Impact of biological therapy in reducing the risk of arthritis development in inflammatory bowel diseases.

OBJECTIVE: Evaluate spondyloarthritis (SpA) incidence in inflammatory bowel diseases (IBD) between patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) and conventional DMARDs (cDMARDs) and define risk factors associated with SpA development. METHODS: Retrospective cohort study was conducted on patients with Crohn's disease (CD) or ulcerative colitis (UC) and divided into two cohorts: cDMARDs or bDMARDs/targeted synthetic (ts) DMARDs treated patients. Rheumatological assessment was performed in patients presenting musculoskeletal symptoms. Multivariate analysis and Kaplan-Meier curves were used to evaluate the adjusted SpA risk development. RESULTS: 507 patients were included in the study. 176 patients with CD received bDMARDs, 112 cDMARDs and 106 new SpA diagnosies were formulated. Females (OR 1.7 (95% CI 1.1 to 3), adjusted p=0.04), non-stricturing/non-penetrating phenotype (OR 2 (95% CI 1.1 to 3.4), adjusted p=0.01), psoriasis (OR 2.1 (95% CI 1 to 4.6), adjusted p=0.04) and non-infectious uveitis (OR 6.8 (95% CI 1.4 to 33.4), adjusted p=0.01) were associated with increased SpA risk development, while bDMARDs usage was protective (OR 0.4 (95% CI 0.2 to 0.8), adjusted p=0.01), statistically higher than cDMARDs throughout the entire follow-up (effect size 0.47). 98 patients with UC received b-tsDMARDs, 121 cDMARDs and 56 new SpA diagnoses were formulated. Females (OR 2.1 (95% CI 1 to 4.3), adjusted p=0.02) and psoriasis (OR 2.7 (95% CI 1 to 6.8), adjusted p=0.03) were associated with increased SpA risk development, while bDMARDs were protective for SpA development for up to 12 months of treatment compared with cDMARDs (p=0.03). CONCLUSIONS: bDMARDs treatment had an impact in reducing SpA development and clinical associated risk factors to transition from IBD to IBD-SpA emerged.

Transition care in patients with IBD: The pediatric and the adult gastroenterologist's perspective. Results from a national survey.

BACKGROUND: Transition is a crucial process in the care of IBD patients, although it remains largely heterogeneous. AIMS: To provide an overview of the transition process in Italy and to investigate the perspective of the paediatric and adult physicians. METHODS: An online survey was developed by the Italian Group for Inflammatory Bowel Diseases (IG-IBD) and the Italian Society of Paediatric Gastroenterology, Hepatology and Nutrition (SIGENP). RESULTS: 104 physicians (62 paediatric and 42 adult gastroenterologists) participated to the survey. The disease status was ranked with the highest priority among the key elements of the transition process. The age of the patient was perceived with a higher priority by paediatric gastroenterologists than by adult ones (p < 0.01). In most cases, the transition was organized through one or more joint meetings. Only less than 25 % of responders reported to involve other professions during transition. The struggle in leaving paediatric setting was perceived as the main obstacle to an effective transition process. Paediatric IBD gastroenterologists ranked the struggle in leaving the paediatric setting and the attending physician as higher critical point than adult gastroenterologists. CONCLUSIONS: The current survey provided a snapshot of the IBD transition process in Italy. The present findings highlight the need to embed transitional care in healthcare policy.

Current and Novel Uses of Intestinal Ultrasound in Inflammatory Bowel Disease.

