Use of tofacitinib as first or second-line therapy is associated with better outcomes in patients with ulcerative colitis: data from a real-world study.

BACKGROUND: Data 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 METHODS: A 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. RESULTS: We 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. CONCLUSIONS: Our 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.

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.

Replacement of Adalimumab Originator to Adalimumab Biosimilar for a Non-Medical Reason in Patients with Inflammatory Bowel Disease: A Real-life Comparison of Adalimumab Biosimilars Currently Available in Italy.

BACKGROUND AND AIMS: Adalimumab (ADA) biosimilars have been included into the therapeutic armamentarium of inflammatory bowel disease (IBD); however, comparative data on the efficacy and safety of the different ADA biosimilars after replacing the ADA originator for a non-medical reason remains scarce. We aimed to compare in a real-life setting the efficacy and safety of four ADA biosimilars SB5, APB501, GP2017, and MSB11022 in IBD patients after replacing the originator for a non-medical reason. METHODS: A multicenter retrospective study was performed on consecutive IBD patients, analyzing clinical, laboratory, and endoscopic data. The primary endpoints of the study were maintenance of clinical remission and safety of the different biosimilars. RESULTS: 153 patients were enrolled, 26 with UC and 127 with CD. Clinical remission was maintained in 124 out of 153 (81%) patients after a median (IQR) follow-up of 12 (6-24) months, without any significant difference between the four ADA biosimilars. ADA biosimilars dosage was optimized in five patients (3.3%). Loss of remission was significantly higher in UC patients (10/26 patients, 38.5%) than in CD patients (19/127 patients, 14.9%, p<0.025). Adverse events occurred in 12 (7.9%) patients; the large majority were mild. CONCLUSIONS: No difference in efficacy and safety was found between ADA biosimilars when used to replace the ADA originator for a non-medical reason. However, in UC patients the replacement of ADA originator for this reason should be carefully assessed.

Adalimumab Biosimilar GP2017 versus Adalimumab Originator in Treating Patients with Inflammatory Bowel Diseases: A Real-Life, Multicenter, Observational Study.

The approval of adalimumab (ADA) biosimilars for inflammatory bowel disease (IBD) has reduced the cost of treatment. While several ADA biosimilars are currently available, comparative data on the ADA biosimilar GP2017 (HyrimozTM) and its originator (HumiraTM) in IBD are lacking. We compared the efficacy and safety of GP2017 versus originator in IBD outpatients in an Italian real-life setting. This retrospective analysis enrolled consecutive IBD patients with complete clinical, laboratory, and endoscopic data. Clinical activity was assessed with the Mayo score in ulcerative colitis (UC) and the Harvey-Bradshaw Index in Crohn's disease (CD). The primary endpoints were the induction of remission and the safety of GP2017 versus ADA originator. One hundred and thirty-four patients (30.6% with UC and 69.4% with CD, median age 38 years) were enrolled: 62 (46.3%) patients were treated with GP2017, and 72 (53.7%) with ADA originator; 118 (88.1%) patients were naïve to ADA. Clinical remission was obtained in 105 (78.4%) patients, during a median follow-up of 12 months, 82.3% and 75% in the GP2017 and ADA originator groups, respectively (p = 0.311). Treatment was well tolerated in both groups. This analysis of real-world data suggests that GP2017 and its originator are equivalent in terms of efficacy and safety in patients with IBD.

Water-immersion technique during standard upper endoscopy may be useful to drive the biopsy sampling of duodenal mucosa in children with celiac disease.

