Efficacy of 1 L polyethylene glycol plus ascorbate versus 4 L polyethylene glycol in split-dose for colonoscopy cleansing in out and inpatient: A multicentre, randomized trial (OVER 2019).

BACKGROUND AND AIMS: Adequate bowel cleansing is essential for colonoscopy quality. A novel 1 L polyethylene glycol plus ascorbate (1 L PEG+ASC) solution has been recently introduced. Nevertheless, the efficacy of 1 L PEG+ASC as compared to that of high-volume bowel preparation in both inpatients and outpatients is still unclear. PATIENTS AND METHODS: This single-blinded, non-inferiority study randomized patients undergoing colonoscopy to receive split-dose 1 L PEG+ASC or 4 L PEG. The primary endpoint was the overall cleansing success. Secondary endpoints were excellent cleansing and high-quality cleansing of the right colon, as well as lesions detection rate, patient compliance, tolerability and safety. RESULTS: Overall, 478 patients were randomized to 1 L PEG+ASC (N = 236) or 4 L PEG (N = 242). The 1 L PEG+ASC showed higher cleansing success rate (91.8% vs 83.6%; P=0.01) and a high-quality cleansing of the right colon (52.3% and 38.5%; P=0.004) compared to 4 L PEG. Moreover, 1 L PEG+ASC achieved a higher cleansing success in out-patients (96.3%% vs 88.6%; P=0.018), and a similar success rate in the in-patients (84.7% vs 76.7%; P=0.18). Adenoma detection rate, tolerability and incidence of adverse events were comparable between preparations. CONCLUSIONS: The 1 L PEG+ASC showed higher efficacy in achieving adequate colon cleansing compared with 4 L PEG, particularly in the right colon. No differences in the tolerability and safety were detected.

Severe Activity of Inflammatory Bowel Disease is a Risk Factor for Severe COVID-19.

BACKGROUND: Data from the first wave of the coronavirus disease 2019 (COVID-19) pandemic suggested that patients with inflammatory bowel disease (IBD) are not at higher risk of being infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population and that a worse prognosis is not associated with immunomodulatory drugs, with the possible exception of systemic steroids. METHODS: This retrospective, observational study included consecutive IBD patients from the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) cohort who had a SARS-CoV-2 infection diagnosis (polymerase chain reaction-confirmed presence of the viral genome in a nasopharyngeal swab) during the second COVID-19 pandemic wave (September 2020 to December 2020). Data regarding demographics, IBD features and treatments, and comorbidities were analyzed in correlation with COVID-19 clinical outcomes. RESULTS: Data on 122 patients (mean age, 43.9 ±â€…16.7 years; males, 50.0%; Crohn's disease, 62.3%; ulcerative colitis, 37.7%) were reported. Twelve patients developed COVID-19-related pneumonia (9.8%), 4 (3.3%) required respiratory assistance (nonmechanical ventilation or orotracheal intubation), and 4 died (case fatality rate, 3.3%). In a multivariable analysis, age (odds ratio [OR], 1.034; 95% CI, 1.006-1.147; P = .032) and severe IBD activity (OR, 13.465; 95% CI, 1.104-164.182; P = .042) were independent predictors of COVID-19-related pneumonia, while severe IBD activity (OR, 15.359; 95% CI, 1.320-178.677; P = .030) was the only independent predictor of severe COVID-19, a composite endpoint defined as the need for respiratory assistance or death. A trend towards a protective role of tumor necrosis factor α inhibitors on pneumonia development was reported (P = .076). CONCLUSIONS: In this cohort of patients with IBD and SARS-CoV-2 infection, severe IBD activity was the only independent risk factor for severe COVID-19.

This retrospective, observational study on patients with inflammatory bowel disease and severe acute respiratory syndrome coronavirus 2 infection showed that severe inflammatory bowel disease activity was the only independent risk factor for severe coronavirus disease 2019.

Vedolizumab may be an effective option for the treatment of postoperative recurrence of Crohn's disease.

