The Earlier You Find, the Better You Treat: Red Flags for Early Diagnosis of Inflammatory Bowel Disease.

Delayed diagnosis is a challenge in the management of inflammatory bowel disease (IBD). Several studies show a significant association between diagnostic delay and disease progression to complications and surgery, especially in Crohn's disease (CD). What risk factors are associated with diagnostic delay in IBD remains unclear. In order to reduce diagnostic delay, the Red Flags Index has been developed and validated. The combination of the Red Flags Index score and non-invasive biomarkers such as fecal calprotectin seems to be highly accurate in screening patients with underlying IBD to be referred for further diagnostic workup and eventual early effective treatment strategies. Our literature review aims to obtain a comprehensive overview of the impacts of diagnostic delay in IBD on the potential risk factors associated with IBD, how diagnostic tools may be effective in reducing diagnostic delay, and future perspectives in this field.

Real-world efficacy and safety of vedolizumab in managing ulcerative colitis versus Crohn's disease: results from an Italian multicenter study.

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

Comparison of Performances of Adalimumab Biosimilars SB5, ABP501, GP2017, and MSB11022 in Treating Patients with Inflammatory Bowel Diseases: A Real-Life, Multicenter, Observational Study.

BACKGROUND: Adalimumab (ADA) biosimilars have entered the therapeutic armamentarium of inflammatory bowel disease (IBD), allowing for the treatment of a greater number of patients for their reduced cost than the originator. However, comparative data on the efficacy and safety of the various ADA biosimilars remains scarce.We compare the efficacy and safety of ADA biosimilars SB5, ABP501, GP2017, and MSB11022 in treating IBD outpatients in a real-life Italian setting. METHODS: A retrospective analysis was performed on consecutive IBD outpatients with complete clinical, laboratory, and endoscopic data. Clinical activity was measured using the Mayo score in ulcerative colitis (UC) and the Harvey-Bradshaw Index in Crohn's disease (CD). The primary endpoints were the following: (1) induction of remission in patients new to biologics and patients new to ADA but previously exposed to other anti-tumor necrosis factor agents or other biologics; (2) maintenance of remission in patients switched from the ADA originator to an ADA biosimilar; and (3) safety of various biosimilars. RESULTS: A total of 533 patients were enrolled according to the inclusion criteria: 162 patients with UC and 371 patients with CD. Clinical remission was obtained in 79.6% of patients new to biologics and 59.2% of patients new to ADA but not to other biologics; clinical remission was maintained in 81.0% of patients switched from the originator, and adverse events were recorded in 6.7% of patients. There was no significant difference between the 4 ADA biosimilars for each predetermined endpoint. CONCLUSIONS: Adalimumab biosimilars are effective and safe in IBD treatment, both in new patients and in patients switched from the ADA originator. No difference in efficacy and safety was found between ADA biosimilars.

We treated 533 IBD patients with adalimumab (ADA) biosimilars SB5, APB501, GP2017, and MSB11022. No differences between these 4 ADA biosimilars were found for reaching remission in naive patients, maintaining remission for nonmedical switching, clinical response, steroid-free remission, surgery rate, mucosal healing, or safety.

Effectiveness of ustekinumab in patients with refractory Crohn's disease: a multicentre real-life study in Italy.

