Abstract Background Inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis (UC), are chronic and immune-mediated diseases with a relapsing-remitting trend. The overall incidence of these diseases is increasing. However, it is estimated that more than one third of patients experienced symptoms for more than one year before diagnosis. Delay in IBD diagnosis has several clinical, therapeutic and economic implications. Early diagnosis and proper treatment are the cornerstones for improving the standard of care for these patients. This study aims to evaluate the diagnostic delay (DD) in patients with IBD and to analyze the clinical burden of the delay in IBD diagnosis in patients treated with biological drugs. Methods An observational and retrospective study was performed in IBD patients, regularly followed in four IBD Units. Data regarding delay in IBD diagnosis were assessed through a questionnaire evaluating the disease course. Moreover, data about biologics dispensation were obtained from the medical records in the period 2020-2022 Results 344 IBD patients were enrolled (UC 228, CD 116, M 198, F 146). Median age at diagnosis was 42 years (IQR 9-82); Median DD was 12 months (IQR: 6-24). No significant difference was found in median DD between UC [12 months (IQR: 4.5-12.0)] and CD patients [12 months (IQR: 12-48)]. However, the proportion of patients with a DD >24 months was significantly (p=0.007) higher in CD (41/110 = 37,3%) than in UC patients (20/220=9%). After a median disease duration of 10 years (IQR: 4-17), overall, 164 patients (49.7%) were exposed to one biologic agent, 105 patients (31.8%) were exposed to two biologic agents, 61 (18.5%) to three or more biologic agents. 18,5% of patients (61/330) underwent surgery. The statistical analysis showed that DD >24 months was not statistically significant associated with history of ≥ 2 biological drugs (p=0.51). Conversely, there was association with surgical treatment (p=0.004). Conclusion The diagnostic delay in IBD represents a challenge with clinical and, therapeutic impact. It’s crucial to cooperate with general practitioner and gastroenterologists not dedicated to IBD in order to reduce the diagnostic delay and guarantee an effective, appropriate and early treatment that will improve the patients’ quality of life and meanwhile reduce the health care system costs.

BackgroundUstekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC) but with limited real-world data. Therefore, we evaluated the effectiveness and safety of UST in patients with UC in a real-world setting.Research design and methodsThis is a multicenter, retrospective, observational cohort study. The primary endpoints were the clinical remission rate (partial Mayo score, PMS, <= 1) and the safety of UST. Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and fecal calprotectin (FC) reduction at week 24.ResultsWe included 256 consecutive patients with UC (M/F 139/117, median age 52). The clinical remission and clinical response rates at eight weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 (p = 0.0004) and 24 (p = 0.038). At eight weeks, patients naive or with one previous biologic treatment showed higher remission (p = 0.002) and clinical response rates (p = 0.018) than patients previously treated with >= 2. Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy.ConclusionThis real-world study shows that UST effectively and safely treats patients with UC.

Background: Ustekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist approved for the treatment of Crohn’s disease (CD). Only limited real-life data on the long-term outcomes of CD patients treated with UST are available. This study assessed UST’s long-term effectiveness and safety in a large population-based cohort of moderate to severe CD patients. Methods: This was a multicenter, retrospective, observational cohort study that included both naïve and biologic-experienced patients treated with UST who achieved clinical remission or clinical response after at least one year of treatment. Clinical activity was scored according to the Harvey–Bradshaw Index (HBI). The primary endpoints were the maintenance or achievement of clinical remission after a further 12-month period of treatment, defined as an HBI of ≤5, and safety. Other endpoints included steroid-free remission, mucosal healing (MH), steroid discontinuation, and the need for treatment optimization during the follow-up. Results: Out of 562 CD patients, after an overall 24-month follow-up, clinical remission was present in 450 (80.0%) patients, and at 12 months, clinical remission was observed in 417/437 (95.4%) patients; 33/125 (26.4%) showed clinical response at 12 months (p = 0.000). A total of 38/103 (36.9%) patients achieved MH. Only 2.1% (12/562), 3% (17/562), and 1.1% (6/562) of patients required surgery, optimization, and re-induction, respectively. Adverse events occurred in eight patients (1.42%). According to a multivariate analysis, the only predictor of long-term remission was the presence of remission at the 12-month follow-up (p = 0.000). Conclusions: Long-term treatment with UST presents good efficacy and safety profiles in CD patients, especially for patients who achieve remission after one year.