Intestinal ultrasound (IUS) is a patient-centric, noninvasive, real-time, point-of-care tool with the capability to aid in diagnosis and monitoring of disease activity in both Crohn's disease and ulcerative colitis without the need for bowel preparation. IUS can be used as a tool for precision monitoring of inflammatory bowel disease (IBD) treatment response. IUS as a cross-sectional imaging tool is as accurate as magnetic resonance enterography (MRE) for assessing the ileum and is more accurate than MRE for colonic assessment proximal to the rectum. Multiple simple ultrasound-based scoring systems have been internally validated with endoscopy in both Crohn's disease and ulcerative colitis, and changes in IUS parameters can be seen as early as 2 weeks after treatment initiation. IUS also plays a unique role in IBD activity monitoring of patients in whom avoidance of invasive testing is paramount, such as children and pregnant patients. Novel uses go beyond monitoring activity, with potential use of elastography to measure bowel wall stiffness to detect fibrosis and bowel damage for enhanced decision-making. Ultimately, IUS is likely to expand in the United States, facilitated by accessible expert training, access to equipment, and the development of a reimbursement model. This article provides a comprehensive review of the current and novel uses of IUS in IBD.

Mucinous and Signet-Ring Cell Colonic Adenocarcinoma in Inflammatory Bowel Disease: A Case-Control Study.

A higher frequency of mucinous and signet-ring cell colonic adenocarcinoma has been reported in inflammatory bowel disease (IBD). The primary aim was to investigate the frequency of mucinous and signet-ring cell colorectal adenocarcinoma in patients with IBD (Cases) versus age-matched non-IBD Controls. The secondary aims were to compare the characteristics of these two histotypes of colorectal cancer (CRC) in IBD patients vs. Controls and to search for specific risk factors in IBD. In a case-control study, all IBD patients with CRC diagnosed from 2000 to 2022 were enrolled and matched for age (1:2) with non-IBD Controls with CRC. The study population included 120 CRC patients (40 IBD, 80 Controls). In IBD, CRC included standard adenocarcinoma in 23 (57.5%) patients mucinous/signet-ring cell adenocarcinoma in 17 (42.5%) patients. The proportion of mucinous/signet-ring cell adenocarcinoma was higher in IBD than in Controls (17 [42.5%] vs. 18 [22.5%]; p = 0.03). In rectal CRC, the proportion of mucinous/signet-ring cell adenocarcinoma was higher than standard adenocarcinoma in IBD (8 [47.1%] vs. 4 [17.4%]; p = 0.04) but not in Controls (4 [22.2%] vs. 20 [32.2%]; p = 0.59). In rectal CRC, the proportion of these two histotypes was higher in Cases than in Controls (8/12 [66.6%] vs. 4/24 [16.6%]; p = 0.008), with no risk factors identified in IBD. CRC was more frequently represented by mucinous/signet-ring cell adenocarcinoma in IBD than in age-matched non-IBD Controls. In IBD, these two CRC histotypes were more frequent in the rectum.

Niclosamide Enema for Active Distal Ulcerative Colitis: A Phase 1, Open-Label Study.

BACKGROUND: Oral and rectal formulations of 5-aminosalicylic acid are the first-line therapy for mild-to-moderate, distal ulcerative colitis (UC), but such a treatment is not effective in one-third of patients. Niclosamide is a small molecule, developed and approved as an orally administered drug to treat helminthic infections, with an excellent safety profile. Preclinical work showed that niclosamide is an anti-inflammatory agent, thereby providing the rationale to explore its safety and efficacy in patients with UC. This phase 1, open-label trial was aimed at assessing the safety of niclosamide formulated as an enema in patients with mild-to-moderate, distal UC, who relapsed on maintenance therapy with oral and/or rectal 5-aminosalicylic acid. METHODS: Seventeen patients with active UC received niclosamide enema (150 mg/60 mL) twice a day for 6 weeks. The primary endpoint was the safety of niclosamide treatment. Secondary endpoints included clinical remission and improvements in endoscopic Mayo/histologic scores. Endoscopic remission percentages exclude participants meeting criteria at baseline for endoscopic remission. RESULTS: Niclosamide was well tolerated by all 17 patients that were enrolled and treated. No serious adverse event was registered. Fifteen mild adverse events were registered in 6 patients and considered to be unrelated to the treatment. Clinical remission was achieved in 10 (59%) of 17 patients. Improvements of endoscopic Mayo score and histologic Geboes score were seen in 7 (58%) of 12 and 7 (41.2%) of 17 patients, respectively. CONCLUSIONS: Niclosamide enema treatment is safe and well tolerated. Niclosamide improves clinical symptoms and endoscopic/histologic signs of UC; however, appropriately designed placebo-controlled clinical trials are required to confirm efficacy.

