Treatment of inflammatory bowel disease with steroid-sparing medications is age-dependent - Results from a Danish nationwide cohort study, 2000-2018.

BACKGROUND: Paediatric-onset and elderly-onset inflammatory bowel disease (IBD) present unique treatment challenges. AIMS: We investigated treatment patterns following a first and second course of systemic steroids in paediatric- and elderly-onset IBD and compared them to adult-onset IBD. METHODS: All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 2000 and 2018 were identified through the Danish healthcare registries. Patients were divided into groups based on their age at diagnosis. Kaplan-Meier plots were prepared for medications and surgeries after diagnosis and after the first and second courses of systemic steroids. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariate Cox regression analysis for steroid-sparing medications. RESULTS: 1851 CD (13%) and 1687 (6%) UC patients were paediatric-onset, while 2952 (20%) CD and 5812 (23%) UC patients were elderly-onset. Paediatric-onset more frequently received immunomodulators [CD: HR: 1.64, CI: 1.52-1.77, UC: HR: 2.29, CI: 2.02-2.61] and biologics [CD: HR: 1.43, CI: 1.25-1.65, UC: HR: 1.27, CI: 0.99-1.64], while elderly-onset less frequently received immunomodulators [CD: HR: 0.39, CI: 0.35-0.44, UC: HR: 0.58, CI: 0.50-0.67] and biologics [CD: HR: 0.19, CI: 0.14-0.25, UC: HR: 0.36, CI: 0.27-0.48] compared to adult-onset age groups. After two courses of systemic steroids, elderly-onset still received less steroid-sparing medications. High frailty was associated with lower usage of medications for elderly-onset. CONCLUSION: There are significant differences in the use of steroid-sparing medication between age of onset, even after two courses with systemic steroids. High frailty could account for some of these differences in elderly-onset IBD.

Re-resection Rates and Disease Recurrence in Crohn's Disease - A Population-Based Study Using Individual-Level Patient Data.

BACKGROUND AND AIMS: Despite advances in the medical treatment of Crohn's disease (CD), many patients will still need bowel resections and face the subsequent risk of recurrence and re-resection. We describe contemporary re-resection rates and identify disease-modifying factors and risk factors for re-resection. METHODS: We conducted a retrospective, population-based, individual patient data cohort study covering 47.4% of the Danish population, including all CD patients who underwent a primary resection between 2010 and 2020. RESULTS: Among 631 primary resected patients, 24.5% underwent a second resection, and 5.3% a third. Re-resection rates after one, five, and 10 years were 12.6%, 22.4%, and 32.2%, respectively. Reasons for additional resections were mainly disease activity (57%) and stoma reversal (40%). Disease activity-driven re-resection rates after one, five, and 10 years were 3.6%, 10.1%, and 14.1%, respectively. Most stoma reversals occurred within one year (80%). The median time to recurrence was 11.0 months. Biologics started within one year of the first resection revealed protective effect against re-resection for stenotic and penetrating phenotypes. Prophylactic biologic therapy at primary ileocecal resection reduced disease recurrence and re-resection risk (HR 0.58, 95% CI (0.34-0.99), p=0.047). Risk factors for re-resection were location of resected bowel segments at the primary resection, disease location, disease behavior, smoking, and perianal disease. CONCLUSION: Re-resection rates, categorized by disease activity, are lower than those reported in other studies and are closely associated with disease phenotype and localization. Biological therapy may be disease-modifying for certain subgroups when initiated within one year of resection.

Analysis of Clinical Trial Screen Failures in Inflammatory Bowel Diseases (IBD): Real World Results from the International Organization for the study of IBD.

BACKGROUND: Recruitment for randomized controlled trials (RCTs) in IBD have substantially dropped over time. This study aimed to assess reasons why IBD patients are not included in sponsored multicenter phase IIb-III RCTs. METHODS: All IOIBD members (n=58) were invited to participate. We divided barriers to participation as follow: 1) reasons patients with active IBD were not deemed appropriate for a RCT; 2) reasons qualified patients did not wish to participate; 3) reasons for screen failure (SF) in patients agreeing to participate. We assess those in a 4-week prospective study including, consecutively, all patients with symptomatic disease for whom a treatment change was required. In addition, we performed a 6-month retrospective study to further evaluate reasons for SF. RESULTS: A total of 106 patients (60 male (56.6%), 63 Crohn's disease [CD] (59.4%)), from 10 centers across the world, were included in the prospective study. A RCT has not been proposed to 65 of them (mainly due to eligibility criteria). Of the 41 patients to whom a RCT was offered, 8 refused (mainly due to reluctance to receive placebo) and 28 agreed to participate. Among these 28 patients, 5 failed their screening and 23 were finally included in a RCT. A total of 107 patients (61 male (57%), 67 CD (62.6%)), from 13 centers worldwide, were included in our retrospective study of SFs. The main reason was insufficient disease activity. CONCLUSION: This first multicenter study analyzing reasons for non-enrollment in IBD RCTs shown that we lose patients at each step. Eligibility criteria, the risk of placebo assignment and insufficient disease activity were part of the main barriers.

Leclercia adecarboxylata: a case report and literature review of 74 cases demonstrating its pathogenicity in immunocompromised patients.

Leclercia adecarboxylata is a Gram-negative bacterium belonging to the family Enterobacteriaceae. It has been described as an emerging human pathogen with the potential to cause severe infection in immunocompromised patients. The aim of this study was to describe a clinical case of infection with L. adecarboxylata and give a review of previous reports on infection. We report the presence of L. adecarboxylata in a patient initially admitted to our hospital for a lung transplant. She had diarrhoea, urinary tract infection and pneumonia caused by L. adecarboxylata. The isolate was resistant to trimethoprim-sulfamethoxazole and susceptible to 15 other antibiotics tested. The literature search for previous reports of infection with L. adecarboxylata resulted in 61 publications describing 74 cases. Bacteremia and wound infections were most often described, and only a few cases were fatal. L. adecarboxylata was most often found as a monomicrobial infection in immunocompromised patients, and as part of a polymicrobial infection in immunocompetent patients. The previously described isolates showed a high susceptibility to antibiotics, and treatment was efficient in most cases. Due to similarities in metabolic products, L. adecarboxylata might have been mistaken as Escherichia spp., but with new identification methods such as MALDI-TOF MS, it is possible to obtain a certain identification.