Real-life efficacy and safety of Ustekinumab as second- or third-line therapy in Crohn's disease: results from a large Italian cohort study.

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

General practitioners' management of symptomatic uncomplicated diverticular disease of the colon by using rifaximin, a non-adsorbable antibiotic.

OBJECTIVE: Symptomatic uncomplicated diverticular disease of the colon (SUDD) is generally managed by gastroenterologists rather than General Practitioners (GPs). The aim of this study was to assess the efficacy of the treatment of SUDD with rifaximin, a non-absorbable antibiotic, in a primary care setting by GPs. PATIENTS AND METHODS: This retrospective, observational study investigated the use of rifaximin at a dose of 400 mg b.i.d. for 5, 7 or 10 days monthly, up to 3 months. The symptoms were reported by the patients using a visual analogic scale (VAS) of 0-10. RESULTS: 286 SUDD patients were enrolled (44.4% of men, average age 70.92±10.98). Respectively, 15 (5.2%) patients received the treatment for 5 days, 205 (71.7%) for 7 days and 66 (23.1%) for 10 days. After three months, a significant reduction of VAS score was observed in almost all symptoms assessed: 135 (47.2%) patients reported no abdominal pain (p<0.001) and 23 (8.1%) reported no symptom. Adverse events related to the treatment were recorded in 3 (1.04%) patients, all of them mild and not requiring interruption of the treatment. Acute diverticulitis occurred in 9 (3.1%) patients, but only 2 of them [0.7% (n=2)] underwent surgery due to complicated diverticulitis. Analysis within the different treatment groups (5, 7 and 10 days) shows that rifaximin treatment is effective in reducing the severity of symptoms in almost all groups except for the constipation in the 5-day group. CONCLUSIONS: Rifaximin can be effectively used by GPs in real-life for the management of SUDD.

Comparison of the effectiveness of infliximab and adalimumab in preventing postoperative recurrence in patients with Crohn's disease: an open-label, pilot study.

BACKGROUND: Endoscopic and clinical recurrence of Crohn's disease (CD) appears in up to 80 and 30 % of patients, respectively, 1 year after surgery. Both infliximab (IFX) and adalimumab (ADA) have been demonstrated to be effective in reducing the possibility of recurrence after surgery, but head-to-head studies have not been performed so far. The aim of this open-label prospective study was to compare endoscopic, histological and clinical recurrence after 1 year of treatment with IFX or ADA as postoperative prophylaxis in CD patients with a high risk of recurrence. METHODS: Consecutive CD patients who underwent curative ileocolonic resection were randomized to receive IFX or ADA for 1 year. Co-primary endpoints were endoscopic, histological and clinical recurrence after 12 months of therapy. RESULTS: Twenty consecutive CD patients (9 males and 11 females; median age 32.5 years, range 20-39 years) were enrolled after undergoing curative ileocolonic resection. Among the 10 patients treated with IFX, 2 (20 %) had endoscopic recurrence compared to 1 (10 %) in the group of 10 ADA patients (p = 1.0). Three out of 10 (30 %) IFX patients and 2 out of 10 (20 %) ADA patients had histological recurrence (p = 1.0). No significant clinical differences were found between the two groups. CONCLUSIONS: IFX and ADA were similar in preventing histological, endoscopic and clinical recurrence after curative ileocolonic resection in high risk CD patients.

Expression of basic fibroblastic growth factor, syndecan 1 and tumour necrosis factor α in resected acute colonic diverticulitis.

AIM: Inflammation and fibrosis are present in both colonic diverticulitis and Crohn's disease (CD). The molecular pattern of basic fibroblastic growth factor (bFGF) and syndecan 1 (SD1) expression is altered in stenosing CD, but their expression in resected complicated colonic diverticulitis (ACD) is unknown. METHOD: The expression of bFGF, SD1 and tumour necrosis factor α (TNF-α) in 20 patients after resection of ACD was compared with 15 patients having a resection for CD. Analysis was conducted using real-time reverse transcriptase polymerase chain reaction in biopsy samples. RESULTS: Lymphocytic and neutrophil inflammation scores were similar in both groups (P = 0.771 and P = 0.562). TNF-α and bFGF expression was significantly higher in ACD than in CD (P < 0.0001 and P = 0.009). SD1 expression was similar in both groups (P = 0.841). CONCLUSION: TNF-α and bFGF are significantly overexpressed in ACD with respect to CD, whilst SD1 levels do not differ. The findings confirm that inflammation and its association with altered molecular patterns of mucosal healing may play an important role in the phenotype of the diseases.