Frequency and Predictors of Dysplasia in Pseudopolyp-like Colorectal Lesions in Patients with Long-Standing Inflammatory Bowel Disease.

Current endoscopic surveillance programs do not consider inflammatory bowel disease (IBD)-associated post-inflammatory polyps (pseudopolyps) per se clinically relevant, even though their presence seems to increase the risk of colorectal cancer (CRC). However, it remains unclear whether the link between pseudopolyps and CRC is indirect or whether some subsets of pseudopolyp-like lesions might eventually undergo neoplastic transformation. This study aimed to assess the frequency and predictors of dysplasia in pseudopolyp-like lesions in a population with long-standing colonic IBD. This was a retrospective, single-center study including patients with a colonic IBD (median disease duration of 192 months) and at least a pseudopolyp-like lesion biopsied or resected in the period from April 2021 to November 2022. One hundred and five pseudopolyps were identified in 105 patients (80 with ulcerative colitis and 25 with Crohn's disease). Twenty-three out of 105 pseudopolyp samples (22%) had dysplastic foci, and half of the dysplastic lesions were hyperplastic. Multivariate analysis showed that the age of the patients (odds ratio (OR) 1.1; p = 0.0012), size (OR 1.39; p = 0.0005), and right colonic location (OR 5.32; p = 0.04) were independent predictors of dysplasia, while previous exposure to immunosuppressors/biologics and left colonic location of the lesions were inversely correlated to dysplasia (OR 0.11; p = 0.005, and OR 0.09; p = 0.0008, respectively). No differences were seen between ulcerative colitis and Crohn's disease patients. Lesions with a size greater than 5 mm had a sensitivity of 87% and a specificity of 63% to be dysplastic. These data show that one-fourth of pseudopolyp-like lesions evident during surveillance colonoscopy in patients with longstanding IBD bear dysplastic foci and suggest treating such lesions properly.

Severe acute respiratory syndrome coronavirus 2 infection does not worsen the course of inflammatory bowel disease in the long term.

BACKGROUND: The long-term outcome of inflammatory bowel disease (IBD) patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is under investigation. AIM: To assess, in a prospective study, whether a recent SARS-CoV-2 infection increases the risk of IBD relapse within 12 months. METHODS: From March to April 2021, all IBD patients with recent (<2 months) SARS-CoV-2 infection (Cases) were enrolled. For each enrolled Case, four IBD Controls with no history of infection were considered. Clinical course of IBD was recorded for 12 months. Inclusion criteria: well defined diagnosis of IBD; age ≥18 and ≤85 years; 12-month follow-up; consent. Exclusion criteria: incomplete data; SARS-CoV-2 infection after enrollment. Additional inclusion criteria: recent SARS-CoV-2 infection for Cases; no history of SARS-CoV-2 infection for Controls. Data expressed as median [range]. Statistical analysis: Student-t-Test, Mann-Whitney U-test, χ2 test, multivariate logistic regression model [odds ratio (95% confidence interval)], Kaplan-Meier curves. RESULTS: One hundred forty-three IBD patients were enrolled. The analysis included 118 patients (22 met the exclusion criteria, three lost at follow-up): 29 (24.6%) Cases and 89 (75.4%) Controls. Demographic and clinical characteristics were comparable between groups. During the 12-month study, the frequency of IBD relapse was comparable between Cases and Controls [8 (27%) vs 19 (21%); P = 0.65]. At univariate analysis, SARS-CoV-2 infection was not a risk factor for IBD relapse within 12 months [1.5 (0.6-3.9); P = 0.34]. At multivariate analysis, IBD activity at baseline was the only risk factor for relapse [3.2 (1.1-9.1); P = 0.03]. Kaplan-Meier curves showed that survival from IBD relapse was comparable between Cases and Controls (P = 0.33). CONCLUSION: In a prospective 12-month study, a recent SARS-CoV-2 infection did not increase the risk of clinical relapse of IBD in the long term.

