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Background: Risk factors for colectomy following an episode of acute severe ulcerative colitis (ASUC) have been well studied, but data examining the early complications following an episode is limited. Objectives: We aimed to evaluate the prevalence and risk factors for medical and surgical complications within 90 days of an ASUC admission and determine if a high-intensity induction infliximab dose is associated with these complications. Design: Retrospective analysis. Methods: We conducted a retrospective study of ASUC admissions between January 2015 and July 2021 at a tertiary hospital. The primary outcome was the prevalence of total, medical and surgical complications within 90 days following an ASUC admission. Multivariate linear regression analysis assessed for factors associated with the prevalence of complications. Results: A total of 150 patients had 186 hospital admissions for ASUC. In total, 101/186 (54.3%) admissions required rescue medical therapy. Standard infliximab induction occurred in 65/100 admissions, accelerated infliximab induction in 35/100 and cyclosporine in 1/100 of admissions. In total, 117 complications, including 74/117 (63.2%) medical and 43/117 (36.8%) surgical complications, arose. Low serum albumin was independently associated with a higher incidence of total [β = −0.08 (95% confidence interval (CI): −0.15, −0.01), p = 0.03] and surgical complications [β = −0.1 (95% CI: −0.18, −0.001), p = 0.047], while an increased age was associated with increased incidence of surgical complications [β = 0.06 (95% CI: 0.01, 0.12), p = 0.02]. A higher Charlson score was associated with increased medical complications [β = 0.12 (95% CI: 0.01, 0.24), p = 0.03]. Infliximab induction dose intensity was not associated with an increased incidence of any complications. Conclusion: Early complications following an ASUC admission is prevalent although the majority are not serious. Risk factors associated with complications include low serum albumin, older age and a higher comorbidity score. Induction infliximab dose intensity, however, is not a risk factor. [ABSTRACT FROM AUTHOR]

Background: Chromoendoscopy is preferred over high-definition white light endoscopy (HDWLE) for dysplasia surveillance in inflammatory bowel disease (IBD) patients, but is more time-consuming to perform and real-world evidence is limited. The prevalence of sessile serrated lesions (SSLs) in IBD patients is also unknown. Objective: To determine the yield of polypoid and non-polypoid dysplasia and SSLs in IBD patients undergoing dysplasia surveillance and the associations for these lesions. Design: A retrospective cohort study from a tertiary IBD centre. Methods: A keyword search of the colonoscopy reporting system was performed. IBD patients with colonic disease that underwent colonoscopy for surveillance between 1 February 2015 and 1 February 2018 were included. Clinical, endoscopic and histopathological outcomes were extracted for the analysis. Results: Of 2114 patients identified, 276 eligible colonoscopies in 126 patients were analysed. The median age at colonoscopy was 51 years (interquartile range: 42–58 years). 71/126 (56%) of colonoscopies were performed in male patients, with 57/126 (45%) having ulcerative colitis, 68/126 (54%) Crohn's colitis and 1/126 (0.79%) IBD-unspecified. The prevalence for any neoplasia was 75/276 (27%). The prevalence for all serrated lesions was 43/276 (16%). Increased age was a risk factor for finding a neoplastic lesion on both univariate and multivariate analyses. Chromoendoscopy was associated with twice the odds of finding a neoplastic lesion (odds ratio: 1.99, 95% confidence interval: 1.13–3.51, p = 0.02), on multivariate analysis. No factor was associated with an increased risk of finding a serrated lesion. Conclusion: Significant neoplastic lesions and serrated lesions were detected in 27% and 16% of colonoscopies performed in IBD patients, respectively, with the highest yield in older patients. Chromoendoscopy significantly increased neoplasia yield compared to HDWLE and still has a robust utility in this pragmatic real-world study. [ABSTRACT FROM AUTHOR]