Background/Aims: Endoscopic stenting for stricturing Crohn's disease (CD) is an emerging treatment that achieves more persistent dilatation of the stricture over time than endoscopic balloon dilatation (EBD). We aimed to explore the efficacy and safety of stenting for the treatment of CD strictures.Methods: A systematic electronic literature search was performed (PROSPERO; no. CRD42022308033). The primary outcomes were technical success, efficacy, complication rate, and the need for further interventions due to reobstruction. The outcomes of partially covered self-expanding metal stents (PCSEMS) with scheduled retrieval after seven days were also analyzed.Results: Eleven eligible studies were included in the review. Overall, 173 patients with CD were included in this study. Mean percentage of technical success was 95% (range, 80%–100%), short-term efficacy was 100% in all studies, and long-term efficacy was 56% (range, 25%–90%). In patients with a scheduled PCSEMS retrieval, the long-term efficacy was 76% (range, 59%–90%), the mean complication rate was 35% (range, 15%–57%), and the major complication rate was 11% (range, 0%–29%).Conclusions: Endoscopic stenting with scheduled PCSEMS retrieval may be considered a feasible second-line treatment for short CD strictures to postpone surgery. However, larger head-to-head prospective studies are needed to understand the role of stenting as an alternative or additional treatment to EBD in CD.

BackgroundData regarding the real-world (RW) use of tofacitinib (TOF) in patients with ulcerative colitis (UC) are limited. We aimed to investigate TOF's RW efficacy and safety in Italian UC patients.Research design and methodsA retrospective assessment of clinical and endoscopic activity was performed according to the Mayo score. The primary endpoints were to evaluate the effectiveness and safety of TOF.ResultsWe enrolled 166 patients with a median follow-up of 24 (IQR 8-36) weeks. Clinical remission was achieved in 61/166 (36.7%) and 75/166 (45.2%) patients at 8-week and 24-week follow-ups, respectively. The optimization was requested in 27 (16.3%) patients. Clinical remission was achieved more frequently when TOF was used as a first/second line rather than a third/fourth line treatment (p = 0.007). Mucosal healing was reported in 46% of patients at the median follow-up time. Colectomy occurred in 8 (4.8%) patients. Adverse events occurred in 12 (5.4%) patients and severe in 3 (1.8%). One case of simple Herpes Zoster and one of renal vein thrombosis were recorded.ConclusionsOur RW data confirm that TOF is effective and safe in UC patients. It performs remarkably better when used as the first/second line of treatment.

Background Adalimumab (ADA) biosimilars have entered the therapeutic armamentarium of inflammatory bowel disease (IBD), allowing for the treatment of a greater number of patients for their reduced cost than the originator. However, comparative data on the efficacy and safety of the various ADA biosimilars remains scarce. We compare the efficacy and safety of ADA biosimilars SB5, APB501, GP2017, and MSB11022 in treating IBD outpatients in a real-life Italian setting. Methods A retrospective analysis was performed on consecutive IBD outpatients with complete clinical, laboratory, and endoscopic data. Clinical activity was measured using the Mayo score in ulcerative colitis (UC) and the Harvey-Bradshaw Index in Crohn's disease (CD). The primary endpoints were the following: (1) induction of remission in patients new to biologics and patients new to ADA but previously exposed to other anti-tumor necrosis factor agents or other biologics; (2) maintenance of remission in patients switched from the ADA originator to an ADA biosimilar; and (3) safety of various biosimilars. Results A total of 533 patients were enrolled according to the inclusion criteria: 162 patients with UC and 371 patients with CD. Clinical remission was obtained in 79.6% of patients new to biologics and 59.2% of patients new to ADA but not to other biologics; clinical remission was maintained in 81.0% of patients switched from the originator, and adverse events were recorded in 6.7% of patients. There was no significant difference between the 4 ADA biosimilars for each predetermined endpoint. Conclusions Adalimumab biosimilars are effective and safe in IBD treatment, both in new patients and in patients switched from the ADA originator. No difference in efficacy and safety was found between ADA biosimilars. Lay Summary We treated 533 IBD patients with adalimumab (ADA) biosimilars SB5, APB501, GP2017, and MSB11022. No differences between these 4 ADA biosimilars were found for reaching remission in naive patients, maintaining remission for nonmedical switching, clinical response, steroid-free remission, surgery rate, mucosal healing, or safety.