High Frequency of Deep Infiltrating Endometriosis in Patients with Inflammatory Bowel Disease: A Nested Case-Control Study.

INTRODUCTION: Inflammatory bowel disease (IBD) and endometriosis are chronic inflammatory diseases occurring in young women, sharing some clinical manifestations. In a multidisciplinary approach, we aimed to investigate symptoms, type, and site of pelvic endometriosis in IBD patients versus non-IBD controls with endometriosis. METHODS: In a prospective nested case-control study, all female premenopausal IBD patients showing symptoms compatible with endometriosis were enrolled. Patients were referred to dedicated gynecologists for assessing pelvic endometriosis by transvaginal sonography (TVS). Each IBD patient with endometriosis (cases) was retrospectively matched for age (±5 years) and body mass index (±1) with 4 patients with endometriosis at TVS but no-IBD (controls). Data were expressed as median [range]; the Mann-Whitney or Student t and χ2 tests were used for comparisons. RESULTS: Endometriosis was diagnosed in 25 (71%) out of 35 IBD patients with compatible symptoms including 12 (52.6%) Crohn's disease and 13 (47.4%) ulcerative colitis patients. Dyspareunia and dyschezia were significantly more frequent in cases versus controls (25 [73.7%] vs. 26 [45.6%]; p = 0.03). At TVS, deep infiltrating endometriosis (DIE) and posterior adenomyosis were significantly more frequently observed in cases versus controls (25 [100%] vs. 80 [80%]; p = 0.03 and 19 [76%] vs. 48 [48%]; p = 0.02). CONCLUSIONS: Endometriosis was detected in two-thirds of IBD patients with compatible symptoms. The frequency of DIE and posterior adenomyosis was higher in IBD than in controls. A diagnosis of endometriosis, often mimicking IBD activity, should be considered in subgroups of female patients with IBD.

Echopattern parameter as an aid to profile Crohn's disease patients.

BACKGROUND: Intestinal ultrasonography (US) allows for the characterization of the intestinal lesions and provides information on transmural inflammation. The aim of the study was to assess the clinical relevance of echopattern and correlation with Crohn's disease (CD) behavior and activity. METHODS: We performed a prospective study including CD patients assessed by intestinal US. The echopattern was classified as hypoechoic, hyperechoic and stratified. Color-doppler US was also performed in the thickest segment. RESULTS: One hundred CD patients were enrolled. The hypoechoic echopattern was significantly correlated with penetrating behavior (r = 0.44, p<0.0001), active disease (r = 0.21, p = 0.034), C-reactive protein/Fecal Calprotectin (r = 0.31, p = 0.004; r = 0.34, p = 0.031, respectively) and steroids (r = 0.33, p = 0.0008). Hypoechoic echopattern was associated with younger age than stratified (p = 0.046) and hyperechoic (p = 0.018) echopatterns. Bowel wall thickness was greater in the hypoechoic group than in the hyperechoic/stratified groups (p = 0.011 and p<0.0001, respectively). Hypoechoic echopattern was associated with fistulas (r = 0.52, p<0.0001) and increased vascularization (r = 0.32, p = 0.001). The hyperechoic echopattern showed a significant correlation with stricturing disease and an inverse correlation with fistulas. During a follow up period of 6 months, patients with hypoechoic echopattern had an increased risk of biological therapy need or surgery. CONCLUSIONS: The characterization of bowel wall echopattern allows for the identification of different CD behaviors.

Reversibility of Frail Phenotype in Patients with Inflammatory Bowel Diseases.