Objective: To examine whether non‐medical switching of patients with inflammatory bowel disease (IBD) from originator infliximab to a biosimilar (CT‐P13, Inflectra) is safe and clinically non‐inferior to continued treatment with originator infliximab. Design: Prospective, open label, multicentre, parallel cohort, non‐inferiority study in seven Australian hospitals over 48 weeks, May 2017 – October 2019. Participants: Adults (18 years or older) with IBD receiving maintenance originator infliximab (Remicade) who had been in steroid‐free clinical remission for at least 12 weeks. Intervention: Managed program for switching patients in four hospitals from originator to biosimilar infliximab (CT‐P13); patients in three other hospitals continued to receive originator infliximab (control). Main outcome measures: Clinical disease worsening requiring infliximab dose escalation or change in therapy. Results: The switch group included 204 patients, the control group 141 patients with IBD. Ten patients in the control group (7%) and 16 patients switched to CT‐P13 (8%) experienced clinical deterioration; the adjusted risk difference (control v switch group) was –1.1 percentage points (95% CI, –6.1 to 8.2 percentage points), within our pre‐specified non‐inferiority margin of 15 percentage points. Serious adverse events leading to infliximab discontinuation were infrequent in both the switch (six, 3%) and control (six, 4%) groups. Conclusion: Switching patients with IBD from originator to biosimilar infliximab is safe and non‐inferior to continuing treatment with originator infliximab. Moreover, the introduction of biosimilar infliximab, by increasing market competition, has resulted in substantial cost savings for the Pharmaceutical Benefits Scheme. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Trystram et al paper. To view this article, visit https://doi.org/10.1111/apt.16312 [ABSTRACT FROM AUTHOR]

Firstly, we agree that uptake of biosimilar medications in Australia has been slower than expected owing to several factors, including those elucidated in the letter by Lim et al. Keywords: Pharmaceuticals; Medicolegal EN Pharmaceuticals Medicolegal 435 435 1 11/02/21 20211101 NES 211101 B I In reply: i b We thank Lim and colleagues1 for their insightful comments regarding the use biosimilar medicines in Australia; their letter highlights some pertinent issues. [Extracted from the article]

The article presents a case study of a 42-year-old male patient who was suffering from severe Crohn's colitis. It offers insights on the case with relevance to the Swiss cheese risk analysis and management model devised by researcher James Reason. Details on his drug administration, hospital discharge and death are presented. The contributing factors to his death are highlighted.

Background: An inverse relationship exists between inflammation and testosterone concentrations in non-inflammatory bowel disease (IBD) immune conditions but has not been objectively explored in the IBD male population. We aimed to characterize the distribution of testosterone concentrations in a cohort of males with IBD and identify any relationship between testosterone levels and disease activity., Methods: We conducted a prospective cross-sectional study of male IBD patients. Demographics, disease characteristics, sex-hormone concentration, gonadotropins, C-reactive protein, fecal calprotectin, and patient-reported outcomes on quality of life and erectile function were collected. Relationships between disease activity, biomarkers, patient-reported outcome scores, and testosterone levels were analyzed using univariate and multivariate linear regression analyses., Results: A total of 85 male IBD patients were included with a mean age 44 ± 14.1 years, of which 49.4% had Crohn's disease. Mean testosterone concentration was 15.4 ± 5.2 nmol/L and 17.6% had a serum testosterone <10.4 nmol/L. Active disease was associated with lower testosterone concentrations in univariate analysis (β ± SE = -0.25 ± -1.99, P = .02) but not in multivariate analysis (β -0.18 ± 1.75, P = .06). Testosterone concentrations were independently associated with sex hormone-binding globulin levels (β ± SE = 0.45 ± 0.04, P < .0001) and a younger age (β ± SE = -0.32 ± 0.04, P <.0001). Erectile function scores (5-item International Index of Erectile Function) were lower in IBD patients with a longer duration of disease (β ± SE = -0.24 ± 0.006, P = .04)., Conclusions: Lower testosterone concentrations in men with IBD may reflect confounding from other factors and are not independently associated with disease activity. Greater awareness and screening for sexual dysfunction