BACKGROUND: The role of Vedolizumab (VDZ) as therapeutic option for the postoperative recurrence of Crohn's disease (CD) following ileocolonic resection is unknown. AIMS: To assess the effectiveness of VDZ in this setting. METHODS: All consecutive CD patients with a baseline colonoscopy at 6-12 months from the ileocolonic resection showing postoperative recurrence (Rutgeerts score ≥i2) and treated with VDZ after the baseline colonoscopy were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, assessed at the first colonoscopy following initiation of VDZ and defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical failure, assessed at one year and at the end of follow-up. RESULTS: Fifty-eight patients were included (mean follow-up: 24.8 ± 13.1 months). Endoscopic success was reported in 47.6% of patients. Clinical failure was reported in 19.0% of patients at one year, and in 32.8% of patients at the end of follow-up. A new resection was required in 7 patients (12.1%). CONCLUSIONS: VDZ may be an effective option for the treatment of postoperative recurrence of CD.

SPOSAB ABP 501: A Sicilian Prospective Observational Study of Patients with Inflammatory Bowel Disease Treated with Adalimumab Biosimilar ABP 501.

BACKGROUND AND AIM: There are few clinical data on Adalimumab (ADA) biosimilars in inflammatory bowel disease. We aimed to perform a multicenter, observational, prospective study on safety and effectiveness of ADA biosimilar ABP 501 in patients with inflammatory bowel disease. METHODS: All consecutive patients from the cohort of the Sicilian Network for Inflammatory Bowel Disease treated with ADA biosimilar ABP 501 from February 2019 to February 2020 were enrolled. Patients were divided into three groups: group A, naïve to ADA and naïve to anti-tumor necrosis factors; group B, naïve to ADA and previously exposed to anti-tumor necrosis factors; and group C: switched from ADA originator to ABP 501. RESULTS: A total of 559 patients (median age 39 years; Crohn's disease 88.0%, ulcerative colitis 12.0%) were included, with a follow-up time of 403.4 patient-years. Thirty-six serious adverse events occurred in 36 patients (6.4%; incidence rate [IR]: 8.9 per 100 person-years [PY]). The IR of serious adverse events was higher among patients in group A compared with group C (17.4 vs 4.8 per 100 PY; IR ratio = 3.61; P < 0.001) and among patients in group B compared with group C (16.4 vs 4.8 per 100 PY; IR ratio = 3.42; P = 0.041). Among ADA-naïve patients (group A + B), 188 (85.8%) had a clinical response after 12 weeks, including 165 (75.3%) who achieved steroid-free remission. Higher treatment persistence estimates were reported for patients in group C compared with groups A and B (log-rank P < 0.001). CONCLUSIONS: Safety and effectiveness of ABP 501 seem to be overall similar to those reported for ADA originator. Switching from originator to ABP 501 was safe and effective.

Ustekinumab in Crohn's disease: Real-world outcomes from the Sicilian network for inflammatory bowel diseases.

BACKGROUND AND AIM: Ustekinumab is approved in Europe for the treatment of moderate to severe Crohn's disease (CD). Italian real-life data are scarce, so the aim of this study was to assess the effectiveness and safety of ustekinumab in an Italian cohort of CD patients. METHODS: Data of patients with CD who started using ustekinumab were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. Primary end-points were steroid-free clinical remission at 8, 24, and 52 weeks of therapy and reduction of C-reactive protein. Secondary end-points were treatment response, treatment persistence at 12 months, and safety. RESULTS: A total of 131 patients (males 56%; mean age 46 years ±15) were included. All patients were biologics experienced except for one. At 24 and 52 weeks, 40% and 43% of patients achieved steroid-free clinical remission, and 64% and 62% had clinical response, respectively. At the end of follow-up, there was a significant reduction of steroid use (P = 0.012) and of the Harvey-Bradshaw Index (P = 0.001). The probability of persistence in therapy with ustekinumab after 12 months of treatment was 89%. The only factor associated with discontinuation was older age. CONCLUSIONS: Data from our real-life cohort of treatment-refractory CD patients suggest the satisfactory effectiveness and safety profile of ustekinumab.