It was recently reported that frailty status can negatively influence the clinical course of patients with inflammatory bowel diseases (IBDs). Our recent study demonstrated that 20% of patients with an IBD are frail, and disease activity increases the risk of frailty. In the present study, we prospectively monitored this subgroup of frail patients, assessed whether the frailty status was reversible, and analyzed factors associated with frailty reversibility. Of the sixty-four frail patients with IBD enrolled, five (8%) were lost during the follow-up period and one (2%) underwent a colectomy. Eleven out of the fifty-eight (19%) patients maintained a frail phenotype during a median follow-up of 8 months (range 6-19 months), and thirty-five (60%) and twelve (21%) became pre-frail or fit, respectively. A comparison of the 58 patients at baseline and at the end of the study showed that frail phenotype reversibility occurred more frequently in patients who achieved clinical remission. A multivariate analysis showed that the improvement of the frail phenotype was inversely correlated with the persistence of clinically active disease (OR:0.1; 95% CI: 0.02-0.8) and a history of extra-intestinal manifestations (OR:0.1; 95% CI: 0.01-0.6) and positively correlated with the use of biologics (OR: 21.7; 95% CI: 3.4-263). Data indicate that the frail phenotype is a reversible condition in most IBD patients, and such a change relies on the improvement in disease activity.

Ultrasonographic Transmural Healing in Crohn's Disease.

Therapeutic targets in Crohn's disease (CD) have evolved greatly over the past several decades to include endoscopic improvement along with clinical remission. Yet CD is characterized by transmural damage, and there is increasing evidence of improved outcomes associated with transmural healing. Intestinal ultrasonography is a noninvasive, highly accurate imaging modality that provides real-time results and can assess for transmural healing in CD. In this review, we present the definition of transmural healing by ultrasonography, its comparison with other imaging modalities and with endoscopy, the efficacy of diverse therapies on achieving transmural healing, and data on patient outcomes in those achieving transmural healing. This review can guide clinicians who care for patients with inflammatory bowel disease on the added value of achieving transmural healing and its eventual incorporation as a target of therapy.

Frail Phenotype in Patients With Inflammatory Bowel Disease.

BACKGROUND: Recent retrospective studies have shown that frailty is common in hospitalized patients with inflammatory bowel disease (IBD) and enhances the risk of drug-related infections, postsurgery complications, hospital readmissions, and mortality, independently of age and comorbidities. We carried out a descriptive cohort study to evaluate the frequency of frail phenotype in IBD and analyzed the risk factors associated with this condition. METHODS: Frail phenotype was assessed in IBD patients by using the Fried frailty phenotype. Univariate and multivariate analyses were conducted to assess the risk factors for frail phenotype. Serum levels of interleukin (IL)-6 were quantified in patients with a frail or a fit phenotype by ELISA. RESULTS: Three hundred eighty-six IBD outpatients (198 Crohn's disease and 188 ulcerative colitis) were prospectively enrolled from December 2021 to April 2022. Frail phenotype was diagnosed in 64 of 386 (17%) IBD patients and was significantly associated with female gender, active disease, and current use of steroids. Multivariate analysis showed that active disease was a risk factor for frail phenotype (odds ratio, 11.5; 95% confidence interval, 3.9-33.9). No difference in IL-6 serum levels was seen between patients with a frail phenotype and those who were fit. CONCLUSIONS: This is the first prospective study showing that frail phenotype occurs in nearly one-fifth of IBD patients. Data indicate that active IBD is an independent risk factor for frail phenotype in IBD.

In IBD, frailty has been associated with enhanced risk of adverse outcomes. In this prospective study, nearly one-fifth of IBD patients were frail, and active disease was an independent risk factor for the frail phenotype.

Hidradenitis suppurativa and inflammatory bowel disease in a nested case-control study.