should occur in males with IBD, particularly in those with a longer disease duration., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: A substantial proportion of patients with inflammatory bowel disease (IBD) on intravenous infliximab require dose intensification. Accessing additional intravenous infliximab is labour-intensive and expensive, depending on insurance and pharmaceutical reimbursement. Observational data suggest that subcutaneous infliximab may offer a convenient and safe alternative to maintain disease remission in patients requiring dose-intensified infliximab. A prospective, controlled trial is required to confirm that subcutaneous infliximab is as effective as dose-intensified intravenous infliximab, to identify predictors of disease flare and to establish the role of subcutaneous infliximab therapeutic drug monitoring., Methods and Analysis: The DISCUS-IBD trial is an investigator-initiated, prospective, multicentre, randomised, open-label non-inferiority study comparing the rate of disease flares in participants randomised to continue dose-intensified intravenous infliximab to those switched to subcutaneous infliximab after 48 weeks. Participants are adult patients with IBD in sustained corticosteroid-free remission on any regimen of dose-intensified infliximab up to a maximum of 10 mg/kg 4-weekly intravenously. Participants allocated to intravenous infliximab will continue infliximab at the same dose-intensified regimen they were receiving at study enrolment. Subcutaneous infliximab dosing will be stratified by prior intravenous infliximab dosing. Clinical (Harvey-Bradshaw Index, partial Mayo score), biochemical (C reactive protein, faecal calprotectin), pharmacokinetic (drug-level±antidrug antibodies) and qualitative data are collected 12-weekly until study conclusion at week 48. 13 sites across Australia will participate in recruitment to reach a calculated sample size of 120 participants., Ethics and Dissemination: Multisite ethics approval was obtained from the Health District Human Research Ethics Committee (HREC) at The Alfred Hospital under a National Mutual Acceptance (NMA) agreement (HREC/90559/Alfred-2022; Local Reference: Project 618/22, version 1.6, 2 March 2023). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. DISCUS-IBD was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR) prior to commencing recruitment., Trial Registration Number: ACTRN12622001458729., Competing Interests: Competing interests: RDL has received conference fees from Janssen and Celltrion Healthcare. AS has received speaker fees from Sandoz and received research support and advisory fees from AbbVie, Pfizer, and Arrow Pharmaceuticals. GJW has served as a speaker, a consultant or an advisory board member for Janssen, Galapagos, AbbVie, Ferring, Dr Falk Pharma, Nova Labs and Sandoz. GTM has received educational grants or research support from GESA, The Gutsy Group, NHMRC, MRFF, AbbVie, Janssen, Pfizer, Shire and Takeda; speaker fees from AbbVie, Ferring, Janssen, Orphan, Pfizer, Roche, Sandoz, Shire and Takeda and has serve on advisory boards for AbbVie, Emerge, Eli-Lilly, Gilead, Hospira, Janssen, Orphan, MSD, Pfizer, Shire and Takeda. KL declares speaker fees, advisory Board fees and/or conference travel/registration support from AbbVie, Bristol Myers Squibb, Chiesi, Dr Falk, Ferring, Gilead, Guidepoint, Intercept Pharmaceuticals, Janssen-Cilag, MSD, Norgine, Pfizer, Sandoz, Takeda and the RAH Research Fund. JA has served as a speaker, a consultant and an advisory board member for, and has received research funding from, Abbott, AbbVie, Allergan, Anatara, AstraZeneca, Bayer, Celgene, Falk, Ferring, Gilead, Hospira, Immunic, ImmunsanT, Janssen, MSD, Nestle, Progenity, Pfizer, Sandoz, Shire, Takeda, Vifor, RAH Research Fund, The Hospital Research Fund with all monies received by her department for research support. YKA reports grants from Janssen, during the conduct of the study; has received speaking and consulting fees from AbbVie, Bristol Myers Squibb, Celltrion, Chiesi, Dr Falk, Ferring, Janssen, Pfizer, Sandoz, Shire and Takeda; served on advisory boards for AbbVie, Bristol Myers Squibb, Chiesi, Janssen, NPS Medicine wise, Microba and received research and educational funding from Abbvie, Celltrion, Dr Falk, Janssen, Pfizer, Sandoz and Takeda. RVB has received grant/research support/speaker fees from AbbVie, Ferring, Janssen, Shire, Takeda, Bristol