Perianal Fistulizing Crohn's Disease: Utilizing the TOpClass Classification in Clinical Practice to Provide Targeted Individualized Care.

BACKGROUND & AIMS: Perianal fistulation is a challenging phenotype of Crohn's disease, with significant impact on quality of life. Historically, fistulae have been classified anatomically in relation to the sphincter complex, and management guidelines have been generalized, with lack of attention to the clinical heterogenicity seen. The recent 'TOpClass classification system' for perianal fistulizing Crohn's disease (PFCD) addresses this issue, and classifies patients into defined groups, which provide a focus for fistula management that aligns with disease characteristics and patient goals. In this article, we discuss the clinical applicability of the TOpClass model and provide direction on its use in clinical practice. METHODS: An international group of perianal clinicians participated in an expert consensus to define how the TOpClass system can be incorporated into real-life practice. This included gastroenterologists, inflammatory bowel disease surgeons, and radiologists specialized in PFCD. The process was informed by the multi-disciplinary team management of 8 high-volume fistula centres in North America, Europe, and Australia. RESULTS: The process produced position statements to accompany the classification system and guide PFCD management. The statements range from the management of patients with quiescent perianal disease to those with severe PFCD requiring diverting-ostomy and/or proctectomy. The optimization of medical therapies, as well as the use of surgery, in fistula closure and symptom management is explored across each classification group. CONCLUSION: This article provides an overview of the system's use in clinical practice. It aims to enable clinicians to have a pragmatic and patient goal-centered approach to medical and surgical management options for individual patients with PFCD.

Effectiveness, safety, and drug sustainability of biologics in elderly patients with inflammatory bowel disease: A retrospective study.

BACKGROUND: Biologic therapy resulted in a significant positive impact on the management of inflammatory bowel disease (IBD) however data on the efficacy and side effects of these therapies in the elderly is scant. AIM: To evaluate retrospectively the drug sustainability, effectiveness, and safety of the biologic therapies in the elderly IBD population. METHODS: Consecutive elderly (≥ 60 years old) IBD patients, treated with biologics [infliximab (IFX), adalimumab (ADAL), vedolizumab (VDZ), ustekinumab (UST)] followed at the McGill University Inflammatory Bowel Diseases Center were included between January 2000 and 2020. Efficacy was measured by clinical scores at 3, 6-9 and 12-18 mo after initiation of the biologic therapy. Patients completing induction therapy were included. Adverse events (AEs) or serious AE were collected during and within three months of stopping of the biologic therapy. RESULTS: We identified a total of 147 elderly patients with IBD treated with biologicals during the study period, including 109 with Crohn's disease and 38 with ulcerative colitis. Patients received the following biologicals: IFX (28.5%), ADAL (38.7%), VDZ (15.6%), UST (17%). The mean duration of biologic treatment was 157.5 (SD = 148) wk. Parallel steroid therapy was given in 34% at baseline, 19% at 3 mo, 16.3% at 6-9 mo and 6.5% at 12-18 mo. The remission rates at 3, 6-9 and 12-18 mo were not significantly different among biological therapies. Kaplan-Meyer analysis did not show statistical difference for drug sustainability (P = 0.195), time to adverse event (P = 0.158) or infection rates (P = 0.973) between the four biologics studied. The most common AEs that led to drug discontinuation were loss of response, infusion/injection reaction and infection. CONCLUSION: Current biologics were not different regarding drug sustainability, effectiveness, and safety in the elderly IBD population. Therefore, we are not able to suggest a preferred sequencing order among biologicals.

Classifying perianal fistulising Crohn's disease: an expert consensus to guide decision-making in daily practice and clinical trials.

Perianal fistulising Crohn's disease is an aggressive disease phenotype that can have a substantial detrimental impact on patients' quality of life. Current biological understanding of perianal fistulising Crohn's disease remains inadequate and previous classification systems have not provided clear guidance on therapy in clinical practice nor on defining patient cohorts within clinical trials. We propose a new classification system for perianal fistulising Crohn's disease that was developed through a modified nominal group technique expert consensus process. The classification identifies four groups of patients. Key elements include stratification according to disease severity as well as disease outcome; synchronisation of patient and clinician goals in decision making, with a proactive, combined medical and surgical approach, on a treat to patient goal basis; and identification of indications for curative fistula treatment, diverting ostomy, and proctectomy. The new classification retains an element of flexibility, in which patients can cycle through different classes over time. Furthermore, with each specific class comes a paired treatment strategy suggestion and description of clinical trial suitability. The proposed classification system is the first of its kind and is an important step towards tailored standardisation of clinical practice and research in patients with perianal fistulising Crohn's disease.