OBJECTIVE: To evaluate the accuracy of the water-immersion technique during upper endoscopy in recognizing the duodenal villous pattern in a series of children who were undergoing endoscopy to obtain duodenal biopsy for histological analysis. MATERIALS AND METHODS: The water-immersion technique was performed in 19 children. Endoscopic findings were compared with histology. Results were assessed on per biopsy analysis and per patient analysis, taking into account the worst endoscopic finding in each patient and correlating it with the worst histological diagnosis. RESULTS: Per biopsy analysis: A total of 57 biopsy specimens were obtained and assessed. The endoscopic duodenal investigation correctly identified 53 areas (93%), which corresponded to histology, giving it an accuracy rate of 93%. Per patient analysis: The worst histology of the duodenal bulb was predicted by endoscopy in 18 of the 19 enrolled patients (95%), whereas the worst histopathological lesion of the second portion of the duodenum was recognized in 100% of cases. On the whole, therefore, the endoscopist suggested a diagnosis of celiac disease in 11 patients, with both positive and negative predictive values of 100%. CONCLUSIONS: The water-immersion technique during upper endoscopy is highly accurate in recognizing the duodenal villous pattern in subjects who need a duodenal investigation. Our findings encourage a cost-saving and patient-retaining approach to the diagnosis of celiac disease by driving biopsy and reducing the number of duodenal samplings.

The water immersion technique is easy to learn for routine use during EGD for duodenal villous evaluation: a single-center 2-year experience.

GOALS: We investigated the learning parameters of the immersion technique for the assessment of marked villous atrophy (MVA), during routine esophagogastroduodenoscopy (EGD). BACKGROUND: The immersion technique offers a proven possibility of enhancing the sensitivity of endoscopy in detecting duodenal villous atrophy patterns. STUDY: Nine endoscopists with at least 2 years of experience, who had previously been trained to perform the immersion technique, searched for duodenal villi during routine EGD. In a 2-year study, duodenal villi were evaluated underwater duodenoscopy in 432 patients from whom duodenal biopsies had been, for various reasons, obtained. The endoscopic findings were compared with the histology. The learning parameters of the water immersion technique and the accuracy in detecting subjects with MVA were observed. RESULTS: A total of 28 (6.5%) patients with MVA were identified during endoscopy by the trained endoscopists. All these patients were diagnosed as being celiac patients. The sensitivity, specificity, and accuracy (positive and negative predictive values) of the immersion technique in detecting MVA patterns, irrespective of the endoscopist who performed the examination, were always 100%. CONCLUSIONS: The underwater evaluation of the duodenum can be efficiently and regularly performed during routine EGD by endoscopists with 2 years of experience, after a specific, brief training period. This procedure is simple, feasible, and can accurately detect MVA patterns.

Bacillus subtilis isolated from the human gastrointestinal tract.

As part of an ongoing study to determine the true habitat of Bacillus species, we report here the isolation and characterisation of Bacillus subtilis from the human gastrointestinal tract (GIT). Strains were obtained from ileum biopsies as well as from faecal samples and their biotypes defined. 16S rRNA analysis revealed that most isolates of B. subtilis were highly conserved, in contrast to RAPD-PCR fingerprinting that showed greater diversity with 23 distinct RAPD types. The majority of B. subtilis strains examined possessed features that could be advantageous to survival within the GIT. This included the ability to form biofilms, to sporulate anaerobically and secretion of antimicrobials. At least one isolate was shown to form spores that carried an exosporium, a loosely attached outer layer to the mature endospore, this being the first report of B. subtilis spores carrying an exosporium. This study reinforces a growing view that B. subtilis and probably other species have adapted to life within the GIT and should be considered gut commensals rather than solely soil microorganisms.

Optimal band imaging system: a new tool for enhancing the duodenal villous pattern in celiac disease.

