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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.

Comparative trials among biological drugs for the treatment of ulcerative colitis (UC) provided conflicting results. After patent expire of infliximab originator, adalimumab, infliximab biosimilar, golimumab and vedolizumab have been approved in Italy.We compared the efficacy of these four biologics in UC according to the concept of continuous clinical remission (CCR).In a retrospective, multicentre study, all UC patients treated with adalimumab, infliximab biosimilar, golimumab or vedolizumab between 2014 and 2019 were included. All drugs were compared to each other according to the 1-year CCR rate, defined as Mayo partial score ≤2, with bleeding subscore = 0, without any relapse or optimization with dose escalation, topical treatments or steroid use after first clinical remission.Four-hundred sixteen patients (adalimumab = 90, infliximab biosimilar = 105, golimumab = 79, vedolizumab = 142) were included. CCR was achieved in similar percentages among the groups (33%, 37%, 28%, 37%, respectively). All drugs were equivalent in biologic-naive patients, while vedolizumab was better than a second anti-TNFα in prior anti-TNFα agent failures. No differences were found according to type of adverse events or severe adverse events.Based on a strict definition of clinical remission, all biologics appear equally effective at 1 year. Changing to vedolizumab is more effective than switching to another anti-TNFα in TNFα failures.

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: A treat-to-target strategy, in which strictly defined treatment targets facilitate decision making in clinical practice, is advocated as an optimised management approach for some chronic disorders. The aim of the STARDUST trial was to assess whether a treat-to-target strategy with early endoscopy, regular biomarker and clinical symptom monitoring, and dose intensification for persistent inflammatory activity, was more successful in achieving endoscopic improvement at week 48 than a clinically driven maintenance strategy in patients with moderate-to-severe active Crohn's disease receiving ustekinumab. Methods: This open-label, multicentre, randomised phase 3b trial included adults with active, moderate-to-severe Crohn's disease (Crohn's Disease Activity Index [CDAI] 220–450 and Simple Endoscopic Score in Crohn's Disease [SES-CD] ≥3) for whom conventional therapy or one biologic therapy, or both, had failed. Patients received intravenous ustekinumab approximating 6 mg/kg at baseline and subcutaneous ustekinumab 90 mg at week 8. At week 16, patients with a CDAI improvement of 70 or more points from baseline were randomly assigned (1:1) to receive standard-of-care or treat-to-target maintenance treatment through week 48. Randomisation was balanced by using randomly permuted blocks and was stratified by biologic history status and baseline SES-CD score. All patients who signed informed consent, who were not screening failures, and who received at least one dose of study treatment were included in week 16 analyses. All patients included in week 16 analyses and randomly assigned to one of the maintenance treatment regimens were included in the week 48 efficacy and safety analyses (ie, on an intention-to-treat basis). Patients assigned to the treat-to-target arm received ustekinumab every 12 weeks or every 8 weeks based on SES-CD improvement from baseline and could escalate to every 4 weeks through week 48 if prespecified targets were missed. Patients assigned to the standard-of-care arm received ustekinumab every 12 weeks or every 8 weeks; those receiving treatment every 12 weeks could escalate per European labelling. The primary efficacy endpoint was endoscopic response at week 48 (SES-CD score ≥50% decrease from baseline), analysed by non-responder imputation. This trial is registered at ClinicalTrials.gov, NCT03107793, and is active but not recruiting. Findings: 498 patients received standard induction treatment, of whom 440 were randomly assigned to the treat-to-target group (n=219) or the standard-of-care group (n=221). At week 48, there was no significant difference in endoscopic response (83 [38%] of 219 patients vs 66 [30%] of 221 patients; p=0·087), endoscopic remission (25 [11%] vs 32 [15%]; p=0·334), mucosal healing (31 [14%] vs 37 [17%]; p=0·449), and clinical remission (135 [62%] vs 154 [70%]; p=0·072) between the two groups; clinical response was significantly lower in the treat-to-target group than in the standard-of-care group (149 [68%] vs 172 [78%]; p=0·020). Other endoscopic, clinical, and biomarker outcomes were generally not significantly different between groups. The most commonly reported treatment-emergent adverse events were nasopharyngitis (29 [13%] of 219 patients in the treat-to-target group vs 29 [13%] of 221 patients in the standard-of-care group), abdominal pain (23 [11%] vs 19 [9%]), arthralgia (24 [11%] vs 19 [9%]), and headache (24 [11%] vs 21 [10%]). Interpretation: Timely escalation of ustekinumab therapy for patients with Crohn's disease, based on early endoscopic response, clinical symptoms, and biomarkers, did not result in significantly better endoscopic outcomes at week 48 than symptom-driven decisions alone. Future studies need to confirm if some subgroups of patient might benefit from a treat-to-target strategy with ustekinumab. Funding: Janssen-Cilag.