Abstract Background Current data about long-term use of vedolizumab (VDZ) in ulcerative colitis (UC) versus Crohn’s disease (CD) patients are limited. We aimed to assess whether there are differences in term of long-term efficacy and safety of VDZ in UC vs. CD patients. Methods Clinical activity was scored according to the Mayo score in UC and to the Harvey-Bradshaw Index (HBI) in CD. The primary endpoints were the achievement of clinical remission within 6 month of treatment, maintenance of clinical remission during a long follow-up, and safety. Secondary endpoints were clinical response to treatment, achievement of mucosal healing (MH), steroid discontinuation, and treatment optimization during the follow-up. Results The study group consisted of 729 patients (475 patients with UC and 254 CD patients with CD) with a median follow-up of 18 (interquartile range 6-36) months. Clinical remission at the 6th month of treatment was achieved in 488 (66.9%) patients, higher in CD patients (74.4 vs. 62.9, p<0.000) while, at the maximal follow-up, it was achieved and maintained in 81.5% of patients (UC vs. CD, p=0.667). At uni- and multivariate analysis, reaching clinical remission at the 6th month of treatment (p=0.001) and being naïve to biologics were significantly associated with longer clinical remission (p<0.0001). Long-term follow up clinical response was significantly higher in UC vs. CD (p=0.023) and surgery occurred more frequently in CD (p=0.04), while no difference were found between UC and CD about the other secondary endpoints Conclusion Overall, no significant differences were found about the long-term use of VDZ in UC vs. CD. However, we identified some parameters the can help the physician to predict the long-term efficacy of this drug.

ABSTRACT Background Vedolizumab (VDZ) can be used to treat refractory ulcerative colitis (UC) and Crohn’s disease (CD). We assessed whether there are differences in treating UC vs CD with VDZ. Research design and methods Mayo score in UC and the Harvey-Bradshaw Index (HBI) in CD scored the clinical activity. Achievement and maintenance of clinical remission during the follow-up, and safety were the primary endpoints. Results 729 patients (475 with UC and 254 with CD), median follow-up of 18 (IQR 6-36) months, were enrolled. Clinical remission at the 6th month of treatment was achieved in 488 (66.9%) patients (74.4% in CD vs 62.9% in UC, p<0.002) while, during the follow-up, no difference was found (81.5% in the UC group and 81.5% pts in the CD group; p=0.537). The clinical remission at the 6th month of treatment (p=0.001) and being naïve to biologics (p<0.0001) were significantly associated with prolonged clinical remission. The clinical response was significantly higher in UC (90.1%) vs CD (84.3%) (p=0.023), and surgery occurred more frequently in CD (1.9% in UC vs 5.1% in CD, p=0.016). Conclusion We found differences when using VDZ in UC vs CD in real life. These parameters can help the physician predict this drug’s longterm efficacy.

Abstract Background Inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis (UC), are chronic and immune-mediated diseases with a relapsing-remitting trend. The overall incidence of these diseases is increasing. However, it is estimated that more than one third of patients experienced symptoms for more than one year before diagnosis. Delay in IBD diagnosis has several clinical, therapeutic and economic implications. Early diagnosis and proper treatment are the cornerstones for improving the standard of care for these patients. This study aims to evaluate the diagnostic delay (DD) in patients with IBD and to analyze the clinical burden of the delay in IBD diagnosis in patients treated with biological drugs. Methods An observational and retrospective study was performed in IBD patients, regularly followed in four IBD Units. Data regarding delay in IBD diagnosis were assessed through a questionnaire evaluating the disease course. Moreover, data about biologics dispensation were obtained from the medical records in the period 2020-2022 Results 135 IBD patients were enrolled (UC 72, CD 63, M 80, F 55). Median age at diagnosis was 32 years (IQR 22-45); 7% of patients were ≤ 16 years old at diagnosis. Median age on erollement was 47 ( IQR 4-59) Median DD was 12 months (IQR: 6-24). No significant difference was found in median DD between UC [12 months (IQR: 4.5-12.0)] and CD patients [12 months (IQR: 12-48)]. However, the proportion of patients with a DD >24 months was significantly (p=0.007) higher in CD (21/63 = 33%) than in UC patients (10/72=13%). After a median disease duration of 10 years (IQR: 4-17), overall, 67 patients (49.7%) were exposed to one biologic agent, 43 patients (31.8%) were exposed to two biologic agents, 25 (18.5%) to three or more biologic agents. 23% of patients (31/135) underwent surgery. The statistical analysis showed that DD >24 months was not statistically significant associated with history of ≥ 2 biological drugs (p=0.51). Conversely, there was association with surgical treatment (p=0.004). Conclusion The diagnostic delay in IBD represents a challenge with clinical and, therapeutic impact. It’s crucial to cooperate with general practitioner and gastroenterologists not dedicated to IBD in order to reduce the diagnostic delay and guarantee an effective, appropriate and early treatment that will improve the patients’ quality of life and meanwhile reduce the health care system costs.

