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Background: Ustekinumab (UST) and vedolizumab (VDZ) are biologic therapies for moderate-to-severe Crohn's disease (CD) in patients who failed or had contraindication to anti-TNF treatment., Aims: To evaluate ustekinumab efficacy as third-line treatment after swapping from VDZ for failure., Methods: We conducted a monocentric, retrospective, observational study where CD patients were followed for 12 months from the beginning of UST therapy. We assessed clinical activity (HBI) and laboratory markers (CRP) at the initiation of UST therapy (T0) and after 2(T2), 6(T6) and 12(T12) months. Endoscopic activity was recorded at T0 and T12. We registered data regarding their clinical history and previous biologic treatments. Steroid-free clinical remission was defined as HBI ≤ 4 without need for steroids. Clinical response was defined as HBI reduction of at least three points or the suspension of steroids., Results: 27 CD patients treated with UST after VDZ failure had a minimum follow up of 12 months and were included. All patients had previously been treated with anti-TNF agents. After 12 months, steroid-free clinical remission was evident in 15 (55.5%) patients, 5 (18.5%) had clinical response, while 7 (26%) had suspended for failure or persisted on treatment after optimization., Conclusions: Ustekinumab should be considered as third-line biologic treatment in multi-refractory CD patients., Competing Interests: Conflict of interest PG received honoraria from Janssen, Abbvie, Pfizer, Celgene, Takeda, Ferring, MSD, Amgen, Alfa-Sigma and he participated in a company sponsored speaker's bureau of Abbvie, Janssen, Takeda, FGerring, MSD, Sofar, Chiesi. FR reveived honoraria from Janssen, Abbvie, Pfizer, Takeda, Ferring, MSD and he participated in a company sponsored speaker's bureau of Abbvie, Jansen, Takeda, Ferring, MSD, Sofar, Chiesi. The other authors have no competing interest to declare., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Italy has been one of the most affected countries in the world by COVID-19. There has been increasing concern regarding the impact of COVID-19 on patients with inflammatory bowel disease (IBD), particularly in patients treated with immunosuppressants or biologics. The aim of our study is to understand the incidence of COVID-19 in a large cohort of patients with IBD. Furthermore, we analyzed possible risk factors for infection and severity of COVID-19., Methods: This was an observational study evaluating the impact of COVID-19 on IBD patients in a single tertiary center. A 23 multiple-choice-question anonymous survey was administered to 1200 patients with IBD between March 10th and June 10th 2020., Results: 1158 questionnaires were analyzed. The majority of patients had Crohn's disease (CD) (60%) and most of them were in clinical remission. Among the 26 patients (2.2%) who tested positive for COVID-19, only 5 (3CD) were on biological treatment and none required hospitalization. Two patients died and were on treatment with mesalazine only. Of the 1158 patients, 521 were on biological therapy, which was discontinued in 85 (16.3%) and delayed in 195 patients (37.4%). A worsening of IBD symptoms was observed in 200 patients on biological therapy (38.4%). Most of these patients, 189 (94.5%), had stopped or delayed biological treatment, while 11 (5.5%) had continued their therapy regularly (p<0.001)., Conclusions: Our data are in line with the current literature and confirm a higher incidence compared to the general population. Biological therapy for IBD seems to not be a risk factor for infection and should not be discontinued in order to avoid IBD relapse., Competing Interests: Conflict of Interest None declared., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Simkania negevensis is an obligate intracellular Gram-negative bacterium (family Simkaniaceae, order Chlamydiales) that has been isolated from domestic and mains water supplies, is able to infect human macrophages, and can induce an inflammatory response in the host., Methods: From June to December 2016, in a single-center observational study, colonic Crohn's disease patients and controls (subjects undergoing screening for colorectal cancer) underwent blood tests to identify serum-specific immunoglobulin G (IgG) and immunoglobulin A (IgA) to S. negevensis and a colonoscopy with biopsies for detection of S. negevensis DNA by polymerase chain reaction (PCR)., Results: Forty-three Crohn's disease patients and 18 controls were enrolled. Crohn's disease patients had higher prevalence of IgA antibodies to S. negevensis compared with controls (20.9% versus 0%, p = 0.04). Simkaniaceae negevensis DNA was detected in 34.9% and 5.6% of intestinal biopsies in Crohn's disease patients and controls, respectively (p = 0.02). All Crohn's disease patients with PCR-positive biopsies for S. negevensis were IgG seropositive, with specific IgA in 60% of them (p < 0.001). Immunosuppressive therapies, extraintestinal manifestations, or disease activity did not influence the presence of S. negevensis in the Crohn's disease population., Conclusions: We identified S. negevensis in Crohn's disease patients by demonstrating the presence of S. negevensis mucosal DNA and seropositivity to the bacterium. These results could support the presence of an acute or persistent S. negevensis infection and suggest a possible role in the pathogenesis of Crohn's disease.