BACKGROUND: The effectiveness of ustekinumab in patients with refractory Crohn's disease (CD) has been investigated in several real-world studies. However, very few data concerning the real-life experience in Italy have been reported. Therefore, this study assessed the effectiveness of ustekinumab in a large cohort of Italian patients with refractory CD. METHODS: All patients who had started on ustekinumab after failure of or intolerance to antitumour necrosis factor-α (TNF-α) treatment at five tertiary centres between November 2018 and February 2020 were retrospectively enrolled. The coprimary outcome was corticosteroid-free clinical remission, defined as a Harvey-Bradshaw Index (HBI) score of ⩽4, at weeks 26 and 52. The secondary outcomes were changes in the HBI and C-reactive protein (CRP) values at weeks 8, 26, and 52 from baseline and the normalization of CRP in patients with initially abnormal values. RESULTS: Totally, 140 patients who had previously received at least one anti-TNF-α agent were enrolled; 40.0% received two anti-TNF-α agents and 20.0% received vedolizumab. At baseline, 108 patients (77.1%) had HBI scores of >4; of these, 56.5% and 58.3% achieved corticosteroid-free clinical remission at weeks 26 and 52, respectively. Significant decreases in HBI and CRP values were observed at weeks 8, 26, and 52 in the entire study cohort (all p < 0.0001). The CRP values were normalized in 34.9%, 37.8%, and 49.3% of the patients by weeks 8, 26, and 52, respectively. The baseline HBI score of ⩾8 was a negative predictor of corticosteroid-free clinical remission at week 52 (odds ratio: 0.21, 95% confidence interval: 0.08-0.56, p = 0.002). The probability of remaining on ustekinumab after 52 weeks was 92.1%. Eleven (7.9%) patients discontinued ustekinumab (three for adverse events). CONCLUSION: Our study findings confirm the effectiveness and safety of ustekinumab in patients with CD after failure of or intolerance to anti-TNF-α therapy.

Comparison of performances of infliximab biosimilars CT-P13 versus SB2 in the treatment of inflammatory bowel diseases: a real-life multicenter, observational study in Italy.

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

Long-term real-life efficacy and safety of infliximab and adalimumab in the treatment of inflammatory bowel diseases outpatients.

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

Infliximab biosimilar CT-P13 is effective and safe in treating inflammatory bowel diseases: a real-life multicenter, observational study in Italian primary inflammatory bowel disease centers.

BACKGROUND: The purpose of this study was to assess the efficacy and safety of biosimilar infliximab (IFX) CT-P13 in treating outpatients with inflammatory bowel disease (IBD) in Italian primary gastroenterology centers. METHODS: Consecutive IBD outpatients who completed the induction treatment were evaluated retrospectively. Clinical activity was scored according to the Mayo score for ulcerative colitis (UC) and to the Harvey-Bradshaw Index (HBI) for Crohn's disease (CD). The primary endpoint was the achievement of clinical remission (Mayo score ≤2 in UC and HBI ≤5 in CD). Secondary endpoints were clinical response to treatment, achievement of mucosal healing, and safety. RESULTS: One hundred forty-one patients (96 UC and 45 CD) were enrolled. Previous treatment with anti-tumor necrosis factor (TNF)α had been provided to 26% of UC patients and 28.9% of CD patients. Remission was achieved in 57.3% UC patients and in 75.6% CD patients during a median (interquartile range) follow up of 24 (6-24) months. Clinical response and mucosal healing were achieved in 87.5% and 75.0% of UC patients and in 84.4% and 84.2% of CD patients, respectively. By both univariate and multivariate analysis, age >40 years, presence of comorbidities, and naivety to anti-TNFα were significantly related to remission. Only one (0.7%) adverse event was reported in the CD group. Surgery was performed in 2.1% of UC patients and 6.7% of CD patients. Switching from IFX originator to biosimilar did not influence the maintenance of the clinical remission. CONCLUSION: This study confirmed the long-term efficacy and safety of CT-P13 therapy in IBD, in both naïve patients and those switching from IFX originator.

Vedolizumab is effective and safe in real-life treatment of inflammatory bowel diseases outpatients: A multicenter, observational study in primary inflammatory bowel disease centers.