BACKGROUND: Association between Hidradenitis Suppurativa (HS) and Inflammatory Bowel Disease (IBD) has been suggested. AIMS: To assess characteristics of HS and IBD in patients with or without concomitant IBD. METHODS: In a prospective, nested case-control study, each IBD patient with concomitant HS (Case) was retrospectively matched with 4 patients with HS and no IBD (Controls) for gender and age (±5 years).HS was classified according to the Hurley score and the International Hidradenitis Suppurativa Severity Score System (IHS4). Data were expressed as mean (Standard Deviation). Statistical analysis included Student-t Test or Mann-Whitney Test, χ2 test, univariate and multivariate logistic regression. RESULTS: The study population included 125 patients with HS: 25 with IBD, 100 matched Controls with no IBD. IBD group included 19 (76%) Crohn's disease and 6 (24%) Ulcerative Colitis patients. Obesity, familial HS and perianal HS were less frequent in Cases than in Controls (1[4%] vs 25(25%];p = 0.02; 1[4%] vs 21(21%];p = 0.04; 1[4%] vs 31(31%];p = 0.005, respectively).HS was less severe in Cases when assessed by the IHS4 (5.9 ± 4 vs 9 ± 6.7;p = 0.04).Complete drug-induced response for HS was more frequent in IBD (13[53%] vs28 (28%]; p = 0.04). CONCLUSION: Clinical characteristics of HS and of patients differed between Cases and Controls. Present findings suggest the need to appropriately search and assess skin lesions compatible with HS in IBD.

Endoscopic Predictors of Neoplastic Lesions in Inflammatory Bowel Diseases Patients Undergoing Chromoendoscopy.

Dye-based chromoendoscopy (DCE) with targeted biopsies is recommended for surveillance of patients with long-standing inflammatory bowel diseases (IBD), but endoscopic features that predict dysplasia are not fully clarified. We here aimed at identifying predictive factors of dysplastic/neoplastic lesions in IBD patients undergoing DCE. Two-hundred-and-nineteen patients were consecutively and prospectively enrolled from October 2019 to March 2022. One-hundred-and-forty-five out of 219 patients underwent DCE, and 148 lesions were detected in 79/145 (54%) patients. Thirty-nine lesions (26%) were dysplastic and one of them contained a CRC. Among these lesions, 7 (17.9%) had Kudo pit pattern I-II and 32 (82.1%) had a neoplastic pit pattern (Kudo III-IV). Multivariate analysis showed that neoplastic lesions Kudo III-IV (OR: 5.8, 95% CI: 2.3−14.6; p = 0.0002), lesion's size (OR 1.16, 95% CI: 1.06−1.26; p = 0.0009), and polypoid lesions according to Paris Classification (OR 7.4, 95% CI: 2.7−20.2; p = 0.0001) were independent predictors of dysplasia. A cut-off of lesion's size > 7 mm was identified as the best predictor of dysplasia. Among such features, Kudo pit pattern III-IV had the highest sensitivity and specificity to predict dysplasia (79% and 80%, respectively). Lesions with all three endoscopic features had a sensitivity of 90% and specificity of 100% to predict dysplasia. In contrast, non-polypoid lesions were inversely associated with dysplasia (OR 0.13, 95% CI: 0.05−0.36; p = 0.0001). These findings indicate that, in IBD patients, DCE-evidenced polypoid lesions with Kudo pit pattern III-IV and size > 7 mm are frequently dysplastic.

Long-Term Risk of Colectomy in Patients with Severe Ulcerative Colitis Responding to Intravenous Corticosteroids or Infliximab.