The SPOSIB SB2 Sicilian Cohort: Safety and Effectiveness of Infliximab Biosimilar SB2 in Inflammatory Bowel Diseases, Including Multiple Switches.

BACKGROUND: No data on the recently introduced infliximab (IFX) biosimilar SB2 in inflammatory bowel disease (IBD) are available. METHODS: The Sicilian Prospective Observational Study of Patients With IBD Treated With Infliximab Biosimilar SB2 is a multicenter, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease. All consecutive IBD patients starting the IFX biosimilar SB2 from its introduction in Sicily (March 2018) to September 2019 (18 months) were enrolled. RESULTS: Two hundred seventy-six patients (Crohn disease: 49.3%, ulcerative colitis: 50.7%) were included: 127 (46.0%) were naïve to IFX and naïve to anti-tumor necrosis factor medications (anti-TNFs), 65 (23.5%) were naïve to IFX and previously exposed to anti-TNFs, 17 (6.2%) were switched from an IFX originator to SB2, 43 (15.6%) were switched from the biosimilar CT-P13 to SB2, and 24 (8.7%) were multiply switched (from IFX originator to CT-P13 to SB2). The cumulative number of infusions of SB2 was 1798, and the total follow-up time was 182.7 patient-years. Sixty-seven serious adverse events occurred in 57 patients (20.7%; incidence rate: 36.7 per 100 patient-year), and 31 of these events caused the withdrawal of the drug. The effectiveness after 8 weeks of treatment was evaluated in patients naïve to IFX (n = 192): 110 patients (57.3%) had steroid-free remission, while 56 patients had no response (29.2%). At the end of follow-up, 72 patients (26.1%) interrupted the treatment, without significant differences in treatment persistency estimations between the five groups (log-rank P = 0.15). CONCLUSIONS: The safety and effectiveness of SB2 seem to be overall similar to those reported for the IFX originator and CT-P13.

Effectiveness of Ustekinumab on Crohn's Disease Associated Spondyloarthropathy: Real-World Data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD).

BACKGROUND: The effectiveness of Ustekinumab (UST) on Crohn's disease (CD)-associated spondyloarthropathy (SpA) is currently unknown. RESEARCH DESIGN AND METHODS: All consecutive CD patients with active SpA at the initiation of the treatment with UST were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was the articular response at 8 and 24 weeks, defined as the disappearance of objective signs of arthritis (swelling and/or articular stiffness) and resolution of pain. RESULTS: Thirty CD patients with active SpA at the initiation of the treatment with UST were assessed. At 24 weeks, 13 patients (43.3%) had an articular response, including 10/18 patients (55.5%) with peripheral SpA and 3/9 patients (33.3%) with axial and peripheral SpA. No patient with axial SpA experienced an articular response. The drop of mean as Harvey-Bradshaw Index values from baseline to week 24 was higher in patients with articular response compared with non-responders (3.8 ± 2.4 vs. 1.3 ± 2.8, p = 0.02). CONCLUSIONS: Our real-world, multicentre experience showed that UST was able to obtain a response on articular symptoms in nearly half of the patients with CD and active SpA after 24 weeks of treatment.

A propensity score weighted comparison of Vedolizumab, Adalimumab, and Golimumab in patients with ulcerative colitis.

