, 42 (29.8%) received IMMs and 17 (12.1%) were maintained with scheduled infliximab (IFX) + thiopurines. After a median follow-up of 48 (IQR 25–90) months, 94 patients (68.8%) experienced a flare requiring escalation of therapy, 51 (36.1%) required new hospitalization and 18 (12.8%) underwent colectomy. After 12, 36 and 60 months after the acute attack, the cumulative probability of a course without escalation of therapy was 59.6%, 33.3% and 23.1%; the cumulative probability of a hospitalization-free course was 83.9%, 67.4% and 59.5%; the cumulative probability of a colectomy-free course was 96.3%, 90.2%, and 88.9%. No differences were observed between patients receiving aminosalicylates, IMMs or IFX as maintenance treatment (log-rank test: p= 0.39; p = 0.41; p = 0.11 respectively). After a propensity score matching analysis, no significant difference in main outcomes was observed between patients maintained with aminosalicylates or IMMs/IFX Conclusion IMM-naïve ASUC patients responsive IVS remain at risk of relapse requiring escalation of therapy. Early IMMs introduction after the acute attack did not reduce the risk of escalation of therapy, hospitalization or colectomy

Background IBD patients are intended to undergo several times colonoscopy during their lifespan. Adequate bowel preparation and sedation greatly contribute to high-quality colonoscopy and are even more important in this setting. However, few and low-quality studies addressed these issues. Aims: to prospectively evaluate the tolerability of bowel preparation and colonoscopy in ulcerative colitis (UC) and Crohn’s disease (CD) patients compared with subjects participating in a colorectal cancer population screening programme. Methods we consecutively enrolled CD and UC patients and screening subjects (SS) undergoing colonoscopy between August 2017 and August 2019. Bowel preparation was done by macrogol 4.000 + simethicone + sodium-sulphate-anhydrous. We recorded endoscopic, clinical and demographic features; quality of cleansing by Boston Bowel Preparation Scale (BBPS; from 0 the worst to 9 the best); sedation dose and need to increase the initial doses of midazolam (3.0 mg) and fentanyl (0.05 mg). Tolerability of bowel preparation, discomfort and pain during colonoscopy were assessed by Visual Analogue Scale (VAS) from 0 to 100 mm. Results 65 UC (26 women, mean age 50.6 ± 15.4 years), 65 CD (29 women, mean age 44.7 ± 3.9) and 94 SS (47 women, mean age 61.9 ± 6.9) enrolled. Bowel preparation was similarly tolerated in UC (70.3 ± 17.7 mm), CD (73.1 ± 12.7 mm) and SS (73.2 ± 12.6 mm) (p = 0.397). Complete colonoscopy was similarly done in UC (61/65, 93.8%), CD (60/65, 92.3%) and SS (91/94, 96.8%) (p = 0.364). BBPS did not show significant differences between UC (6.5 ± 1.0), CD (6.4 ± 1.1) and SS (6.4 ± 1.0) (p = 0.824). The need to increase sedation doses was significantly higher in CD (26/65, 40.0%) and UC (16/65, 24.6%) than in SS (4/94, 4.3%) (p < 0.0001). The mean increases in midazolam and fentanyl doses were significantly higher in CD (0.446 ± 0.660 mg and 0.009 ± 0.019 mg, respectively) and UC (0.300 ± 0.620 and 0.008 ± 0.018 mg) than in SS (0.042 ± 0.250 mg and 0.001 ± 0.007 mg) (p < p < 0.0001 in both cases). Discomfort and pain during colonoscopy were similar in UC (35.0 ± 23.0 mm and 27.6 ± 24.6 mm, respectively), CD (37.5 ± 22.2 mm and 28.8 ± 22.5 mm) and SS 33.7 ± 18.7 and 26.9 ± 19.8 mm) (p = 0.530 and p = 0.866, respectively). Conclusion in IBD patients, higher sedation doses are needed in order to warrant a tolerated colonoscopy. Bowel preparation is equally tolerated and efficacious in IBD patients and in screening subjects.

The first infliximab biosimilar for the treatment of inflammatory bowel disease (IBD) was introduced in 2013, and today eight anti-TNF alpha biosimilars (three for infliximab and five for adalimumab) have been approved and licensed by the European Medicines Agency. Biosimilars present great potential in terms of cost saving and possible consequential reinvestment in the health care system. The increasing knowledge about the process of biosimilar development and use in IBD and the publication of many prospective clinical studies and real-life clinical experiences have progressively changed the point of view of IBD physicians. In the present position paper, the Italian Group for the Study of Inflammatory Bowel Disease present and discuss their updated statements and positions on this topic, with emphasis on the concepts of biosimilarity and extrapolation across indications, safety and immunogenicity, interchangeability and switching, automatic substitution, and, finally, patient education about biosimilars.