Background and aims: Intravenous corticosteroids (IVCS) and rescue therapy with infliximab (IFX) are useful for managing patients with acute severe ulcerative colitis (ASUC). However, nearly one fifth of responders undergo colectomy. Predictive factors of colectomy in this subset of patients are not fully known. We retrospectively examined the long-term risk and the predictors of colectomy in ASUC patients achieving clinical remission following treatment with IVCS or IFX. Patients and methods: Clinical and demographic characteristics were evaluated in consecutive ASUC patients who were admitted to the "Tor Vergata University" hospital between 2010 and 2020 and responded to IVCS or IFX. A multivariate logistic regression model was constructed to identify independent predictors of colectomy. Results: A total of 116 ASUC patients responding to IVCS (98 patients) or IFX (18 patients) were followed up for a median of 46 months. After discharge, 29 patients (25%) underwent colectomy. Multivariate analysis showed that a serum albumin level <3 g/dL and colonic dilation >5.5 cm on admission were independent predictors of colectomy (OR: 6.9, 95% CI: 2.08−22.8, and OR 8.5, 95% CI: 1.23−58.3, respectively). Patients with both these factors had a risk of colectomy 13 times greater than those with no risk factor. Conclusions: A low serum albumin level and colonic dilation are risk factors of long-term colectomy in ASUC patients responding to IVCS or IFX.

Ultrasonography Tight Control and Monitoring in Crohn's Disease During Different Biological Therapies: A Multicenter Study.

BACKGROUND & AIMS: Bowel ultrasonography (BUS) is a noninvasive tool for evaluating bowel activity in Crohn's disease (CD) patients. Aim of our multicenter study was to assess whether BUS helps to monitor intestinal activity improvement/resolution following different biological therapies. METHODS: Adult CD patients were prospectively enrolled at 16 sites in Italy. Changes in BUS parameters [i.e. bowel wall thickening (BWT), lesion length, echo pattern, blood flow changes and transmural healing (TH: normalization of all BUS parameters)] were analyzed at baseline and after 3, 6 and 12 months of different biological therapies. RESULTS: One hundred eighty-eight out of 201 CD patients were enrolled and analyzed (116 males [62%]; median age 36 years). Fifty-five percent of patients were treated with adalimumab, 16% with infliximab, 13% with vedolizumab and 16% with ustekinumab. TH rates at 12 months were 27.5% with an NNT of 3.6. TH at 12 months after adalimumab was 26.8%, 37% after infliximab, 27.2% after vedolizumab and 20% after ustekinumab. Mean BWT improvement from baseline was statistically significant at 3 and 12 months (P < .0001). Median Harvey-Bradshaw index, C-reactive protein and fecal calprotectin decreased after 12 months from baseline (P < .0001). Logistic regression analysis showed colonic lesion was associated with a higher risk of TH at 3 months and a greater BWT at baseline was associated with a lower risk of TH at 3 months [P = .03 (OR 0.70, 95% CI 0.50-0.97)] and 12 months [P = .01 (OR 0.58, 95% CI 0.38-0.89)]. At 3 months therapy optimization during the study was the only independent factor associated with a higher risk of no ultrasonographic response [P = .02 (OR 3.34, 95% CI 1.18-9.47)] and at 12 months disease duration [P = .02 (OR 3.03, 95% CI 1.15-7.94)]. CONCLUSIONS: Data indicate that BUS is useful to monitor biologics-induced bowel activity improvement/resolution in CD.

Long-Term Outcomes and Predictive Factors of Hospitalized Patients with Severe Ulcerative Colitis Treated with Intravenous Corticosteroids.

Background and Aims: Treatment with intravenous corticosteroids (IVCS) is a mainstay in the management of acute severe ulcerative colitis (UC). Although most patients respond to IVCS, little is known about the long-term outcomes. In this study, we assessed the long-term outcomes of IVCS in a real-life cohort. Methods: Disease activity, clinical relapse (partial Mayo score >4), the need for steroids or other maintenance therapies and the rates of colectomy and re-hospitalization were evaluated in consecutive patients admitted to the Tor Vergata University hospital between 2010 and 2020 for acute severe UC who responded to IVCS. Results: Eighty-eight patients were followed up with for a median period of 46 (range 6-133) months. Of these, 56 (64%) patients were treated with 5-aminosalycilic acid and 32 (36%) with immunomodulators or biologics after discharge. A total of 60 out of 88 patients (68%) relapsed, 28 (32%) were re-hospitalized, and 15 (17%) underwent a colectomy with no difference between the two maintenance therapy groups. The multivariate analysis showed that patients in clinical remission 6 months after discharge had a lower risk of relapse during the follow-up. Conclusions: Nearly two-thirds of patients with acute UC responding to IVCS experienced relapse after a median follow-up of 4 years, and this was not influenced by the maintenance therapy.