BACKGROUND: Italian data currently available in managing ulcerative colitis (UC) and Crohn's disease (CD) patients with vedolizumab (VDZ) are coming just from secondary and tertiary centers. The present study aimed to assess the real-life efficacy and safety of VDZ to achieve remission in inflammatory bowel diseases (IBD) outpatients in primary gastroenterology centers. METHODS: Clinical activity was scored according to the Mayo score in UC and to the Harvey-Bradshaw Index (HBI) in CD. The primary endpoints were the achievement of clinical remission and safety. Secondary endpoints were clinical response to treatment, achievement of mucosal healing (MH), and steroid discontinuation. RESULTS: One hundred and thirty-six pts. were enrolled (91 UC and 45 CD pts). During an 18-month median follow-up, clinical remission was present in 63 (46.3%) pts.: in particular, it occurred in 48 (52.7%) patients in UC group and in 15 (33.3%) patients in CD group (p = 0.003). more in UC group. Fecal calprotectin ≥400 µg/g and presence of comorbidities were factors significantly related to the failure of remission in UC and CD, respectively. Ten (7.3%) cases of adverse events were recorded (2 required suspension of treatment). Clinical response was present in 105 (72.2%) pts.: 71 (78.0%) in UC and 34 (75.5%) in CD group. MH occurred in 47 (62.7%) UC and in 9 (50.0%) CD patients. Steroids discontinuation occurred in 92 (67.6%) pts.; 61 (67.0%) UC and 31 (68.9%) CD pts. CONCLUSION: VDZ is effective and safe in IBD outpatients, especially in UC patients.

Effectiveness and safety of adalimumab to treat outpatient ulcerative colitis: A real-life multicenter, observational study in primary inflammatory bowel disease centers.

Adalimumab (ADA) was approved in Italy for the treatment of ulcerative colitis (UC) unresponsive to standard treatments in 2014, but no data from real life are currently available. The aim of the present study was to assess the real-life efficacy and safety of ADA in managing UC outpatients in some Italian primary inflammatory bowel disease (IBD) centers after approval of ADA reimbursement.Consecutive UC outpatients with at least 3-month follow-up were retrospectively evaluated. The primary end point was the induction and maintenance of remission in UC, defined as Mayo score ≤2.One hundred seven patients were included. At 3-month follow-up, obtained in 102 (95.3%) patients, 56 (54.9%) patients achieved a clinical remission. At univariate analysis, both Mayo partial score >7 and Mayo subscore for endoscopy = 3 at entry showed to be significantly associated with the lack of remission induction.During a median (95% confidence interval [CI]) follow-up of 18 (12-24) months, 56.6% of patients were under clinical remission; clinical response was achieved in 89.2% of cases. Mucosal healing was achieved in 66 (76.7%) patients, and colectomy occurred in 3 (2.8%) patients. Both C-reactive protein and fecal calprotectin values significantly decreased during follow-up. Steroids discontinuation occurred in 67 (66.7%) patients, and ADA dose escalation was adopted in 9 (16.1%) patients under remission. No factor was significantly related to the maintenance of clinical remission.This first Italian experience found ADA safe and effective to induce and maintain remission in real-life UC outpatients.

Predictive value of the Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification on the outcome of diverticular disease of the colon: An international study.

BACKGROUND: Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification has been recently developed for patients suffering from diverticulosis and diverticular disease. AIMS: We assessed retrospectively the predictive value of DICA in patients for whom endoscopic data and clinical follow-up were available. METHODS: For each patient, we recorded: age, severity of DICA, presence of abdominal pain, C-reactive protein and faecal calprotectin test (if available) at the time of diagnosis; months of follow-up; therapy taken during the follow-up to maintain remission (if any); occurrence/recurrence of diverticulitis; need of surgery. RESULTS: We enrolled 1651 patients (793 M, 858 F, mean age 66.6 ± 11.1 years): 939 (56.9%) patients were classified as DICA 1, 501 (30.3%) patients as DICA 2 and 211 (12.8%) patients as DICA 3. The median follow-up was 24 (9-38) months. Acute diverticulitis (AD) occurred/recurred in 263 (15.9%) patients; surgery was necessary in 57 (21.7%) cases. DICA was the only factor significantly associated to the occurrence/recurrence of diverticulitis and surgery either at univariate (χ(2 )= 405.029; p < 0.0001) or multivariate analysis (hazard ratio = 4.319, 95% confidence interval (CI) 3.639-5.126; p < 0.0001). Only in DICA 2 patients was therapy effective for prevention of AD occurrence/recurrence with a hazard ratio (95% CI) of 0.598 (0.391-0.914) (p = 0.006, log rank test). Mesalazine-based therapies reduced the risk of AD occurrence/recurrence and needs of surgery with a hazard ratio (95% CI) of 0.2103 (0.122-0.364) and 0.459 (0.258-0.818), respectively. CONCLUSIONS: DICA classification is a valid parameter to predict the risk of diverticulitis occurrence/recurrence in patients suffering from diverticular disease of the colon.