Background: "Real-life" data of retention rate and persistence of adalimumab in inflammatory bowel disease are still limited., Aims: To analyze retention rate, persistence, and safety of adalimumab in a 9-year real-life cohort of inflammatory bowel disease patients., Methods: In this observational, retrospective single-center study, all adult patients treated with adalimumab as the first- and second-line biological treatment for steroid-dependent or refractory inflammatory bowel disease between March 2008 and March 2017 were included. Primary outcomes were persistence, retention rate, and adverse events; the secondary outcome was the identification of predictors of withdrawal., Results: Ninety-six out of 181 patients (53%) withdrew their first course of adalimumab. The retention rate was 47% and 46.9% in Crohn's disease and ulcerative colitis patients, respectively; median persistence was 26 and 24 months in CD and UC patients, respectively. The cumulative probability of treatment persistence was 80.2%, 54.5%, and 29.6% and 69.6%, 40.4%, and 21.5% in CD and UC patients, respectively. The incidence rate of any adverse event was 12.5/100 patients-year; severe adverse events were 1.7/100 patients-year. The Cox regression revealed that CD patients with baseline disease duration > 72 months have a higher likelihood for withdrawal due to failure and/or adverse events (HR 1.62, 95% CI 1-2.62, p = 0.04); no predictors of discontinuation were found in UC., Conclusions: Adalimumab showed a great persistence in the first 12 months of therapy and excellent safety profile. Early treatment of CD patients could increase efficacy and reduce the adverse event rate.

Inflammatory bowel diseases have a natural course characterized by alternating periods of remission and relapse. Disease flares occur in a random way and are currently unpredictable for the most part. Predictors of benign or unfavourable clinical course are required to facilitate treatment decisions and to avoid overtreatment. The present article provides a literature review of the current evidence on the main clinical, genetic, endoscopic, histologic, serologic and fecal markers to predict aggressiveness of inflammatory bowel disease and discuss their prognostic role, both in Crohn's disease and ulcerative colitis. No single marker seems to be reliable alone as a flare predictor, even in light of promising evidence regarding the role of fecal markers, in particular fecal calprotectin, which has reported good results recently. In order to improve our daily clinical practice, validated prognostic scores should be elaborated, integrating clinical and biological markers of prognosis. Finally, we propose an algorithm considering clinical history and biological markers to intercept patients with high risk of clinical relapse.

Supplementation with n-3 polyunsaturated fatty acids (n-3 PUFAs) may be beneficial for patients with inflammatory bowel diseases (IBD). In this study we analyzed the pharmacokinetic profile of eicosapentaenoic acid (EPA), as the free fatty acid (FFA), in an enteric-coated preparation, in 10 ulcerative colitis (UC) and 10 Crohn's disease (CD) patients and 15 healthy volunteers (HV). Subjects received 2 g daily of EPA-FFA for 8 weeks. Plasma phospholipid and red blood cell (RBC) membrane fatty acid content were measured by gas chromatography-mass spectrometry. There was a rapid incorporation of EPA into plasma phospholipids by 2 weeks and a slower, but highly consistent, incorporation into RBC membranes (4% total fatty acid content; coefficient of variation 10-16%). There was a concomitant reduction in relative n-6 PUFA content. Elongation and desaturation of EPA into docosahexaenoic acid (DHA) via docosapentaenoic acid (DPA) were apparent and DHA content also increased in membranes. EPA-FFA is well tolerated and no difference in the pharmacokinetic profile of n-3 PUFA incorporation was detected between IBD patients and HV. Our data support the concept that EPA can be considered the "universal donor" with respect to key n-3 PUFAs and that this enteric-coated formulation allows long term treatment with a high level of compliance.

The origin of inflammatory bowel disease is unknown. Attempts have been made to isolate a microorganism that could explain the onset of inflammation, but no pathological agent has ever been identified. Johne's disease is a granulomatous chronic enteritis of cattle and sheep caused by Mycobacterium avium subspecies paratuberculosis (MAP) and shows some analogies with Crohn's disease (CD). Several studies have tried to clarify if MAP has a role in the etiology of CD. The present article provides an overview of the evidence in favor and against the "MAP-hypothesis", analyzing the methods commonly adopted to detect MAP and the role of antimycobacterial therapy in patients with inflammatory bowel disease. Studies were identified through the electronic database, MEDLINE, and were selected based on their relevance to the objective of the review. The presence of MAP was investigated using multiple diagnostic methods for MAP detection and in different tissue samples from patients affected by CD or ulcerative colitis and in healthy controls. On the basis of their studies, several authors support a close relationship between MAP and CD. Although increasing evidence of MAP detection in CD patients is unquestionable, a clear etiological link still needs to be proven.