BACKGROUND: No real-life study on the comparative effectiveness of Vedolizumab (VDZ), Adalimumab (ADA), and Golimumab (GOL) in ulcerative colitis (UC) is currently available. AIMS: To compare the effectiveness of the three biologics in consecutive patients with UC. METHODS: A three-arms propensity score-adjusted analysis was performed using the Inverse Probability of Treatment Weighting method. RESULTS: 463 treatments (VDZ: n = 187; ADA: n = 168; GOL: n = 108) were included (median follow-up: 47.6 weeks). At 12 weeks (n = 463), a steroid-free remission was reported in 24.1% patients in the VDZ group, in 33.3% patients in the ADA group, and in 30.6% patients in the GOL group (p = n.s. for all comparisons). At 52 weeks (n = 377), a steroid-free remission was reported in 51.5% patients in the VDZ group, in 31.2% patients in the ADA group, and in 29.4% patients in the GOL group (p = 0.002 for VDZ vs. ADA, p = 0.001 for VDZ vs. GOL, p = n.s. for ADA vs. GOL). Cox survival analysis demonstrated that patients treated with VDZ had reduced probability of treatment discontinuation compared to those treated with ADA (HR: 0.42, 95% CI 0.28-0.64, p < 0.001) and GOL (HR: 0.30, 95% CI 0.19-0.46, p < 0.001), while patients treated with ADA had reduced risk of treatment discontinuation compared to those treated with GOL (HR: 0.71, 95% CI 0.50-1.00, p = 0.048). CONCLUSIONS: VDZ was superior to ADA and GOL at 52 weeks and as treatment persistence, while ADA showed a superior treatment persistence compared to GOL.

Persistence on Anti-Tumour Necrosis Factor Therapy in Older Patients with Inflammatory Bowel Disease Compared with Younger Patients: Data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD).

BACKGROUND AND OBJECTIVE: Older people with inflammatory bowel disease (IBD) appear to have a lower response to anti-tumour necrosis factor (TNF) therapy, with more frequent complications than younger patients. The objective of this study was to assess persistence on therapy and the safety of anti-TNF therapy in older patients (aged ≥ 60 years). METHODS: We retrospectively reviewed the database of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD), extracting data regarding IBD patients aged ≥ 60 years and controls < 60 years of age at their first course of anti-TNF treatment. Data concerning persistence on therapy over the first year of treatment (primary objective) together with data on reasons for treatment withdrawal, concomitant diseases and treatments were collected. RESULTS: We identified 114 anti-TNF-naϊve patients aged ≥ 60 years (median age 64 years, range 60-80 years; 47 males) compared with 330 younger controls aged < 60 years (median age 39 years, range 18-59 years; 57 males). Older patients with Crohn's disease (n = 73) showed a significantly lower persistence with every kind of anti-TNF therapy (whether analysed together [p < 0.001] or separately for intravenous and subcutaneous [SC] therapy) than younger controls, whereas older patients with ulcerative colitis (n = 41) showed a lower persistence when combining all kinds of anti-TNF treatment (p = 0.004) and for SC therapy. Secondary failures, infections, and neoplasias, but not primary failure, occurred more frequently in older IBD patients than in younger controls. CONCLUSION: Despite a comparable number of primary failures, older IBD patients treated for the first time with anti-TNF agents showed lower treatment persistence due to higher rates of secondary failure, adverse events, infections, and tumours than younger patients in the first year of follow-up. The reasons for this difference still remain unclear.

The Current Practice of Lynch Syndrome Diagnosis and Management in Italy: A Qualitative Assessment.

BACKGROUND: Lynch syndrome (LS) is the most frequent form of hereditary colorectal cancer (CRC; up to 3-5% of the total CRC burden) and predisposes to the development of other cancers. Multidisciplinary diagnostic strategies are relevant both to the index cases and to their at-risk relatives, but their implementation is still limited. Our study aimed to explore LS testing practices in Italy. METHODS: In order to ascertain the current practice of LS diagnosis and management, we conducted a qualitative assessment by sending a questionnaire to health care professionals at 4 Italian hospitals selected as "models" representing different hospital settings. Based on the surveys, we reconstructed the management pathways for CRC patients in terms of diagnostic strategies and health professionals involved. RESULTS: Seven of the 8 invited professionals filled in the questionnaire. Noncompliance with the latest guidelines was reported, as no tumor "screening" was performed on CRC cases. The lack of a structured multidisciplinary team who manages CRC patients from risk assessment to diagnosis and follow-up was reported. The availability of professionals and laboratory technologies differ widely between hospitals. As for cascade testing of at-risk relatives, a systematic and active approach was absent in all the considered hospitals. CONCLUSIONS: Our study shows that no structured and standardized pathways for the diagnosis and management of LS patients are currently in place in Italy. We envisage that by extending our research to further experiences and countries, an increasing awareness of the topic can be translated into a health gain for hereditary CRC patients and their at-risk relatives.

