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.

Full-spectrum versus standard colonoscopy for improving polyp detection rate: A systematic review and meta-analysis.

BACKGROUND AND AIM: Full-spectrum endoscopy represents a new endoscopic platform allowing a panoramic 330 degree view of the colon, but evidence of its superiority over standard colonoscopy is still lacking. Our study is the first meta-analysis comparing the efficacy of full-spectrum endoscopy with standard colonoscopy. METHODS: Through a systematic literature review until May 2017, we identified eight randomized-controlled trials. Primary outcomes were polyp detection rate and adenoma detection rate, while cecal intubation time and total colonoscopy time were secondary outcomes. Direct meta-analysis was performed using a random effects model. RESULTS: No difference in terms of polyp detection rate and adenoma detection rate was found (risk ratio: 1.00, 95% confidence interval 0.89-1.12, P = 0.96, and 1.05, 0.94-1.17, P = 0.40, respectively). Adenoma miss rate resulted significantly in favor of full-spectrum endoscopy (risk ratio: 0.35, 0.25-0.48, P < 0.01), although the difference was not significant for greater (>5 mm) and pedunculated lesions (risk ratio: 0.38, 0.09-1.60, P = 0.19, and risk ratio: 0.15, 0.01-3.00, P = 0.21, respectively). Cecal intubation time was not different between the two techniques (mean standardized difference: 0.22 min, -1.18 to 1.62, P = 0.76), while total colonoscopy time was significantly shorter when adopting full-spectrum endoscopy (mean difference: -2.60, -4.60 to -0.61, P = 0.01). Sensitivity analysis confirmed all the findings. CONCLUSIONS: Full-spectrum endoscopy appears as a promising and reliable technology able to significantly decrease the number of adenomas missed and procedural times, while its superiority over standard colonoscopy in terms of adenoma detection rate results is still unclear.

From chronic liver disorders to hepatocellular carcinoma: Molecular and genetic pathways.

Hepatocarcinogenesis is a process attributed to progressive genomic changes that alter the hepatocellular phenotype producing cellular intermediates that evolve into hepatocellular carcinoma (HCC). During the preneoplastic phase, the liver is often the site of chronic hepatitis and/or cirrhosis, and these conditions induce liver regeneration with accelerated hepatocyte cycling in an organ that is otherwise proliferatively at rest. Hepatocyte regeneration is accelerated by upregulation of mitogenic pathways involving molecular and genetic mechanisms. Hepatic growth factors, inhibitors and triggers may also play a role. This process leads to the production of monoclonal populations of aberrant and dysplastic hepatocytes that have telomerase re-expression, microsatellite instability, and occasionally structural aberrations in genes and chromosomes. Development of dysplastic hepatocytes in foci and nodules and the emergence of HCC are associated with the accumulation of irreversible structural alterations in genes and chromosomes even if the genomic basis of the malignant phenotype is largely heterogeneous. Therefore, a malignant hepatocyte phenotype may be produced by changes in genes acting through different regulatory pathways, thus producing several molecular variants of HCC. On these bases, a key point for future research will be to determine whether the deletions are specific, due to particular loci in the minimally deleted regions of affected chromosome arms, or whether they are non-specific with loss of large portions of chromosomes or entire chromosome arms leading to passive deletion of loci. The final aim is the possibility of identifying a step where carcinogenetic processes could be terminated.

Onset of liver damage after a single administration of infliximab in a patient with refractory ulcerative colitis.

We report the case of a patient with refractory ulcerative colitis who developed cholestatic acute liver damage after a single infusion of infliximab. Unusual aspects of this case were the early onset (after the first administration) of liver damage and the absence of antinuclear antibodies, alcohol intake, hepatotoxic drugs and all known viral and metabolic causes of hepatic injury. Moreover, no serological or morphological findings of primary sclerosing cholangitis were observed. The patient's liver damage resolved spontaneously within 6 weeks. Although a direct relationship between administration of infliximab and onset of acute liver damage could not be definitely established, our case suggests that infliximab may induce direct liver damage, the course of which is similar to acute cholestatic hepatitis and resolves following withdrawal of the drug.

Claritromycin resistance and Helicobacter pylori genotypes in Italy.

The relationship between H. pylori clarithromycin resistance and genetic pattern distribution has been differently explained from different geographic areas. Therefore, we aimed to assess the clarithromycin resistance rate, to evaluate the bacterial genetic pattern, and to search for a possible association between clarithromycin resistance and cagA or vacA genes. This prospective study enrolled 62 consecutive H. pylori infected patients. The infection was established by histology and rapid urease test. Clarithromycin resistance, cagA and vacA status, including s/m subtypes, were assessed on paraffin-embedded antral biopsy specimens by TaqMan real time polymerase chain reaction (PCR). Primary clarithromycin resistance was detected in 24.1 % of cases. The prevalence of cagA was 69.3 %, and a single vacA mosaicism was observed in 95.1 % cases. In detail, the s1m1 was observed in 23 (38.9 %) patients, the s1m2 in 22 (37.2 %), and the s2m2 in 14 (23.7 %), whereas the s2m1 combination was never found. The prevalence of cagA and the vacA alleles distribution did not significantly differ between susceptible and resistant strains. Primary clarithromycin resistance is high in our area. The s1m1 and s1m2 are the most frequent vacA mosaicisms. There is no a relationship between clarithromycin resistance and bacterial genotypic pattern and/or cagA positivity.

Small intestinal contrast ultrasonography-based scoring system: a promising approach for the diagnosis and follow-up of celiac disease.

BACKGROUND: Small intestinal ultrasonography with anechoic contrast agents (SICUS) has been shown to have a diagnostic accuracy on small bowel morphology similar to X-ray barium follow-through. Although extremely investigated by transabdominal ultrasonography, celiac disease, a common disorder of the small bowel, has been never studied by SICUS. AIM: To asses SICUS characteristics of celiac disease patients. PATIENTS AND METHODS: SICUS was performed using PEG 4000 as contrast agent. Twenty-three patients with celiac disease at the first diagnosis were enrolled and 30 healthy volunteers, matched for sex and age, were selected as control group. Celiac disease diagnosis was based on anti-gluten, anti-endomysium, and anti-transglutaminase positivity as well as jejunal histology. The following seven echographic parameters were considered: liquid endoluminal content before contrast, loop diameter, Kerckring's folds, peristaltic waves, ileal jejunalization, mesenteric lymphoadenomegaly, and Doppler resistance index (RI) of mesenteric superior artery. Statistical analysis was performed by Student's t test for unpaired data; one-way analysis of variance was used to correlate echographic and histologic pictures. RESULTS: Loop diameter, Kerckring's fold number, peristaltic waves, and Doppler RI appeared to be significantly different between celiac disease patients and controls. Additionally, liquid content, ileal jejunalization, and mesenteric lymphoadenomegaly were present only in the celiacs (52.1%, 47.7%, and 95.6%, respectively), but not in controls. Only Doppler RI values significantly correlated with the histologic degree of damage. CONCLUSIONS: SICUS could be a reliable and noninvasive technique to confirm a diagnosis of celiac disease performed using conventional investigations. The possibility of investigating the whole small bowel and the safety of repeating examinations could be useful in the follow-up of celiac patients.