Effectiveness of adalimumab for ambulatory ulcerative colitis patients after failure of infliximab treatment: a first "real-life" experience in primary gastroenterology centers in Italy.

BACKGROUND: Adalimumab (ADA) is the key treatment for ulcerative colitis (UC) unresponsive or intolerant to standard treatments. Our aim was to assess the efficacy and safety of ADA in treating ambulatory UC patients in primary gastroenterology centers. METHODS: Fifteen patients (6 male, median age 29.9 years, range 22.8-39.9 years) were enrolled. All were previously treated with infliximab (IFX). Clinical activity and endoscopic severity were scored according to the Crohn's disease activity index (CDAI) score and Mayo subscore for endoscopy, respectively. Patients were clinically assessed at weeks 4, 8, and thereafter at weeks 16, 24, 32, 40, 48, and 54. Colonoscopy was performed before starting treatment, at weeks 24 and 54. The co-primary endpoints were clinical remission at 24 and 54 weeks. The secondary endpoints included: 1) sustained clinical remission; 2) steroid-sparing effect; 3) mucosal healing; 4) need for colectomy. Induction dose of ADA was 160 mg at week 0, and then 80 mg at week 2, while ADA maintenance treatment was 40 mg every two weeks. RESULTS: Clinical remission was obtained in 11 (73.3%) and 15 (100%) patients at weeks 24 and 54 respectively. Ten patients (66.7%) were able to discontinue steroids and were under corticosteroid-free remission at week 54. No patients underwent to colectomy. Eight patients (53.33%) at week 24 and 9 patients (60%) at week 54 achieved complete mucosal healing (Mayo endoscopic score 0). Side effects were reported in 2 of 15 patients (13.3%); none of those patients stopped treatment. CONCLUSION: ADA seems to be effective and safe in UC outpatients affected by UC, and previously treated with IFX.

Managing ambulatory ulcerative colitis patients with infliximab: a long term follow-up study in primary gastroenterology centers.

BACKGROUND: Infliximab (IFX) is the key treatment for ulcerative colitis (UC) unresponsive to standard treatments. The aim of the present study was to assess the efficacy and safety of IFX in treating ambulatory UC patients in primary gastroenterology centers. METHODS: One hundred and eighteen patients (65 M, 63 F, median age 34 years, range 19-71 years), affected by UC, were treated with IFX. Clinical efficacy, safety, mucosal healing (MH), and histological healing (HH) were assessed at a scheduled follow-up of 42 months. RESULTS: Percentage of patients with clinical remission persistence at 42-month follow-up was 70.4%. Colectomy occurred in only 3 patients (2.7%). At 42-month follow-up percentage of patients with MH was 44.6%, and percentage of patients with HH was 24.3%. HH at 6-month follow-up occurred in 13 out of 34 patients (38.2%) with C-reactive protein (CRP) <3 and in 8 out of 76 patients (10.5%) with CRP ≥ 3 (p=0.002). Side effects were reported in 16 patients (13.6%): infusion reactions occurred in 7 patients, other severe side-effects occurred in 3 patients, and opportunistic infections occurred in 3 patients (2.5%). Finally, 3 cancers (2.5%) occurred during the follow-up period (1 breast, 1 kidney and 1 rectal cancer). Both univariate and multivariate analyses showed Hb <11.5 g/dL and HH at 6-month follow-up to be significantly associated with treatment failure during follow-up. CONCLUSIONS: IFX seems to be effective and safe in long-term treatment of outpatients affected by UC.

Effectiveness and safety of infliximab and adalimumab for ambulatory Crohn's disease patients in primary gastroenterology centres.