A Propensity Score-matched Comparison of Infliximab and Adalimumab in Tumour Necrosis Factor-α Inhibitor-naïve and Non-naïve Patients With Crohn's Disease: Real-Life Data From the Sicilian Network for Inflammatory Bowel Disease.

BACKGROUND AND AIMS: There is an unmet need to better understand the effectiveness of different biologics in inflammatory bowel diseases. We aimed at performing a multicentre, real-life comparison of the effectiveness of infliximab [IFX] and adalimumab [ADA] in Crohn's disease [CD]. METHODS: Data of consecutive patients with CD treated with IFX and ADA from January 2013 to May 2017 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. We used propensity score-matching accounting for the main baseline characteristics in TNF-α inhibitor-naïve and non-naïve patients. RESULTS: A total of 632 patients [735 total treatments] were included. Among naïve patients, a clinical benefit [the sum of steroid-free remission plus clinical response] was achieved in 81.8% patients treated with ADA and in 77.6% patients treated with IFX (adjusted odds ratio [OR]: 1.23, 95% CI 0.63-2-44, p = 0.547] at 12 weeks; after 1 year, a clinical benefit was achieved in 69.2% of patients treated with ADA and in 64.5% patients treated with IFX [adjusted OR: 1.10, 95% CI 0.61-1.96, p = 0.766]. Among non-naïve patients, a clinical benefit was achieved in 61.7% of patients treated with ADA and in 68.1% of patients treated with IFX [adjusted OR: 0.72, 95% CI 0.21-2.44, p = 0.600] at 12 weeks; after 1 year, a clinical benefit was achieved in 48.9% of patients treated with ADA and in 40.4% patients treated with IFX [adjusted OR: 1.23, 95% CI 0.54-2.86, p = 0.620]. CONCLUSIONS: In this propensity score-matched comparison of ADA and IFX in CD, both drugs showed high rates of clinical benefit, without significant differences between them.

LncRNA UCA1, Upregulated in CRC Biopsies and Downregulated in Serum Exosomes, Controls mRNA Expression by RNA-RNA Interactions.

Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) contribute to the onset of many neoplasias through RNA-RNA competitive interactions; in addition, they could be secreted by cancer cells into biological fluids, suggesting their potential diagnostic application. By analyzing the expression of 17 lncRNAs and 31 circRNAs in biopsies and serum exosomes from colorectal cancer (CRC) patients through qRT-PCR, we detected CCAT1, CCAT2, HOTAIR, and UCA1 upregulation and CDR1AS, MALAT1, and TUG1 downregulation in biopsies. In serum exosomes, UCA1 was downregulated, while circHIPK3 and TUG1 were upregulated. Combined receiver operating characteristic (ROC) curves of TUG1:UCA1 and circHIPK3:UCA1 showed high values of sensitivity and specificity. Through in vitro (i.e., RNA silencing and mitogen-activated protein kinase [MAPK] inhibition) and in silico analyses (i.e., expression correlation and RNA-RNA-binding prediction), we found that UCA1 could (1) be controlled by MAPKs through CEBPB; (2) sequester miR-135a, miR-143, miR-214, and miR-1271, protecting ANLN, BIRC5, IPO7, KIF2A, and KIF23 from microRNA (miRNA)-induced degradation; and (3) interact with mRNA 3'-UTRs, preventing miRNA binding. UCA1 and its co-regulated antisense LINC01764 could interact and reciprocally mask their own miRNA-binding sites. Functional enrichment analysis of the RNA-RNA network controlled by UCA1 suggested its potential involvement in cellular migration. The UCA1 regulatory axis would represent a promising target to develop innovative RNA-based therapeutics against CRC.

A real life comparison of the effectiveness of adalimumab and golimumab in moderate-to-severe ulcerative colitis, supported by propensity score analysis.