Background Little is known about the unmet needs of physicians caring for patients with inflammatory bowel disease (IBD). Aims This study explored the practical difficulties and needs for professional updating of Italian IBD physicians. Methods A questionnaire was distributed to 600 physicians attending IG-IBD meetings. Results 280 physicians completed the questionnaire (46.7%). On a 5-point Likert scale (from 1, strongly disagree to 5, strongly agree), they identified the most problematic issues in managing IBD patients as increasing bureaucracy (3.9), lack of extra-gastroenterological IBD expertise (3.4), lack of diagnostic techniques (3.1) and budget limitations (2.9). The most lacking techniques, ranked from 1 (greatest need) to 9 (lowest need), were: anti-drug antibody and trough level assays (2.7), device-assisted enteroscopy (3.1), exploration under anaesthesia (3.2), MR enterography (3.2), and bowel ultrasonography (3.3). About professional updating, respondents indicated (on a 5-point Likert scale) that helpful topics were practical medicine (4.3), managing difficult patients (4.1), and guidelines (4.0). The most desired modality for updating was residential courses on clinical practice (4.3). Conclusion Several factors potentially limit the best management of IBD patients in Italy. Satisfying these unmet needs could improve care for IBD patients.

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.

Background Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), with a 6% to 74% prevalence and a negative impact on patient survival and quality of life, although the prevalence is apparently declining due to improved disease treatment. We aimed to investigate the prevalence, pathogenesis, and clinical correlates of anemia in Italian patients with IBD. Methods A multicenter, prospective, observational study, involving 28 Italian gastroenterology centers, was conducted to investigate the epidemiology and consequences of IBD-associated anemia. Clinical and laboratory data of anemic patients were obtained at study enrolment. Results Anemia was diagnosed in 737 of 5416 adult IBD outpatients (prevalence 13.6%); females were more commonly affected than males (odds ratio, 1.5; 95% confidence interval [CI], 1.2–1.7) and had more severe anemia. In the majority of cases, anemia was due to iron deficiency (62.5% of cases; 95% CI, 58.3%–66.6%), either isolated or in association with inflammation and/or vitamin deficiencies; anemia of inflammation accounted for only 8.3% of cases. More severe anemia was associated with increasing fatigue and worse quality of life. Only 68.9% of anemic patients with iron deficiency (95% CI, 63.4%–73.8%) and 34.6% of those with vitamin deficiencies (95% CI, 26.2%–44.2%) were properly treated with supplementation therapy. Conclusions In Italy, the prevalence of IBD-associated anemia is lower than previously reported. Anemia of IBD is most commonly due to iron deficiency and contributes to fatigue and poor quality of life, but remains untreated in a large proportion of patients with iron and/or vitamin deficiencies. This study is registered at clinicaltrials.gov as NCT02872376.

Summary Background Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. Methods HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18–80 years) patients 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) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have 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. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (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) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov , NCT02100696 . Findings HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). Interpretation HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. Funding F Hoffmann-La Roche.

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 Reducing the morning dose of PEG solution may be a reliable strategy to improve the patient compliance of split-dose regimens without affecting efficacy of bowel cleansing. Aims to compare the efficacy for bowel cleansing of an asymmetric split-dose regimen (25% of the dose on the day of colonoscopy and 75% on the day before) with the standard split-dose regimen. Methods Outpatients were enrolled in a randomized, single-blind, non-inferiority clinical trial. All subjects received a split-dose preparation with a 2L PEG-citrate-simethicone plus Bisacodyl. Patients were randomly assigned to: group A, asymmetric split-dose regimen; group B, symmetric split-dose regimen. Primary endpoint was the proportion of adequate bowel cleansing. Results Split-dose was taken by 81 and 80 patients in group A and B. Adequate bowel cleansing was achieved in 92.6% and 92.5% patients in group A and B (p = 1.000). No differences were observed regarding Boston Bowel Preparation Scale total score, adenoma detection rate and scores of each colon segment. Conclusions The reduction of morning dose of PEG in a split-dose regimen is not inferior to the standard split-dose regimen in achieving an adequate bowel cleansing. However, further studies are needed to evaluate whether asymmetric preparation is associated to a higher tolerability compared to symmetric split-dose regimen. (NCT03146052)

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.

