Search

ABSTRACTBackgroundUstekinumab (UST) is an interleukin-12/interleukin-23 receptor antagonist recently approved for treating ulcerative colitis (UC) but with limited real-world data. Therefore, we evaluated the effectiveness and safety of UST in patients with UC in a real-world setting.Research design and methodsThis is a multicenter, retrospective, observational cohort study. The primary endpoints were the clinical remission rate (partial Mayo score, PMS, ≤1) and the safety of UST. Other endpoints were corticosteroid-free remission (CSFR) rate, clinical response rate (PMS reduction of at least 2 points), and fecal calprotectin (FC) reduction at week 24.ResultsWe included 256 consecutive patients with UC (M/F 139/117, median age 52). The clinical remission and clinical response rates at eight weeks were 18.7% (44/235) and 53.2% (125/235), respectively, and 27.6% (42/152) and 61.8% (94/152) at 24 weeks, respectively. At 24 weeks, CSFR was 20.3% (31/152), and FC significantly dropped at week 12 (p = 0.0004) and 24 (p = 0.038). At eight weeks, patients naïve or with one previous biologic treatment showed higher remission (p = 0.002) and clinical >response rates (p = 0.018) than patients previously treated with ≥ 2. Adverse events occurred in six patients (2.3%), whereas four patients (1.6%) underwent colectomy.ConclusionThis real-world study shows that UST effectively and safely treats patients with UC.

Background/Aim:Prevalence of gastroduodenal endoscopic and histological lesions may modify over time due to different factors. We assessed both macroscopic and histological lesions currently detected at upper endoscopy performed in routine practice. Patients and Methods:Clinical, endoscopic, and histological data of consecutive adult patients referred for upper endoscopy in the 28 participating centres were analysed. Only patients who underwent the first endoscopic examination were considered. Prevalence of erosive/ulcerative lesions, cancers and extensive precancerous lesions in the stomach, and Helicobacter pyloriinfection was computed. Results:A total of 1,431 patients underwent endoscopy for gastro-oesophageal reflux symptoms (31.5%), dyspepsia (29.4%), or alarm symptoms (18.5%). Erosive oesophagitis or Barrett’s oesophagus was detected in 210 (14.7%) cases, peptic ulcer in 49 (3.4%), and a neoplastic lesion in 17 (1.2%). H. pyloriwas present in 201 (22.6%) cases, and extensive precancerous lesions on gastric mucosa in 46 (5.6%) patients. Gastric lesions were more prevalent in patients aged ≥50 years (26% vs. 18%; p= 0.001), and peptic ulcers were more frequently detected in patients with H. pylori(9.4% vs. 2.3%; p= 0.001) and in males (5.8% vs. 1.6%; p= 0.001), while neoplastic lesions in patients with alarm symptoms (3.8% vs. 0.6%; p= 0.001). Conclusions:The overall endoscopic lesions were more prevalent in patients aged ≥50 years, peptic ulcer and erosions were more frequent in H. pylori-infected patients, and extensive gastric precancerous lesions were present in less than 6% of cases.

ABSTRACTBackgroundData regarding the real-world (RW) use of tofacitinib (TOF) in patients with ulcerative colitis (UC) are limited. We aimed to investigate TOF’s RW efficacy and safety in Italian UC patients.Research design and methodsA retrospective assessment of clinical and endoscopic activity was performed according to the Mayo score. The primary endpoints were to evaluate the effectiveness and safety of TOF.ResultsWe enrolled 166 patients with a median follow-up of 24 (IQR 8–36) weeks. Clinical remission was achieved in 61/166 (36.7%) and 75/166 (45.2%) patients at 8-week and 24-week follow-ups, respectively. The optimization was requested in 27 (16.3%) patients. Clinical remission was achieved more frequently when TOF was used as a first/second line rather than a third/fourth line treatment (p = 0.007). Mucosal healing was reported in 46% of patients at the median follow-up time. Colectomy occurred in 8 (4.8%) patients. Adverse events occurred in 12 (5.4%) patients and severe in 3 (1.8%). One case of simple Herpes Zoster and one of renal vein thrombosis were recorded.ConclusionsOur RW data confirm that TOF is effective and safe in UC patients. It performs remarkably better when used as the first/second line of treatment.

ABSTRACTBackgroundVedolizumab (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.Results729 patients (475 with UC and 254 with CD), median follow-up of 18 (IQR 6-36) months, were enrolled. Clinical remission at the 6thmonth 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 6thmonth 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).ConclusionWe found differences when using VDZ in UC vs CD in real life. These parameters can help the physician predict this drug’s longterm efficacy.

ABSTRACTIntroductionChronic idiopathic constipation is a common gastrointestinal disorder whose treatment is still far from being satisfactory for patients. Osmotic laxatives, in particular polyethylene glycol, are the first-line approach, but new emerging pharmacological agents may be useful in refractory patients.Areas coveredPublished articles regarding the development and clinical efficacy of new agents in treating chronic idiopathic constipation were reviewed. Among emerging agents, elobixibat, a drug blocking the reabsorption of bile acids, is a promising one, especially in slow transit constipation. Linaclotide, lubiprostone and plecanatide, by a secretagogue action, improve stool consistency and increase colonic transit. Apart from prucalopride, approved in Europe for refractory chronic idiopathic constipation patients, the selective 5-HT4 agonists velusetrag and naronapride are in advanced development. In addition, relamorelin, a ghrelin agonist, seems promising for accelerating colonic transit.Expert opinionSeveral new promising drugs have been released with the potential to be effective in the treatment of chronic idiopathic constipation. On the other hand, the experience with these new agents is still limited, especially for long-term treatment. Another important point is that these new treatments for chronic idiopathic constipation are not available worldwide and their use could be somewhat limited by their still relatively high cost.