Efficacy and tolerability of very low-volume bowel preparation in patients with inflammatory bowel diseases.

OBJECTIVES: An adequate bowel preparation is essential for a quality colonoscopy. Patients with inflammatory bowel disease (IBD) show low compliance with bowel preparation due to the large volume of lavage solution to be ingested, especially if active symptoms are present, and the frequency of having a colonoscopy. We evaluated the efficacy and tolerability of a very low-volume (VLV) polyethylene glycol (PEG)-based solution in patients with IBD. METHODS: A cohort of 103 consecutive patients, 56 with Crohn's disease and 47 with ulcerative colitis, received a 1-L PEG-based bowel preparation divided into two 500-mL doses taken the evening before and the morning of the colonoscopy, each dose followed by at least another 500-mL of clear fluids. Colon cleansing was scored according to the Boston Bowel Preparation Scale (BBPS) and evaluated in relation to influencing variables. RESULTS: Bowel cleansing was adequate (BBPS ≥ 6) in 88 patients (85.4%). The time interval between the end of bowel preparation and the beginning of colonoscopy and the disease activity significantly affected colon cleansing. Most patients declared a complete intake of lavage solution (99%), the willingness to repeat the same bowel preparation in a future colonoscopy (86.4%), and a good taste assessment. CONCLUSION: The VLV PEG-based bowel preparation is effective and well accepted by IBD patients. As minimizing the volume of lavage solution required, the VLV-bowel preparation here tested could be of choice in subjects who perform periodically colonoscopy or in those who do not tolerate a larger amount of liquids.

A Pharmacological Batch of Mongersen that Downregulates Smad7 is Effective as Induction Therapy in Active Crohn's Disease: A Phase II, Open-Label Study.

BACKGROUND: A recent phase III trial did not confirm the previous clinical and endoscopic improvements seen in patients with Crohn's disease (CD) receiving Mongersen, an oral Smad7 antisense oligonucleotide. Factors accounting for such a discrepancy are unknown. OBJECTIVE: Our objective was to further assess whether Mongersen was effective as induction therapy in active CD and evaluate the in vitro inhibitory effect of various batches of Mongersen used in the previous and present trials on Smad7 expression. METHODS: In a phase II, open-label study, 18 patients with active CD (Crohn's Disease Activity Index [CDAI] score > 220 and evidence of endoscopic lesions) received Mongersen 160 mg/day for 12 weeks. The rates of clinical remission, defined as CDAI < 150, and clinical response, defined as a CDAI score decrease ≥ 100, were evaluated at week 4, 8, and 12. The fraction of circulating CCR9-expressing leukocytes was assessed by flow cytometry. Smad7 expression was evaluated in the human colorectal cancer cell line HCT-116 transfected with different batches of Mongersen using real-time polymerase chain reaction (PCR) and Western blotting, RESULTS: The proportions of patients experiencing clinical remission were 38.9%, 55.6%, and 50.0% at week 4, 8, and 12, respectively. At the same time points, the rates of clinical response were 72.2%, 77.8%, and 77.8%, respectively. Mongersen reduced the percentages of CCR9-expressing CD45+ cells. The batch of Mongersen used in this study, but not two batches used in the phase III study, inhibited Smad7 expression in HCT-116 cells. CONCLUSIONS: The present findings support the clinical benefit of Mongersen in active CD and show that various batches manufactured during the GED0301 program differ in their ability to inhibit in vitro Smad7. TRIAL REGISTRATION NUMBER: NCT02685683; EudraCT 2015-001693-18.