BACKGROUND & AIMS:Artificial intelligence (AI) may detect colorectal polyps that have been missed due to perceptual pitfalls. By reducing such miss rate, AI may increase the detection of colorectal neoplasia leading to a higher degree of colorectal cancer (CRC) prevention. METHODS:Patients undergoing CRC screening or surveillance were enrolled in 8 centers (Italy, UK, US), and randomized (1:1) to undergo 2 same-day, back-to-back colonoscopies with or without AI (deep learning computer aided diagnosis endoscopy) in 2 different arms, namely AI followed by colonoscopy without AI or vice-versa. Adenoma miss rate (AMR) was calculated as the number of histologically verified lesions detected at second colonoscopy divided by the total number of lesions detected at first and second colonoscopy. Mean number of lesions detected in the second colonoscopy and proportion of false negative subjects (no lesion at first colonoscopy and at least 1 at second) were calculated. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted by endoscopist, age, sex, and indication for colonoscopy. Adverse events were also measured. RESULTS:A total of 230 subjects (116 AI first, 114 standard colonoscopy first) were included in the study analysis. AMR was 15.5% (38 of 246) and 32.4% (80 of 247) in the arm with AI and non-AI colonoscopy first, respectively (adjusted OR, 0.38; 95% CI, 0.23-0.62). In detail, AMR was lower for AI first for the ≤5 mm (15.9% vs 35.8%; OR, 0.34; 95% CI, 0.21-0.55) and nonpolypoid lesions (16.8% vs 45.8%; OR, 0.24; 95% CI, 0.13-0.43), and it was lower both in the proximal (18.3% vs 32.5%; OR, 0.46; 95% CI, 0.26-0.78) and distal colon (10.8% vs 32.1%; OR, 0.25; 95% CI, 0.11-0.57). Mean number of adenomas at second colonoscopy was lower in the AI-first group as compared with non-AI colonoscopy first (0.33 ± 0.63 vs 0.70 ± 0.97, P < .001). False negative rates were 6.8% (3 of 44 patients) and 29.6% (13 of 44) in the AI and non-AI first arms, respectively (OR, 0.17; 95% CI, 0.05-0.67). No difference in the rate of adverse events was found between the 2 groups. CONCLUSIONS:AI resulted in an approximately 2-fold reduction in miss rate of colorectal neoplasia, supporting AI-benefit in reducing perceptual errors for small and subtle lesions at standard colonoscopy. CLINICALTRIALS:gov, Number: NCT03954548.

Objectives: In this study, we aimed to characterize the SARS-CoV-2-specific T cell response detected by the QuantiFERON SARS-CoV-2 research use only assay in terms of accuracy and T cell subsets involved compared with a homemade interferon (IFN)-γ release assay (IGRA).Methods: We evaluated T cell response by the standardized QuantiFERON SARS-CoV-2 tubes (antigen [Ag]1 and Ag2) and a homemade IGRA quantifying IFN-γ response to SARS-CoV-2 spike peptides (homemade-IGRA-SPIKE test). We evaluated the T cell subsets mediating the specific response using flow cytometry.Results: We prospectively enrolled 66 individuals: COVID-19 or post-COVID-19 subjects and NO-COVID-19-vaccinated subjects, including healthy donors and immunocompromised subjects. The standardized kit detected 62.1% (41/66) of T cell responders. Ag2 tube showed a higher IFN-γ quantitative and qualitative response. Ag1 tube response was mainly mediated by CD4+ T cells; Ag2 tube response was mediated by CD4+ and CD8+ T cells. The homemade-IGRA-SPIKE test detected a higher number of responders (52/66, 78.8%) than the QuantiFERON SARS-CoV-2 assay (P = 0.056). The response was found in both T cell subsets, although a higher magnitude and response rate was observed in the CD4+ T cell subset.Conclusion: The QuantiFERON SARS-CoV-2 response is mediated by CD4+ and CD8+ T cells. A lower number of responders is found compared with the homemade-IGRA-SPIKE test, likely because of the different peptide composition.

BACKGROUND & AIMS:Artificial Intelligence (AI) could support cost-saving strategies for colonoscopy because of its accuracy in the optical diagnosis of colorectal polyps. However, AI must meet predefined criteria to be implemented in clinical settings. METHODS:An approved computer-aided diagnosis (CADx) module for differentiating between adenoma and nonadenoma in unmagnified white-light colonoscopy was used in a consecutive series of colonoscopies. For each polyp, CADx output and subsequent endoscopist diagnosis with advanced imaging were matched against the histology gold standard. The primary outcome was the negative predictive value (NPV) of CADx for adenomatous histology for ≤5-mm rectosigmoid lesions. We also calculated the NPV for AI-assisted endoscopist predictions, and agreement between CADx and histology-based postpolypectomy surveillance intervals according to European and American guidelines. RESULTS:Overall, 544 polyps were removed in 162 patients, of which 295 (54.2%) were ≤5-mm rectosigmoid histologically verified lesions. CADx diagnosis was feasible in 291 of 295 (98.6%), and the NPV for ≤5-mm rectosigmoid lesions was 97.6% (95% CI, 94.1%-99.1%). There were 242 of 295 (82%) lesions that were amenable for a leave-in-situ strategy. Based on CADx output, 212 of 544 (39%) would be amenable to a resect-and-discard strategy, resulting in a 95.6% (95% CI, 90.8%-98.0%) and 95.9% (95% CI, 89.8%-98.4%) agreement between CADx- and histology-based surveillance intervals according to European and American guidelines, respectively. A similar NPV (97.6%; 95% CI, 94.8%-99.1%) for ≤5-mm rectosigmoids was achieved by AI-assisted endoscopists assessing polyps with electronic chromoendoscopy, with a CADx-concordant diagnosis in 97.2% of cases. CONCLUSIONS:In this study, CADx without advanced imaging exceeded the benchmarks required for optical diagnosis of colorectal polyps. CADx could help implement cost-saving strategies in colonoscopy by reducing the burden of polypectomy and/or pathology. CLINICALTRIALS:gov registration number: NCT04884581.