Intermittent versus every-day mesalazine therapy in preventing complications of diverticular disease: a long-term follow-up study.

BACKGROUND: Mesalazine seems to be effective in preventing recurrence of acute uncomplicated diverticulitis (AUD), but the optimal mesalazine scheme to achieve these results is still debated. AIM: To assess the effectiveness of two different mesalazine-based treatments in preventing recurrence of AUD and the occurrence of other complications of diverticular disease (DD) during a long-term follow-up. PATIENTS AND METHODS: We reviewed 311 patients suffer from recent episode of AUD and undergoing to mesalazine treatment: 207 (group A, 105 males, median age 63 years, range 47-74 years) were treated with mesalazine 1.6 g for 10 days each month, whilst 104 (group B, 55 males, median age 65 years, range 50-72 years) were treated with mesalazine 1.6 g every day. Patients were followed-up every 6 months (median 7.5 months, range 5-13 months). RESULTS: Patients were followed-up for a mean time of 3 years (range 12-72 months). Overall, occurrence of complication recurred more frequently in group A than in group B (p = 0.030, log-rank test). Acute diverticulitis recurred in 17 (8.2%) patients in group A and in 3 (2.9%) in group B; diverticular bleeding occurred in 4 (1.9%) patients in group A and in 1 (0.96%) patient in group B; surgery was required in 3 (1.4%) patients in group A and in no (0%) patient in group B. CONCLUSIONS: This is the first study showing that long-term mesalazine treatment is significantly better that intermittent mesalazine treatment in preventing occurrence of DD complications after an attack of acute diverticulitis.

Mucosal expression of basic fibroblastic growth factor, Syndecan 1 and tumor necrosis factor-alpha in diverticular disease of the colon: a case-control study.

BACKGROUND: Inflammation may be detected in diverticular disease (DD), and fibrosis may also develop. We assessed the mucosal expression of bFGF, SD1, and TNF-α in DD according to the severity of the disease. Moreover, we assessed the response to therapy of these cytokines in acute uncomplicated diverticulitis (AUD). METHODS: Fifteen patients affected by AUD and seven patients affected by symptomatic uncomplicated diverticular disease (SUDD) were enrolled. Patients with asymptomatic diverticulosis (AD), segmental colitis associated with diverticulosis (SCAD), ulcerative colitis (UC), and healthy subjects (HC) served as control groups. KEY RESULTS: The expression of bFGF, SD1, and TNF-α was significantly higher in diverticulitis than in healthy controls, in diverticulosis, and in uncomplicated diverticular disease. Cytokines were significantly higher in uncomplicated diverticular disease than in healthy controls. Cytokine expression in diverticulitis did not differ significantly from that of ulcerative colitis. After treatment, TNF-α expression dropped significantly. CONCLUSIONS & INFERENCES: Mucosal TNF-α is overexpressed only in symptomatic DD, while SD1 and bFGF are already overexpressed in AD. Finally, TNF-α but not SD1 or bFGF expression seems to be influenced by the treatment in AUD.

Musosal tumour necrosis factor α in diverticular disease of the colon is overexpressed with disease severity.

AIM: Inflammation occurs in diverticular disease (DD), but there is little information on inflammatory cytokines such as tumour necrosis factor α (TNF-α). The aim of this study was to assess TNF-α expression in DD and to see whether it is related to the severity of the disease. METHOD: Twenty-four patients with symptomatic DD were divided into those with acute uncomplicated diverticulitis (AUD) (12 patients) and those with symptomatic uncomplicated diverticular disease (SUDD) (12 patients). Twelve further patients with asymptomatic diverticulosis (AD), six with segmental colitis associated with diverticulosis (SCAD), with ulcerative colitis (UC) and six healthy individuals (HC) were enrolled as controls. TNF-α expression in the colonic mucosa was assessed by the amount of mRNA codifying for the synthesis of TNF-α. RESULTS: TNF-α expression was significantly higher in AUD than in HC (P=0.0007), in AD (P=0.0001) and in SUDD (P=0.0179). It was significantly higher also in SUDD than in HC (P=0.0007) and in AD (P=0.0001). TNF-α expression in AUD did not differ significantly from that in UC (P=0.0678) and SCAD (P=0.0610). It was significantly higher in UC, SCAD and AUD than in SUDD (P=0.0007, P=0.0001, P=0.0179). CONCLUSION: TNF-α expression in DD seems to be related to the severity of the disease. In particular, it appears to be overexpressed in DD with inflammation (AUD and SUDD) compared with DD without (AD).