BACKGROUND: Infliximab (IFX) and adalimumab (ADA) are the key treatments for Crohn's Disease (CD), unresponsive to standard treatments. Our aim was to compare the efficacy and safety of IFX and ADA in treating CD in clinical practice. METHODS: One hundred and twenty-six patients (61 M, 65 F, mean age 36.2 years, range 19-67 years), affected by CD, were treated with infliximab (IFX, 59 patients) or adalimumab (ADA, 66 patients). Clinical efficacy, mucosal healing (MH), histological healing (HH), and safety were assessed. MH was defined complicated if healing of ulcers occurred with deformation of bowel profile and/or complete colonoscopy was impossible because of scars. RESULTS: Patients were followed-up for 36 months. No difference was found between IFX and ADA in maintaining long-term clinical remission, MH and HH. Complicated MH was present in 17 (28.8%) patients in IFX group and in 7 (10.6%) patients in ADA group (p=0.012). In 9 (15.2%) patients in IFX group and 2 (3.0%) patients in ADA group colonoscopy was incomplete without cecal intubation or terminal ileum exploration (p=0.024). Side effects were similar in both groups. CONCLUSIONS: Both IFX and ADA seem to be effective and safe in long-term outpatient treatment of CD in clinical practice.

Granulomatous interstitial nephritis in a patient with Crohn's disease.

A case of granulomatous interstitial nephritis (GIN) associated with Crohn's disease (CD) was reported. GIN is a rare pathological finding in renal biopsy specimens. In a patient affected by CD, granulomas may be found in various tissues and organs such as lymph nodes, mesentery, liver, and lungs and occasionally in bones, joints, and skeletal muscle. Few cases of granuloma have been reported in the kidney, and it is not always possible to relate the presence of granuloma to CD, to other interstitial granulomatosis diseases, or to a drug-induced reaction. The issue has a remarkable clinical effect; indeed, the answer requires a completely different therapeutic approach. The diagnosis analysis on the basis of clinical-pathological evidences and on reports from literature is discussed.

Obscure-occult bleeding: resolution of unexplained chronic sideropenic anaemia by colonoscopic removal of a colonic leiomyoma.

Although leiomyomas of the stomach or small intestine are relatively common, those of the colon or rectum are rare. Several cases of endoscopic resection of colorectal leiomyomas have been described. However, conventional polypectomy of leiomyomas can result in perforation. To reduce the risk of perforation, submucosal injection can be performed before removal. We report a case of chronic sideropenic anaemia in a patient affected by leiomyoma of the sigmoid colon in which after complete endoscopic enucleation of the lesion we obtained the stable resolution of anaemia.

Transcriptome profile of human colorectal adenomas.

Colorectal cancers are believed to arise predominantly from adenomas. Although these precancerous lesions have been subjected to extensive clinical, pathologic, and molecular analyses, little is currently known about the global gene expression changes accompanying their formation. To characterize the molecular processes underlying the transformation of normal colonic epithelium, we compared the transcriptomes of 32 prospectively collected adenomas with those of normal mucosa from the same individuals. Important differences emerged not only between the expression profiles of normal and adenomatous tissues but also between those of small and large adenomas. A key feature of the transformation process was the remodeling of the Wnt pathway reflected in patent overexpression and underexpression of 78 known components of this signaling cascade. The expression of 19 Wnt targets was closely correlated with clear up-regulation of KIAA1199, whose function is currently unknown. In normal mucosa, KIAA1199 expression was confined to cells in the lower portion of intestinal crypts, where Wnt signaling is physiologically active, but it was markedly increased in all adenomas, where it was expressed in most of the epithelial cells, and in colon cancer cell lines, it was markedly reduced by inactivation of the beta-catenin/T-cell factor(s) transcription complex, the pivotal mediator of Wnt signaling. Our transcriptomic profiles of normal colonic mucosa and colorectal adenomas shed new light on the early stages of colorectal tumorigenesis and identified KIAA1199 as a novel target of the Wnt signaling pathway and a putative marker of colorectal adenomatous transformation.