Background To compare the performances of Infliximab (IFX) biosimilar CT-P13 and SB2 in the treatment of Inflammatory Bowel Diseases (IBD) outpatients in Italy. Research Design and Methods Three hundred and eighty IBD outpatients were retrospectively evaluated. The primary endpoint was to compare the two IFX biosimilars in terms of reaching and maintenance of remission at any timepoint. Results 197 patients with Ulcerative Colitis (UC) and 183 patients with Crohn's Disease (CD) treated with CT-P13 or SB2 and having a median (IQR) follow-up of 12 (6-36) months were compared: 230 (60.5%) were naive to anti-TNF alpha, 20 (5.26%) were switched from IFX originator or from IFX CT-P13 to IFX SB2. Clinical remission was achieved in 133 (67.5%) UC patients and in 164 (89.6%) CD patients (p < 0.000), with no differences between CT-P13 and SB2 in the rate of remission in UC (p = 0.667) and CD (p = 0.286). Clinical response, steroid-free remission, rate of surgery, mucosal healing (MH) in UC, switching from IFX originator or from other biosimilar, and safety were similar. Higher MH rate was obtained in CD patients treated with CT-P13 (p = 0.004). Conclusion This first comparative study found that both IFX biosimilars CT-P13 and SB2 are effective and safe in managing IBD outpatients.