Role of fecal calprotectin in the diagnosis and treatment of segmental colitis associated with diverticulosis.

AIM: Information about fecal calprotectin (FC) in segmental colitis associated with diverticulosis (SCAD) is lacking. We assessed FC in SCAD, comparing it healthy controls (HC), irritable bowel syndrome (IBS), diverticular disease (DD), ulcerative colitis (UC). Moreover, we compared FC levels in different degrees of SCAD and assessed FC SCAD before and after treatment. METHODS: Twenty-seven consecutive patients with a new endoscopic diagnosis of SCAD, and 16 patients for each control group, underwent to FC assessment. FC was assessed by semi-quantitative method. RESULTS: FC was not increased in HC and in IBS patients, whilst it was increased in DD, SCAD, and UC. FC concentration was higher in SCAD and UC than in DD (SCAD vs. DD, P=0.05). No difference was found in FC concentration between SCAD and UC (P=0.213), as well as between different degree of SCAD (P= 0.178). After treatment, FC values decreased to normal values in all patients obtaining remission (P<0.0005). Three patients experienced still symptoms (one SCAD type B and two SCAD type D patients), and in all of them FC was still detectable. CONCLUSION: FC may be useful in differentiating SCAD from functional syndromes. Moreover, it may be useful in assessing response to therapy.

Inflammatory manifestations at colonoscopy in patients with colonic diverticular disease.

BACKGROUND: Ulcerative colitis with diverticulosis (UCD), segmental colitis associated with diverticulosis (SCAD) and acute uncomplicated diverticulitis (AUD) may affect the same colonic regions, but the real incidence of these entities in clinical practice is unknown. AIM: To assess the incidence and the endoscopic findings of UCD, SCAD and AUD. METHODS: From January 2004 to June 2009, 8525 consecutive colonoscopies were performed. Diagnosis of the diseases was based on specific endoscopic and histological (UCD and SCAD), and on endoscopic and radiological (AUD) patterns. RESULTS: Ulcerative colitis with diverticulosis was diagnosed in 25 patients (0.3%), SCAD was diagnosed in 129 patients (2%) and AUD was diagnosed in 130 patients (2%). In UCD, the inflammation in colonic area harbouring diverticula always affects the overall colonic mucosa in all cases, involving also diverticular orifices. The endoscopic characteristic of SCAD is that inflammation is mainly detected within the inter-diverticular mucosa without involvement of the diverticular orifices. In AUD, the inflammation affects primarily diverticular orifice and peri-diverticular mucosa. CONCLUSIONS: In clinical practice, the incidence of mucosal inflammation in the presence of colonic diverticular disease is low and endoscopy is the mainstay of differential diagnosis.

Safety and effectiveness of infliximab for inflammatory bowel diseases in clinical practice.

BACKGROUND AND OBJECTIVES: Our aim was to assess the efficacy and safety of infliximab (IFX) in clinical practice in three Primary Care, Hospital Centers. MATERIAL AND METHODS: From September 2004 to December 2008 62 patients (28 males, 34 females, mean age 30.25 years, range 15-55 years), affected by ulcerative colitis (UC) (23 pts) or by Crohn's disease (CD) (39 patients) were treated. Clinical efficacy, safety, mucosal healing and quality of life were assessed both in UC and CD. RESULTS: A total of 746 infusions were performed. IFX was administered for a mean of 26 months (range 8-44 months). 33/39 (84.61%) pts with CD were in remission under treatment with IFX for a mean time of 19 months (range 12-44 months). Mean Crohn Disease Activity Index (CDAI) score decreased from 295 (range 258-346) to 136 (range 98-136) (p < 0.005). Inflammatory Bowel Disease Quality of Life (IBDQL) improved from 48 (at entry) to 198 (at the end of the study) (p < 0.005). 20/23 (86.95%) patients with UC were in remission under treatment with IFX for a mean of 18 months (range 8-34 months). Mean Disease Activity Index (DAI) decreased from 11 (range 9-12) to < 3 (range 2-3) (p < 0.05). Mean Mayo Subscore for Endoscopy decreased from 3 to < 1 (range 0-1). IBDQL improved from 56 (at entry) to 194 (at the end of the study) (p < 0.005). Only 5 patients (8.06%) experienced side-effects. CONCLUSIONS: Long-term outpatients treatment with IFX seems to be safe and effective in managing patients affected by IBD in clinical practice.