Myer Squibb and Emerge Health; and is a shareholder in Biomebank. SC declares advisory board participation, speaker fees, educational support and/or research support for Liverpool Hospital, South Western Sydney Local Health District (SWSLHD) Academic Unit or Crohn’s Colitis Cure from: AbbVie, Amgen, BMS, Celltrion, Chiesi, Eli-Lilly, Dr Falk, Ferring, Fresenius Kabi, Gilead, GSK, Janssen, MSD, Novartis, Organon, Pfizer, Sandoz, Takeda and non-pharmacological research support from Agency for Clinical Innovation, Gastroenterological Society of Australia, The Leona M and Harry B Helmsley Charitable Trust, Medical Research Future Fund, SWSLHD, Sydney Partnership for Health, Research and Enterprise (SPHERE). MG has served on the advisory board of Pfizer and has received speaker fees, research or travel grants from AbbVie, Celltrion, Dr Falk, Janssen, Pfizer, Pharmacosmos, Takeda. EKW declares speaker and consulting fees from AbbVie, BMS, Celltrion, Falk, Ferring, Janssen, Pfizer and research funding/support from AbbVie, Ferring, Janssen. JPS has received conference fees from Janssen, BMS, Takeda, educational grants from Pfizer, speaker fees from AbbVie, Takeda and Pfizer and an unrestricted grant from Tillots. PDC has served as a consultant, an advisory board member or a speaker for AbbVie, Baxter, Ferring, Janssen, Celltrion, Emerge Health, Shire and Takeda and received research support from Ferring, Shire, Janssen, AbbVie, and Takeda. MGW has received educational grants and speakers fees from AbbVie, Takeda and Ferring; travel grants from Pfizer; and has served on advisory boards for AbbVie. MPS has received educational grants or research support from Ferring, Orphan and Gilead; speakers fees from Janssen, AbbVie, Ferring, Takeda, Pfizer and Shire; and has served on advisory boards for Janssen, Takeda, Pfizer, Celgene, AbbVie, MSD, Emerge Health, Gilead and BMS. JM, PH, RBG, DC, MS, EC, LT, GH and AB declare no relevant competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Anti-interleukin 12/23 agents have shown greater durability in response compared with anti-tumor necrosis factor α agents. Data on the association between body composition (BC) or body mass index (BMI) and ustekinumab's therapeutic response is limited. We aimed to evaluate the impact of BC on time to failing standard doses of ustekinumab in patients with Crohn's disease (CD)., Method: Patients with CD aged 16 years and older from 2 tertiary centers were studied retrospectively. Included patients had abdominal imaging within 6 months of ustekinumab induction and were followed until April 30, 2022. An experienced abdominal radiologist blinded to the clinical information measured the area of visceral fat area and skeletal muscle area at the mid L3 vertebral level, with values corrected for height 2 to derive respective indices (visceral fat index [VFI], skeletal muscle index [SMI]) and the VFI:SMI ratio., Results: Ninety-nine patients met inclusion criteria. The mean age at ustekinumab induction was 46.6 (±1.6) years. The median BMI (interquartile range) was 26.5 (22.6-30.8). Twenty-four patients (24.2%) did not respond or lost response to standard doses of ustekinumab over the follow-up duration. A younger age (hazard ratio 0.96, 95% confidence interval 0.94-0.99, P = 0.01) and a VFI:SMI ratio >1.6 (hazard ratio 4.65, 95% confidence interval 1.73-12.45, P = 0.002) were both associated with a shorter time to failing ustekinumab at standard doses on multivariate analysis. BMI, notably, had no association with the primary outcome., Discussion: A high VFI:SMI ratio is associated with an increased risk of failing standard doses of ustekinumab. BC measurements derived from cross-sectional imaging at the start of ustekinumab therapy is a useful indicator for therapeutic durability., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Vedolizumab (VDZ), a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis (UC) patients., Aim: To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving remission., Methods: A retrospective review of Australian and Oxford, United Kingdom data for UC patients. Clinical response at 3 mo, endoscopic remission at 6 mo and clinical remission at 3, 6 and 12 mo were assessed. Cox regression models and Kaplan Meier curves were performed to assess the time to remission, time to failure and the covariates influencing them. Safety outcomes were recorded., Results: Three hundred and three UC patients from 14 centres in Australia and United Kingdom, [60% n = 182, anti-TNF naïve] were included. The clinical response was 79% at 3 mo with more Australian patients achieving clinical response compared to Oxford (83% vs 70% P = 0.01). Clinical remission for all patients was 56%, 62% and 60% at 3, 6 and 12 mo respectively. Anti-TNF naive patients were more likely to achieve remission than exposed patients at all the time points (3 mo 66% vs 40% P < 0.001, 6 mo 73% vs 46% P < 0.001, 12 mo 66% vs 51% P = 0.03). More Australian patients achieved endoscopic remission at 6 mo compared to Oxford (69% vs 43% P = 0.01). On multi-variate analysis, anti-TNF naïve patients were 1.8 (95%CI: 1.3-2.3) times more likely to achieve remission than anti-TNF exposed ( P < 0.001). 32 patients (11%) had colectomy by 12 mo., Conclusion: VDZ was safe and effective with 60% of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome., Competing Interests: Conflict-of-interest statement: All authors declare no conflict of interest related to this article., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Patients with inflammatory bowel disease who are refractory to standard therapies frequently require surgery. The long-term efficacy of tacrolimus in patients who fail standard immunosuppressive and antitumor necrosis factor α therapy is unknown., Methods: Thirty-five patients (11 Crohn's disease and 24 ulcerative colitis) with medication-resistant disease were treated with oral tacrolimus and reviewed retrospectively. Patients were commenced on tacrolimus 0.1 mg/kg/day, with a trough level targeted between 8 and 12 ng/mL. Clinical response or remission at 30 days, 90 days, and 1 year was assessed. The overall risk of requiring surgery and predictive factors were also assessed., Results: All patients had failed a thiopurine, 5 (14%) had also failed methotrexate, while 90% had a primary or secondary nonresponse, or an incomplete response, to an antitumor necrosis factor α agent. The proportions that achieved a clinical response at 30 days, 90 days, and 1 year was 65.7%, 60%, and 31.4%, respectively, whereas the corresponding proportions in remission were 40%, 37.1%, and 22.9%. The cumulative risk of requiring surgery was 40.4% at 1 year and 59.3% at 2 years with a median time to surgery of 22 months (range, 0.5-84 months). Patients who were steroid refractory, or dependent, before starting tacrolimus were more likely to have surgery (P = 0.006), whereas patients who were able to achieve or maintain a clinical response with tacrolimus by 90 days were less likely (P = 0.004)., Conclusions: Tacrolimus is able to induce a clinical response in a third and remission in a fifth of medically refractory patients with inflammatory bowel disease at 1 year. A 90-day therapeutic trial is worthwhile in difficult to treat patients.

Acute graft-versus-host disease following orthotopic liver transplantation is a rare but feared complication arising in 1% to 2% of cases with a dismal prognosis. It most often presents as fever, rash, and diarrhea with or without pancytopenia. Patients die from complications of marrow failure such as sepsis or bleeding. Because of its low incidence, there is no clear treatment protocol for this complication. Both increasing and withdrawing immunosuppression have been attempted with variable success. Although anti-tumor necrosis factor alpha therapy has been widely used for the treatment of steroid-resistant acute graft-versus-host disease in the hematopoietic stem cell transplant setting, there previously have been no reported cases of its use in liver transplantation. The aim of this report is to review a case of acute graft-versus-host disease and the use of etanercept to manage this complication. Etanercept has never previously been used in liver transplantation complicated by acute graft-versus-host disease. In the hematology literature, the success of its use is offset by significant rates of serious infectious (especially fungal) complications. However, preliminary results are encouraging and offer insight into its use as a potentially viable therapeutic option. We report the first successful use of etanercept in liver transplantation-associated graft-versus-host disease, albeit complicated by invasive aspergillosis, and recommend concurrent antifungal prophylaxis when the drug is used in this setting., (Copyright 2009 AASLD.)