The widespread diffusion of the coronavirus disease 2019 (COVID-19) has been one of the most dramatic challenges for health-care systems worldwide. Because of the huge number of symptomatic patients requiring hospitalization and intensive care treatment for severe COVID-19, most hospitals had to reset their priorities and to adapt their clinical activities to the management of patients affected by COVID-19. Several units have been reconverted into COVID-19 facilities, requiring the recruitment of medical and nursing staff taken from both medical and surgical departments; this rapid reorganization of service provision has led to a significant impact on daily health care for patients affected by other medical conditions, particularly patients with chronic diseases requiring long-term regular use of health-care resources. In Italy, a substantial change of practice has been recorded in most Gastroenterology Units through the entire country: although urgent and emergent services have been generally guaranteed, outpatient consultations, endoscopic and ultrasound procedures have been significantly reduced and limited to urgencies and oncologic indications [1Maida M. Sferrazza S. Savarino E. et al.Impact of the COVID-19 pandemic on gastroenterology divisions in Italy: a national survey.Dig Liver Dis. 2020; 52: 808-815Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar]. The restructuring of clinical activities also affected inflammatory bowel disease (IBD) units, most of them temporarily stopped and postponed non-urgent activities and implemented virtual follow-up clinics (telemedicine, phone calls and/or Email consultation) in order to reduce the risk of viral transmission while maintaining the minimum standard of IBD care [2Saibeni S. Scucchi L. Dragoni G. et al.Activities related to inflammatory bowel disease management during and after the coronavirus disease 2019 lockdown in Italy: how to maintain standards of care.United European Gastroenterol J. 2020; 8: 1228-1235Crossref PubMed Scopus (15) Google Scholar]. Little is known about the potential impact of these restructuring activities on IBD-related outcomes such as risk of flare, complications, hospitalization or surgery. Emerging data suggest a potential collateral damage caused by the COVID-19 pandemic because of a decline in seeking medical attention and/or hospital admissions from several other conditions. A reduced rate of hospital admissions for acute coronary syndrome during Covid-19 outbreak has been reported in northern Italy as well as in the United States [3De Filippo O. D'Ascenzo F. Angelini F. et al.Reduced rate of hospital admissions for ACS during Covid-19 outbreak in Northern Italy.N Engl J Med. 2020; 383: 88-89Crossref PubMed Scopus (798) Google Scholar,4Solomon M.D. McNulty E.J. Rana J.S. et al.The Covid-19 pandemic and the incidence of acute myocardial infarction.N Engl J Med. 2020; 383: 691-693Crossref PubMed Scopus (520) Google Scholar] and an inflation in acute cardiovascular deaths, not related to COVID-19 infection, has been reported, probably because patients were not promptly referred to hospital during the pandemic [5Wu J. Mamas M.A. Mohamed M.O. et al.Place and causes of acute cardiovascular mortality during the COVID-19 pandemic.Heart. 2021; 107: 113-119Crossref PubMed Scopus (127) Google Scholar]. Moreover, a reduction in the number of patients diagnosed with various gastro-intestinal cancers has been reported as a consequence of the substantial drop in endoscopy services [6Lui T.K.L. Leung K. Guo C.G. et al.Impacts of the coronavirus 2019 pandemic on gastrointestinal endoscopy volume and diagnosis of gastric and colorectal cancers: a population-based study.Gastroenterology. 2020; 159: 1164-1166Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar,7Khan A. Bilal M. Morrow V. et al.Impact of the coronavirus disease 2019 pandemic on gastrointestinal procedures and cancers in the United States: a multicenter research network study.Gastroenterology. Mar 2021; ([Epub ahead of print])https://doi.org/10.1053/j.gastro.2021.02.055Abstract Full Text Full Text PDF Scopus (24) Google Scholar]; an increase in cancer deaths because of delay in diagnosis and screening procedures is expected in the near future [8Maringe C. Spicer J. Morris M. et al.The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: a national, population-based, modelling study.Lancet Oncol. 2020; 21: 1023-1034Abstract Full Text Full Text PDF PubMed Scopus (1100) Google Scholar,9Ricciardiello L. Ferrari C. Cameletti M. et al.Pandemic on colorectal cancer screening delay: effect on stage shift and increased mortality.Clin Gastroenterol Hepatol. Sep 2020; ([Epub ahead of print])https://doi.org/10.1016/j.cgh.2020.09.008Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar]. We aimed to investigate if the reorganization of our IBD Unit and resetting clinical activities during the lockdown period has had an impact on IBD-related outcomes in the post lockdown phase. Our IBD Unit cares for 2500 patients; a dedicated outpatient clinic, including first visits and scheduled follow up visits, takes place every day of the week. An operational room for the administration of biotechnological drugs and dedicated endoscopic sessions are also available. Our Gastroenterology ward includes 16 beds for patients with any gastroenterological disease referred by the Emergency Room, outpatients clinics or other hospitals. IBD patients who require hospitalization for acute, severe disease, can be admitted directly to the gastroenterology ward. Finally, a dedicated phone line is available to allow patients direct contact with the IBD medical staff if necessary. We have compared our IBD Unit activities (number of outpatients visits and endoscopies) performed during lockdown (March 2020 to May 2020) with the same period of the previous year. Then we have analyzed outpatients visits in the 7 months post lockdown period (June to December 2020) comparing these data with the same period of 2019. Month by month, we have classified patients in: 1) clinical remission; 2) mild disease activity; 3) moderate disease activity; and 4) severe disease activity, according to treatment decisions during each visit: no therapeutic changes = clinical remission; new prescription of aminosalicylates or aminosalicylates optimization = mild disease activity; prescription of systemic or low bioavailability steroids = moderate disease activity; new prescription of immunomodulators (IMMs) or biologics, biologic dose intensification or switch, hospital admission or surgical procedure = severe disease activity. Differences in the distribution of disease activity between the two periods in 2020 and 2019 have been analyzed using the chi square test. During lockdown outpatients follow up visits have been reduced by 37% compared to the same period in 2019 (405 vs 639). Elective endoscopic procedures have been reduced by 54.5% in the same period compared to 2019 (Fig. 1). Conversely, all patients receiving biologic therapies (both intravenous and subcutaneous) were regularly evaluated at scheduled intervals and scheduled infusions were maintained with no delay. Patients requiring hospitalization were regularly admitted to our gastroenterology ward. The decision of postponing follow up visits or endoscopic procedures was made on a case-by-case basis after a phone contact with the patient in which symptoms, laboratory tests and adherence to treatment were accurately assessed and recorded. In the 7 months post lockdown our IBD unit activity gradually returned toward normality; the number of follow up visits (1368 visits performed in 627 patients) was similar to the same period in 2019 (1329 visits performed in 636 patients). The distribution of disease activity month by month is shown in Fig. 2. No difference is observed compared to the same period of 2019. Although in August 2020, compared to August 2019, we have observed a significantly higher proportion of patients with active disease requiring escalation of therapy (38.3% vs 22.2%; p = 0.01), most of these patients had mild disease activity requiring only aminosalicylates optimization; no significant difference is observed in the proportion of patients with moderate to severe disease activity (23.4% vs 14.8%; p = 0.1). Compared to 2019, no significant differences have been observed in the number of urgent hospitalizations (46 vs 36; p = 0.2) or surgeries (22 vs 17; p = 0.3)Fig. 2Distribution of disease activity month by month in the post lockdown period and in the corresponding period in 2019.View Large Image Figure ViewerDownload Hi-res image Download (PPT) In summary, in our experience, restructuring clinical activities during lockdown had no significant impact on IBD clinical outcomes in the post lockdown phase. Some considerations can help to explain our results. The first one is how we have reset our priorities without reducing the level of care below acceptable standards for IBD patients. According to our Regional Health AuthoritY, during the lockdown period, in order to reduce the risk of transmission, outpatients' visits had to be limited only to those considered "urgent" according to the priorities code of the Italian health system (i.e. requiring medical assistance within 72 h or 10 days). In our opinion, these strict "urgency criteria" do not perfectly fit all IBD patients especially in the light of recent medical strategies such as early intervention, treat-to target and tight monitoring approaches [10Pugliese D. Papi C. Privitera G. et al.The management of inflammatory bowel diseases in the era of COVID-19 pandemic: when "non-urgent" does not mean "deferrable".Dig Liver Dis. 2020; 52: 1238-1240Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar]. According to this point of view, many "non urgent" interventions have been considered not deferrable and were regularly done. For example, patients in clinical remission ("non urgent" by definition) but requiring prompt evaluation and tight follow-up for planning long-term strategies have been regularly evaluated in a face-to-face setting. Secondly, we have implemented virtual follow-up using phone calls with a tailored approach. In fact, the decision of postponing follow up visits or endoscopic procedures was made on strict case by case criteria, after evaluation of symptoms, laboratory tests and adherence to treatment and taking into account the general course of the disease in individual patients. This approach allowed us to reschedule all procedures (visits or endoscopies) only in low-risk patients without negative impact on IBD-related outcomes. To our knowledge this is the first experience exploring the impact of restructuring an IBD unit during pandemic on IBD-related outcomes in the post lockdown period. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Fabiola De Biasio: none Annalisa Aratari: None Stefano Festa has received consultancy fees and/or educational grants from Takeda, Sofar, Janssen Cilag Abbvie, Zambon. Roberto Lorenzetti: none Claudio Papi has received consultancy fees and/or educational grants from Abbvie, MSD, Takeda, Pfizer, Janssen-Cilag, Chiesi, Sofar, Ferring and Zambon. No other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Background: Infliximab and adalimumab are widely used for the treatment of Crohn's disease and ulcerative colitis. Aim: To compare the long-term efficacy and safety of infliximab and adalimumab in a large cohort of Crohn's disease and ulcerative colitis patients reflecting real-life clinical practice. Methods: Seven hundred twelve patients were retrospectively reviewed, 410 with Crohn's disease (268 treated with adalimumab and 142 with infliximab; median follow-up 60 months, range, 36-72) and 302 with ulcerative colitis (118 treated with adalimumab and 184 with infliximab; median follow-up 48 months, range, 36-84). Results: In Crohn's disease, clinical remission was maintained in 75.0% of adalimumab vs. in 72.5% of infliximab patients (P = 0.699); mucosal healing and steroid-free remission were maintained in 49.5% of adalimumab vs. 63.9% of infliximab patients (P = 0.077) and in 77.7% of adalimumab vs. 77.3% in infliximab group (P = 0.957), respectively. In ulcerative colitis, clinical remission was maintained in 50.0% of adalimumab vs. 65.8% of infliximab patients (P < 0.000); mucosal healing and steroid-free remission were maintained in 80.6% of adalimumab vs. 77.0% of infliximab patients (P = 0.494) and in 90.2% of adalimumab vs. 87.5% of infliximab patients (P = 0.662), respectively. At the multivariate analysis, ileocolonic location and simple endoscopic score for Crohn's disease >10 were predictors of failure in Crohn's disease; treatment with adalimumab, BMI >= 30 and Mayo score >10 were predictors of failure in ulcerative colitis. infliximab was more likely to cause adverse events than adalimumab (16.6 vs. 6.2%, P < 0.000). Conclusion: Both adalimumab and infliximab are effective in long-term outpatients management of inflammatory bowel diseases. Adalimumab had a lower rate of adverse events.