BACKGROUND: Adalimumab and golimumab are effective in the treatment of moderate to severe ulcerative colitis. AIMS: We reported the comparative effectiveness of adalimumab and golimumab in ulcerative colitis. METHODS: 118 patients treated with adalimumab and 79 treated with golimumab were included and evaluated at 8 weeks and at the end of follow up. RESULTS: Overall clinical benefit was 72.6% at 8 weeks and 58.9% at the end of follow up. Patients with longer disease duration and those treated with adalimumab had a better outcome. Clinical benefit was 78.8% in adalimumab patients and 63.3% in golimumab patients (p = 0.026) after 8 weeks; it was 66.9% in adalimumab patients and 46.8% in golimumab patients (p = 0.008) at the end of follow up. These data were confirmed by propensity score analysis. A further analysis considering adalimumab optimization as treatment failure showed that the difference between adalimumab and golimumab was not significant. CONCLUSION: Adalimumab and golimumab are effective in the treatment of ulcerative colitis. Adalimumab seems to be more effective than golimumab. This difference is probably affected by the impossibility of golimumab to be optimized in Italy while adalimumab is.

The real-world effectiveness of vedolizumab on intestinal and articular outcomes in inflammatory bowel diseases.

BACKGROUND: The effectiveness of vedolizumab in real-world practice is under evaluation, while its role in inflammatory bowel disease-associated spondyloarthritis is still unclear. AIMS: To report real-world data about the effectiveness of vedolizumab on intestinal and articular symptoms after 10 and 22 weeks of treatment. METHODS: Web-based data from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) were extracted to perform a prospective multicentre observational study. RESULTS: 163 patients (84 with Crohn's disease and 79 with ulcerative colitis) were included. At week 10, a steroid-free remission was achieved in 71 patients (43.6%), while at week 22 a steroid-free remission was obtained in 40.8% of patients. A response on articular symptoms was reported after 10 weeks of treatment in 17 out of 43 (39.5%) patients with active spondyloarthritis at baseline, and in 10 out of 22 (45.4%) patients at week 22. The only factor associated with articular response was the coexistence of clinical benefit on intestinal symptoms (at week 10: OR 8.471, p = 0.05; at week 22: OR 5.600, p = 0.08). CONCLUSIONS: Vedolizumab showed good effectiveness after 10 and 22 weeks of treatment. A subset of patients reported improvement also on articular symptoms, probably as a consequence of the concomitant control of gut inflammation.

Solitary hemangioma of the small intestine: an unusual cause of bleeding diagnosed at capsule endoscopy.

Solitary small intestine hemangiomas are rare and usually present with overt bleeding or chronic anemia. Diagnosis is usually difficult because traditional imaging techniques often lack accuracy. Capsule endoscopy is a new diagnostic tool that has showed greater sensitivity than other methods to reveal causes of bleeding in the small intestine. A case of hemangioma of the ileum in a 13-year-old boy is presented. Capsule endoscopy allowed diagnosis and planning of surgical treatment.

The role of capsule endoscopy in the work-up of obscure gastrointestinal bleeding.

OBJECTIVE: To evaluate the role of capsule endoscopy in the detection of causes of obscure gastrointestinal bleeding. METHODS: Fifteen patients, nine males and six females, mean age 46 years (range 20-75 years), were investigated. All patients had undergone upper and lower gastrointestinal endoscopy with no evidence of causes of bleeding. Indication for capsule endoscopy was overt bleeding in 10 patients (eight with melaena and two with rectal bleeding) and anaemia in five patients. RESULTS: Diagnosis was made in four out of 10 patients with overt bleeding (40%) and in four out of five (80%) in the group with anaemia. The overall detection rate was 53%. Of the eight patients with melaena, two had angiodysplasia, one showed a diffuse inflammation of the jejunum and ileum probably related to associated portal hypertension, and five had a normal examination. Of the two patients with rectal bleeding, one had a polyp in the terminal ileum and the other a normal examination. Of the five patients with anaemia, one had jejunal carcinoma, three had Crohn's disease and one had a normal endoscopy. CONCLUSION: Wireless capsule endoscopy is safe, effective, non-invasive, and provides definitive diagnosis in about one-half of patients presenting with obscure gastrointestinal bleeding and previous negative endoscopic examinations.