The endoscopic spectrum of segmental colitis associated with diverticulosis.

OBJECTIVE: An endoscopic classification of 'Segmental colitis associated with diverticulosis' (SCAD) is lacking. Our aim was therefore to assess the endoscopic spectrum of SCAD, comparing it with the histological and clinical features. METHOD: A prospective study was performed from January 2004 to October 2007. Diagnosis of SCAD was made on the basis of specific endoscopic and histological patterns. RESULTS: A total of 6230 consecutive colonoscopies were performed during the study period. SCAD was diagnosed in 92 (1.48%) patients, with four endoscopic patterns: pattern A, 'crescentic fold disease' (52.20%); pattern B, 'Mild-to moderate ulcerative colitis-like' pattern (30.40%); pattern C, 'Crohn's disease colitis-like' pattern (10.90%); pattern D, 'Severe ulcerative colitis-like' pattern (6.50%). Most patients with patterns A (58.33%, P < 0.018) and B (89.29%, P < 0.00001) showed histological alterations resembling moderate ulcerative colitis (UC). In pattern C, larger histological variability was found (P < 0.01). All patients showing pattern D showed the typical histological alteration changes of severe UC (P < 0.0001). In pattern A (60.42%, P = n.s.) and pattern B (46.43%, P = n.s.), diarrhoea was the most common symptom whilst abdominal pain was the most frequent in pattern C (50%, P = n.s.) and pattern D (83.33%, P = n.s.) patients. CONCLUSIONS: Endoscopic patterns of SCAD may range from mild to severe inflammation. The histopathological findings but not clinical features showed a statistically significant association with the degree of endoscopic severity.

Review article: the current and evolving treatment of colonic diverticular disease.

BACKGROUND: Formation of colonic diverticula, via herniation of the colonic wall, is responsible for the development of diverticulosis and consequently diverticular disease. Diverticular disease can be associated with numerous debilitating abdominal and gastrointestinal symptoms (including pain, bloating, nausea, constipation and diarrhoea). AIMS: To review the state of treatment for diverticular disease and its complications, and briefly discuss potential future therapies. METHODS: PubMed and recent conference abstracts were searched for articles describing the treatment of diverticular disease. RESULTS: Many physicians will recommend alterations to lifestyle and increasing fibre consumption. Empirical antibiotics remain the mainstay of therapy for patients with diverticular disease and rifaximin seems to be the best choice. In severe or relapsing disease, surgical intervention is often the only remaining treatment option. Although novel treatment options are yet to become available, the addition of therapies based on mesalazine (mesalamine) and probiotics may enhance treatment efficacy. CONCLUSIONS: Data suggest that diverticular disease may share many of the hallmarks of other, better-characterized inflammatory bowel diseases; however, treatment options for patients with diverticular disease are scarce, revolving around antibiotic treatment and surgery. There is a need for a better understanding of the fundamental mechanisms of diverticular disease to design treatment regimens accordingly.

Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference.

BACKGROUND: Breath tests represent a valid and non-invasive diagnostic tool in many gastroenterological conditions. The rationale of hydrogen-breath tests is based on the concept that part of the gas produced by colonic bacterial fermentation diffuses into the blood and is excreted by breath, where it can be quantified easily. There are many differences in the methodology, and the tests are increasingly popular. AIM: The Rome Consensus Conference was convened to offer recommendations for clinical practice about the indications and methods of H2-breath testing in gastrointestinal diseases. METHODS: Experts were selected on the basis of a proven knowledge/expertise in H2-breath testing and divided into Working Groups (methodology; sugar malabsorption; small intestine bacterial overgrowth; oro-coecal transit time and other gas-related syndromes). They performed a systematic review of the literature, and then formulated statements on the basis of the scientific evidence, which were debated and voted by a multidisciplinary Jury. Recommendations were then modified on the basis of the decisions of the Jury by the members of the Expert Group. RESULTS AND CONCLUSIONS: The final statements, graded according to the level of evidence and strength of recommendation, are presented in this document; they identify the indications for the use of H2-breath testing in the clinical practice and methods to be used for performing the tests.