BACKGROUND AND AIMS:Adequate bowel cleansing is critical to ensure quality and safety of a colonoscopy. A novel 1-L polyethylene glycol plus ascorbate (1L-PEG+ASC) regimen was previously validated against low-volume regimens but was never compared with high-volume regimens.METHODS:In a phase IV study, patients undergoing colonoscopy were randomized 1:1 to receive split-dose 1L PEG+ASC or a split-dose 4-L PEG-based regimen (4L-PEG) in 5 Italian centers. Preparation was assessed with the Boston Bowel Preparation Scale (BBPS) by local endoscopists and centralized reading, both blinded to the randomization arm. The primary endpoint was noninferiority of 1L-PEG+ASC in colon cleansing. Secondary endpoints were superiority of 1L-PEG+ASC, patient compliance, segmental colon cleansing, adenoma detection rate, tolerability, and safety.RESULTS:Three hundred eighty-eight patients (median age, 59.8 years) were randomized between January 2019 and October 2019: 195 to 1L-PEG+ASC and 193 to 4L-PEG. Noninferiority of 1L-PEG+ASC was demonstrated for cleansing in both the entire colon (BBPS ≥ 6: 97.9% vs 93%; relative risk [RR], 1.03; 95% confidence interval [CI], 1.001-1.04; P superiority = .027) and in the right-sided colon segment (98.4% vs 96.0%; RR, 1.02; 95% CI, .99-1.02; P noninferiority = .013). Compliance was higher with 1L-PEG+ASC than with 4L-PEG (178/192 [92.7%] vs 154/190 patients [81.1%]; RR, 1.10; 95% CI, 1.05-1.12), whereas no difference was found regarding safety (moderate/severe side effects: 20.8% vs 25.8%; P = .253). No difference in adenoma detection rate (38.8% vs 43.0%) was found.CONCLUSIONS:One-liter PEG+ASC showed noninferiority compared with 4L-PEG in achieving adequate colon cleansing and provided a higher patient compliance. No differences in tolerability and safety were detected. (Clinical trial registration number: NCT03742232.).