Background Inflammatory bowel disease (IBD) is usually diagnosed in subjects with gastrointestinal symptoms, but may also be asymptomatic and diagnosed incidentally. Aims to determine the prevalence of IBD in asymptomatic adults. Methods we identified subjects who underwent colonoscopy between 1 September 2013 and 31 August 2019 in a regional colorectal cancer screening program with endoscopic findings suggestive of IBD, and retrieved their clinical, histological and therapeutic information. Results 5116 subjects underwent colonoscopy, and 4640 persons were considered assessable. Of these, 54 (1.16%) had endoscopic findings suggestive of IBD, including 40 of Crohn's disease (CD) and 14 of ulcerative colitis (UC). A definite diagnosis of IBD was made in 19 patients, for an overall IBD prevalence of 0.41%, with 13 cases of CD (0.28%) and 6 of UC (0.13%). The mean follow-up was 26.8 months after the first colonoscopy. Therapy was started in 5 of 13 CD patients and all UC patients. Conclusion Endoscopic findings suggestive of IBD are not infrequent in an asymptomatic colorectal cancer screening population. Visualization of the terminal ileum is recommended in this setting. A definite diagnosis of IBD was made in about 1 out of 3 subjects with endoscopic lesions. Most IBD patients had a mild form of disease, but some needed biologic therapy.

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.

Introduction The most typical presentation of COVID-19 is an acute respiratory syndrome whose most common symptoms include fever, cough, and dyspnea. However, gastrointestinal symptoms, such as diarrhea and nausea/vomiting, are increasingly reported in patients affected by COVID-19. This study aimed to describe the prevalence and time of onset of gastrointestinal symptoms in patients affected by COVID-19 and to find potential associations between gastrointestinal symptoms and clinical outcomes. Methods We performed a prospective single-center cohort study, enrolling patients who received diagnosis of COVID-19 at our institution between March 23, 2020, and April 5, 2020. We collected patient demographics and medical history, laboratory data, and clinical outcomes. Furthermore, we used a specifically designed questionnaire, administered to patients at time of diagnosis, to obtain data on the presence and time of onset of fever, typical respiratory symptoms, gastrointestinal symptoms, and other symptoms (fatigue, headache, myalgia/arthralgia, anosmia, ageusia/dysgeusia, sore throat, and ocular symptoms). Results In our cohort, 138 (69%) of 190 patients showed at least 1 gastrointestinal symptom at diagnosis; if excluding hyporexia/anorexia, 93 patients (48.9%) showed at least 1 gastrointestinal symptom. Gastrointestinal symptoms, in particular diarrhea, were associated with a lower mortality. At multivariate analysis, diarrhea was confirmed as independent predictive factor of lower mortality. Discussion Gastrointestinal symptoms are very frequent in patients with COVID-19 and may be associated with a better prognosis. These data suggest that, in some patients, the gastrointestinal tract may be more involved than the respiratory system in severe acute respiratory syndrome coronavirus 2 infection, and this could account for the less severe course of disease.

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

Background Acute gastrointestinal bleeding (AGIB) results in significant morbidity and mortality. Topical hemostatic products have been developed for endoscopic use to help in the management of difficult bleeding. Our aim was to demonstrate the ease of use, safety, and efficacy of PuraStat, a novel hemostat, to control AGIB. Methods We describe 77 patients (41 men) who were treated for acute upper and lower AGIB in a 2-year period. In 50 patients, bleeding occurred as a complication of a previous endoscopic procedure, predominantly endoscopic mucosal resection (EMR) and endoscopic retrograde cholangiopancreatography (ERCP); however, in the other 27 patients, it derived from peptic ulcers, angiodysplasia, cancers, and surgical anastomoses. Bleeding was spurting in 13 of the 77 patients and oozing in 64. PuraStat was used after the failure of at least two conventional hemostatic methods. Results A mean of 2.6 conventional hemostatic methods had been attempted prior to the application of PuraStat. PuraStat achieved successful hemostasis in 90.9 % of patients. In 41 patients, once hemostasis was obtained with PuraStat, endoscopists further stabilized hemostasis by using at least one additional method. Recurrence of bleeding was observed in eight patients (10.4 %). In 16 patients with intraprocedural bleeding, it was possible to complete the procedures (14 EMR, 2 ERCP) after PuraStat hemostasis. No adverse events related to PuraStat were recorded. Conclusions PuraStat is feasible, safe, and effective in controlling different types of gastrointestinal hemorrhage after failure of conventional hemostatic methods. Its application also does not hinder continuing endotherapy.

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.