Background: Functional gastrointestinal disorders account for at least a third of visits togastroenterology clinics. Despite pathophysiological complexity, impaired gut motility may be frequentlypresent in these disorders. Introduction: Prokinetics are a class of drugs that promote gastrointestinal motility, accelerate transit,and potentially improve digestive symptoms. Several prokinetic agents with a great variety of mechanismsof action are available. Aim: The purpose of this paper is to update our current knowledge about the efficacy and safety of prokinetics.Methods: A literature search on efficacy and safety of prokinetics was carried out using the online databasesof Pubmed, Medline, and Cochrane. Results: Based on the action of different receptors, prokinetics mainly comprise dopamine antagonists,5HT4 agonists, motilin agonists, ghrelin agonists, and cholinergic agonists. Prokinetics have thepotential to improve motility function in all segments of the digestive tract, from the esophagus to thecolon. In particular, drug international agencies have approved antidopaminergic metoclopramide forthe treatment of gastroparesis and serotoninergic prucalopride for chronic constipation not responsiveto traditional laxatives. Arrhythmias by QT prolongation and galactorrhea by prolactin stimulation arethe more frequent side effects related to prokinetics use. Conclusion: Old and new prokinetics are effective in ameliorating digestive motility disorders and relatedsymptoms and are widely prescribed. Special attention should be paid to the potential adverseevents of these agents.

Background: Irritable bowel syndrome (IBS) is the most frequently diagnosed functional gastrointestinal disorder. It is characterised by abdominal pain, bloating and changes in bowel habits that can have a serious impact on the patient's quality of life. Treatment strategies are based on the nature and severity of the symptoms, the degree of functional impairment of the bowel habits, and the presence of psychosocial disorders. The purpose of this review is to update our current knowledge of therapeutic approach of this disorder. Method: A literature search for IBS therapy was carried out using the online databases of Pubmed, Medline and Cochrane. Results: An ideal treatment begins by explaining this condition and providing reassurance to the patients. There is limited evidence for the efficacy, and tolerability of the therapies currently available for the treatment of IBS. There is also a limited availability of pharmacological agents licensed specifically for the treatment of IBS subtypes, although new agents have been recently proposed to this goal. Furthermore, patients often associate their complaints with the ingestion of foods containing FODMAPs (fermentable oligo-di-monosaccharides, and polyols) and gluten derivates and a personalized diet can be proposed. However, more severe symptoms can be associated with greater levels of psychosocial problems and a psychological approach and antidepressant drugs can be needed. Conclusion: The treatment of IBS remains focused on treating the patient's predominant, or most troublesome, symptoms. New promising treatments have recently become available for the treatment of IBS but long term studies are still needed.

ABSTRACTIntroduction: Chronic constipation (CC) is a common gastrointestinal disorder with limited treatment options. Linaclotide is a potent peptide agonist of the guanylate cyclase-C receptor. This action activates intracellular conversion of guanosine 5-triphosphate to cyclic guanosine monophosphate resulting in the stimulation of intestinal fluid secretion. Linaclotide is a promising new agent for refractory constipation.Areas covered: All published articles regarding the development, clinical efficacy, and safety of linaclotide in treating CC were reviewed. Pharmacodynamics, pharmacokinetics, and metabolism of this secretagogue agent were examined. Clinical studies showed that linaclotide increases the number of spontaneous bowel movements and stool consistency scores. Overall, patients reported relief from abdominal discomfort and severity of constipation. Finally, linaclotide has a good safety profile, with diarrhea being the main side effect.Expert opinion: Linaclotide appears to be a well-tolerated and effective agent for patients with CC, and could be effectively combined with other drugs in patients with refractory constipation. However, data on the efficacy and safety of linaclotide in pediatric patients and in opioid-induced constipation are currently limited and more studies need to be undertaken.

ObjectiveIBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucrase–isomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase–isomaltase (SI) gene variants for their potential relevance in IBS.DesignWe sequenced SIexons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p.Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SIcoding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population.ResultsCSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case–control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroidesfaecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05).ConclusionsSIgene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.

Our study aims to determine the age of onset of adult-type hypolactasia in Sardinians, and to establish the age at which genotyping of the C/T-13910 variant can be used reliably in the diagnosis of lactose malabsorption.

Our study aims to determine the age of onset of adult-type hypolactasia in Sardinians, and to establish the age at which genotyping of the C/T-13910 variant can be used reliably in the diagnosis of lactose malabsorption. A lactose breath hydrogen test was given to 383 randomly selected patients, from 3 to 19 years old. The C/C-13910 genotype was found in 90% of patients; the frequency of the positive lactose breath hydrogen test increased with age and reached a prevalence of 85% at 9 years. In Sardinians, adult-type hypolactasia becomes phenotypically evident in all individuals older than 9 years, suggesting that this should be considered the minimum age at which the genetic test for lactase nonpersistence should be applied.