BACKGROUND: The optimal band imaging (OBI) system is a new technology that can select better spectral images decomposed from ordinary endoscopic images. This technology, first introduced as "FUJI Intelligent Color Enhancement," enhances the contrast of the mucosal surface without the use of dyes. OBJECTIVE: This study aimed to evaluate the potential of OBI for predicting the duodenal villous morphologic characteristics in patients with suspected celiac disease. DESIGN: This study was designed as an open, prospective, single-center trial. Duodenoscopy was performed with a high-resolution magnification view, in association with OBI spectral processing. Duodenal villous patterns were evaluated and classified as normal, partially atrophic, or markedly atrophic. The endoscopic results were then compared with the histologic diagnosis. SETTING: Endoscopy unit at the A. Gemelli University Hospital of Rome, Italy. PATIENTS: Sixty-one patients undergoing upper endoscopy for clinical history of malabsorption or serologic suspicion for celiac disease were included in the study. RESULTS: From OBI sets using red, green, and blue wavelength combinations that ranged from 400 to 580 nm, the endoscopist was able to find marked villous atrophy of the duodenum in 16 subjects, partial villous atrophy in 9 subjects, and normal villi in the remaining 36 subjects. The sensitivity, specificity, and positive and negative predictive values of the OBI-based duodenoscopy were 100% accurate in the evaluation of villous patterns. CONCLUSIONS: High-resolution magnification endoscopy with OBI allows clear visualization of the duodenal villous pattern. The OBI system may play a potential role in optimizing the diagnostic accuracy of endoscopy in celiac disease.

Role of probiotics in patients with Helicobacter pylori infection.

Probiotics are defined as live, nonpathogenic microbial feeds or food supplements that exert a positive influence on their host by altering his microbial balance. As shown in several studies, probiotics also possess a direct antimicrobial effect; for this reason, several authors have tested a possible application in patients with Helicobacter pylori infection. In particular, probiotics may compete directly with H. pylori, possibly through the inhibition of adherence, as well as produce metabolites and antimicrobial molecules, properties supported only by animal or in vitro data. Moreover, implementation of standard anti-H. pylori regimens with probiotics can also improve patients' compliance to therapy, reducing the occurrence of antibiotic-related adverse events. The same effect was also reported after using a combination of two different prebiotics such as butyric acid and inulin in patients who underwent H. pylori eradication treatment. Based on current data, even though an effect against H. pylori has been described, probiotics cannot be considered as an alternative to standard anti-H. pylori treatment. Nevertheless, their use in association with standard anti-H. pylori treatment may be advisable, as they are able to improve patient compliance by reducing antibiotic-related adverse events, thus increasing the number of patients completing the eradication therapy.

Role of the "immersion technique" in diagnosing celiac disease with villous atrophy limited to the duodenal bulb.

GOALS: To investigate if the so-called immersion technique during upper endoscopy may be helpful to predict patterns of villous atrophy restricted to the duodenal bulb. BACKGROUND: Patients with celiac disease may have a patchy distribution of duodenal villous atrophy. In some cases, mucosa of duodenal bulb may be the only intestinal area involved. The immersion technique is a novel procedure that allows visualizing duodenal villi directly during endoscopy. STUDY: With this prospective study, the immersion duodenoscopy was performed in 67 celiac subjects to investigate their duodenal villous pattern. Villi were evaluated both in the first and in the second duodenal segment and judged as present or absent (flat mucosa). Results were compared with histology as reference. RESULTS: Among celiac subjects, 49 were newly diagnosed and 18 previously diagnosed celiac patients. Four (8%) newly diagnosed and 7 (39%) previously diagnosed celiac subjects had an extension of the villous atrophy (flat mucosa) limited to the duodenal bulb. The sensitivity, specificity, and positive and negative predictive values of the immersion-based duodenal investigation in predicting areas of duodenal villous atrophy was always 100%. CONCLUSIONS: Immersion technique may be useful for directing duodenal biopsies in celiac subjects with a patchy distribution of villous atrophy. This procedure can avoid blinded sampling of the duodenal mucosa and enhance the diagnostic yield.

Malabsorption in psoriatic patients: cause or consequence?