BACKGROUND Disease phenotype and outcome of late-onset Crohn's disease are still poorly defined. METHODS In this Italian nationwide multicentre retrospective study, patients diagnosed ≥65 years (late-onset) were compared with young adult-onset with 16-39 years and adult-onset Crohn's disease 40-64 years. Data were collected for 3 years following diagnosis. RESULTS A total of 631 patients (late-onset 153, adult-onset 161, young adult-onset 317) were included. Colonic disease was more frequent in late-onset (P < 0005), stenosing behaviour was more frequent than in adult-onset (P < 0003), but fistulising disease was uncommon. Surgery rates were not different between the three age groups. Systemic steroids were prescribed more frequently in young adult-onset in the first year, but low bioavailability steroids were used more frequently in late-onset in the first 2 years after diagnosis (P < 0.036, P < 0.041, respectively). The use of immunomodulators and anti-TNF's even in patients with more complicated disease, that is, B2 or B3 behaviour (Montreal classification), remained significantly inferior (P < 0.0001) in late-onset compared to young adult-onset. Age at diagnosis, Charlson comorbidity index, and steroid used in the first year were negatively associated with the use of immunomodulators and biologics. Comorbidities, related medications and hospitalizations were more frequent in late-onset. Polypharmacy was present in 56% of elderly Crohn's disease patients. CONCLUSION Thirty-two percent of late-onset Crohn's disease presented with complicated disease behaviour. Despite a comparable use of steroids and surgery, immunomodulators and biologics were used in a small number of patients.

BACKGROUND We report a prospective, nationwide cohort evaluating the safety and effectiveness of CT-P13. METHODS A structured database was used to record serious adverse events (SAEs), clinical remission/response, inflammatory biomarkers (CRP and calprotectin), and endoscopic findings. RESULTS Eight hundred ten patients with inflammatory bowel disease (IBD) (452 Crohn's disease [CD]) were enrolled. Four hundred fifty-nine patients were naive to anti-TNFα (group A), 196 had a previous exposure (group B), and the remaining 155 were switched to CT-P13 (group C). All patients were included in the safety evaluation with a mean follow-up of 345 ± 215 days and a total number of 6501 infusions. One hundred fifty-four SAEs were reported (19%), leading to cessation of the biosimilar in 103 subjects (12.7%). Infusion reactions were 71, leading to cessation of the biosimilar in 53 subjects (6.5%), being significantly more frequent in patients pre-exposed to anti-TNFα (P = 0.017). The efficacy of therapy was calculated in 754 IBD patients, with a mean follow-up of 329 ± 202 days. Forty-eight patients had a primary failure (6.4%), and 188 (25.6%) lost response during follow-up. Six hundred twenty-eight (364 CD) and 360 IBD patients (222 CD) completed the follow-up at 6 and 12 months, respectively. At 12 months, patients without loss of response were 71%, 64%. and 82% in groups A, B, and C, respectively (log rank P = 0.01). Clinical/endoscopic scores and inflammatory biomarkers dropped significantly in CD and UC patients (P = 0.01 and P < 0.0001) compared with baseline. CONCLUSIONS In this large prospective cohort, no further signals of difference in safety and effectiveness of CT-P13 in IBD has been observed.

Background: Late-onset UC represents an important issue for the near future, but its outcomes and relative therapeutic strategies are yet poorly studied. Aim: To better define the natural history of late-onset ulcerative colitis. Methods: In a multicenter retrospective study, we investigated the disease presentation and course in the first 3 years in 1091 UC patients divided into 3 age-groups: diagnosis >65 years, 40-64 years, and

Background: Tissue organisation field theory explains that cancer starts as a result of an alteration in supporting tissue and inflammatory cells. The immunoglobulins (Igs) detected in colorectal adenocarcinomas come from the loss of integrity of resident μ chain-producing cells. Nearly half of the contact residues of Igs are aromatic and highly reactive. In the same way, the vast majority of cell surface proteins in the extra-cellular matrix contain a number of different domains or modules. The (Arg-Gly-Asp) RGD receptor domain of fibronectin constitutes cell adhesion receptors for cell-matrix adhesion and for bidirectional signaling across the membrane. Highly homologous oligopeptides emulate and compete with matrix adhesive proteins: Streptavidin binds to cells via the (Arg-Tyr- Asp) RYD mimetic RGD peptide. Furthermore, tyrosine-tryptophan-threonine-aspartic acid (YWTD) domains, physiologically binds laminin and seven different endocytic receptors contain 1-8 YWTD beta-propeller domains.Objective: The primary aim of this study was to evaluate the in situ presence and distribution of μ chains in 46 colorectal tumors of different histological grades using fluoresceinate goat anti-human μ chains. The secondary aim was to evaluate the cell and stromal interactions of the fluoresceinate YWTD, RGD antigens and streptavidin in sequential biopsy specimens of the same samples.Results: The detection of μ chains was low in the adenomas and high in the adenocarcinomas. Two morphological types of B cells differently associated with tissue integrity. Only stromal μ chain-producing cells strongly bound YWTD, RGD and streptavidin.Conclusion: In colorectal tumors, RGD-mimicking site peptides mainly compete with fibronectin/immunoglobulin binding. The presence of μ chain/YWTD interactions shows that sequences richer in aromatic residues should be considered.