INTRODUCTION AND AIM:Biologic treatment - particularly with the anti-TNF molecules - is frequently used in clinical practice to treat the severe form for both chronic rheumatic diseases and inflammatory bowel diseases. The immunosuppression induced by biologic therapies increases the risk of infections, including tuberculosis, as well as hepatitis B virus (HBV) reactivation may occur in inactive carriers or occult HBV infection (OBI) subjects during biologic therapy. This study aimed to update data on HBV prevalence and reactivation in patients receiving biologic therapy for either chronic rheumatic diseases or IBD, and to describe their management in clinical practice.MATERIALS AND METHODS:This study was performed in 6 Italian centers (3 Rheumatology Units and 3 Gastroenterology Units). Clinical, biochemical and virological data, as well as follow up information, were recorded and analyzed.RESULTS:984 patients were considered, including 817 with rheumatic disease and 167 with IBD. A total of 43 showed HBV infection (38 OBI and 5 carriers) accounting for a prevalence of 4%. Among OBI patients, 1 (2.6%) case of HBV reactivation occurred in a male patient with Crohn disease. Among the 5 HBV carriers, two patients (1 with spondyloarthritis and 1 with rheumatoid arthritis) did not received HBV antiviral therapy, and both experienced flare of hepatitis at 47 and 49 months following biologic therapy starting.DISCUSSION:Data of our study highlight that guidelines on management of HBV patients treated with biologic therapies should be still implemented in clinical practice when considering that, although infrequent, HBV reactivation could be potentially life-threatening.

OBJECTIVE: Ustekinumab (UST) is an anti-IL12/23 antibody for the treatment of Crohn’s Disease (CD). The aim of this study was to compare the efficacy and safety of UST in a large population-based cohort of CD patients who failed previous treatment with other biologics. PATIENTS AND METHODS: 194 CD patients (108 males and 86 females, mean age 48 years (range 38-58 years) were retrospectively reviewed. 147 patients were already treated with anti-TNFα (75.8%), and 47 (24.2%) patients were already treated with anti-TNFα and vedolizumab. Concomitant treatment with steroids was present in 177 (91.2%) patients. RESULTS: At week 12, clinical remission was achieved in 146 (75.2%) patients. After a mean follow-up of 6 months, clinical remission was maintained in 135 (69.6%) patients; at that time, mucosal healing was assessed in 62 (31.9%) patients, and it was achieved in 33 (53.2) patients. Three (1.5%) patients were submitted to surgery. Steroid-free remission was achieved in 115 (59.3%) patients. Both serum C-Reactive Protein and Fecal Calprotectin (FC) levels were significantly reduced with respect to baseline levels during follow-up. A logistic regression, UST therapy as third-line therapy (after both anti-TNFα and vedolizumab), FC >200 µg/g, and HBI ≥8 were significantly associated with lack of remission. Adverse events occurred in 5 (2.6%) patients, and four of them required suspension of treatment. CONCLUSIONS: UST seemed to be really effective and safe in CD patients unresponsive to other biologic treatments, especially when used as second-line treatment.