OBJECTIVE: The etiopathogenesis of psoriasis is still unclear. Associations between gut and skin diseases are well known, since psoriatic patients show a high prevalence of coeliac disease. Small-bowel abnormalities can cause clinical or, more frequently, laboratory alterations that give rise to malabsorption. The aim of the study was to evaluate the prevalence of malabsorption in psoriatic patients. MATERIAL AND METHODS: Fifty-five (29 M, 26 F, mean age 51+/-8 years) psoriatic patients in the Dermatology Centre of our hospital and 65 healthy controls (36 M, 29 F, mean age 47+/-9 years) were screened for malabsorption using a D-xylose test. Psoriatic subjects who resulted positive were further investigated in order to reach a better characterization of the malabsorption using serum antigliadin, anti-endomysium and anti-transglutaminase antibodies, H2 lactulose breath test, the parasitological faecal test and colonoscopy with retrograde ileoscopy. RESULTS: Altered D-xylose absorption was found in 60% (33/55) of psoriatic patients and in 3% (2/65) of controls. Of the former, 6% had coeliac disease, 21% had bacterial overgrowth, 3% had parasitic infections and 1 patient presented eosinophilic gastroenteritis. CONCLUSIONS: Malabsorption was more prevalent among psoriatic patients than among controls. Coeliac disease, bacterial overgrowth, parasitic infestations and eosinophilic gastroenteritis could be possible causes of malabsorption in these patients. Further studies are needed to clarify the pathogenesis and possible causative associations between gut and skin diseases.

Rifaximin-based regimens for eradication of Helicobacter pylori: a pilot study.

BACKGROUND: Triple therapy is the treatment of choice for Helicobacter pylori-infected patients with an eradication rate ranging from 70 to 85%. Poor compliance and antibiotic resistance are the main causes of treatment failure. The aim of the present study was to assess the efficacy of rifaximin, a poorly absorbed antibiotic, for H. pylori eradication. METHODS: We enrolled 48 consecutive H. pylori-positive patients affected. They were randomized to receive two 7-day rifaximin-based triple therapies: rifaximin tablets 400 mg t.i.d., esomeprazole 40 mg o.d. and clarithromycin 500 mg b.i.d. (CRE) or levofloxacin 500 mg o.d. (LRE). H. pylori eradication was assessed using a (13)C-urea breath test 4 weeks after the end of therapy. Treatment compliance and the incidence of side effects were also evaluated. RESULTS: No dropouts were observed. The eradication rate both on intention-to-treat and per-protocol analysis did not show significant differences between groups: 58% (14/24 patients) in group 1 and 42% (10/24 patients) in group 2 (p = 0.24, OR 1.96, 95% CI 0.62-6.18). No significant differences in patients' compliance and incidence of side effects were found between groups. CONCLUSIONS: Rifaximin-based therapy showed optimal compliance but a limited eradication rate compared to standard first-line treatment. Further investigations are needed to evaluate different dosages and combinations.

Interaction between Helicobacter pylori infection and untreated coeliac disease on gastric histological pattern.

OBJECTIVE: Helicobacter pylori infection is the major agent of gastric damage. Coeliac disease may affect the morphology and function of the entire gastrointestinal tract from the stomach to the colon. The aim of this study was to assess the gastric histological pattern in patients with H. pylori and untreated coeliac disease. MATERIAL AND METHODS: We retrospectively enrolled 183 H. pylori-positive patients with (85, group A) and without (98, group B) untreated coeliac disease. The groups were similar for age, gender and smoking habit, and all the patients came from the same geographical area. Histological evaluation of gastric pattern was performed on 4 biopsies (2 in the antrum, 2 in the corpus). Gastric damage was classified according to the modified Sydney System. Diagnosis of H. pylori infection was based on positivity to histology. The chi-square test was used to assess differences between groups. A p-value <0.05 was considered significant. RESULTS: Group A showed a significantly higher prevalence of follicular gastritis than group B (23.5% versus 12.2%, p=0.045). A significantly lower prevalence of atrophic gastritis was observed in group A compared with that in group B (6% versus 22.5%, p=0.002). The prevalence of chronic superficial gastritis, activity degree and intestinal metaplasia was similar between the two groups. CONCLUSIONS: In patients with H. pylori infection, untreated coeliac disease could represent a risk factor for follicular gastritis and is associated with a lower prevalence of atrophic gastritis. The complex interaction between H. pylori and untreated coeliac disease on Th-1/Th-2 balance in the gastric mucosa could explain these results.