Ulcerative colitis: an update.

Ulcerative colitis is a relapsing and remitting disease that is increasing in incidence and prevalence. Management aims to achieve rapid resolution of symptoms, mucosal healing and improvement in a patient's quality of life. 5-aminosalicylate acid medications remain the first-line treatment for mild to moderate disease. In the event of suboptimal response to these medications, escalation to immunosuppressive medications and biologics may be necessary. Importantly, despite best medical therapy, surgery may be required in a proportion of patients. The future will likely see an array of new therapeutic options for those with ulcerative colitis with the potential for a more personalised treatment approach.

IgG4-associated autoimmune hepatitis and cholangitis: A relatively novel entity to consider in cases of seronegative autoimmune hepatitis.

A 49-year-old woman with no inflammatory bowel disease history presented to our clinic with abnormal liver function tests and right upper quadrant abdominal pain. Blood tests revealed a mixed pattern of liver injury. Abdominal magnetic resonance imaging demonstrated hepatomegaly with periportal edema and hyper-enhancing bile ducts without any sign of biliary obstruction or stricturing. Screening for viral hepatitis and autoimmune liver diseases was negative. An elevated immunoglobulin G (IgG) level suggested the possibility of autoimmune hepatitis (AIH), and a biopsy confirmed the presence of severe interface hepatitis with necrotic areas and focal lymphoid nodular formation. IgG4 staining revealed marked IgG4-positive plasma cell infiltration. A diagnosis of IgG4-associated seronegative AIH was made, and the patient was started on prednisone and azathioprine, with rapid resolution of the enzyme abnormalities. This clinical vignette highlights the potential challenges in establishing a diagnosis of IgG4-associated AIH and cholangitis, as demonstrated by the importance of confirmatory histopathology. Clinicians should maintain a high index of suspicion when confronted with a mixed pattern of liver injury with elevated immunoglobulins but seronegative autoimmune markers.

Are we addressing the top 10 research priorities in IBD?

BACKGROUND: Since publication of the top 10 research priorities in inflammatory bowel disease (IBD) based on the James Lind Alliance Priority Setting Partnership, the question remains whether this has influenced the IBD-research landscape. This study aimed to create an overview of the current distribution of research interests of trials in the UK. METHODS: The ClinicalTrials.gov database and European Union Clinical Trials Register were screened for clinical trials set up from 9 August 2016 to 16 November 2019 in the UK involving adult patients with IBD. RESULTS: Of 20 non-industry-sponsored studies, a quarter investigated treatment strategies considering efficacy, safety and cost-effectiveness (priority 1). Four evaluated the role of diet (priorities 3 and 7). Development/assessment of biomarkers for patient stratification (priority 2) and fatigue (priority 8) were subject of three studies. IBD-related pain and control of diarrhoea/incontinence were each subject of 2 studies (priorities 4 and 6). The effect of gut microbiota (priority 10) and optimal strategy for perianal Crohn's disease (priority 5) was the focus of 2 studies each. One study evaluated surgery for terminal ileal Crohn's disease (priority 9). Of 63 industry-sponsored studies, 59 focused on priority 1. CONCLUSIONS: This study presents an impression of the breadth of the IBD-research landscape in the UK, in light of the top 10 research priorities published in 2016. Optimal treatment strategy has been the most studied research priority by academic and industry-sponsored trials. Fewer studies focused on patient-reported outcomes. It remains debatable to what extent the current research landscape adequately represents all stakeholders' viewpoints on needs for expanded knowledge in IBD, particularly the patients' perspective.

The Microbiome as a Therapy in Pouchitis and Ulcerative Colitis.

The gut microbiome has been implicated in a range of diseases and there is a rapidly growing understanding of this ecosystem's importance in inflammatory bowel disease. We are yet to identify a single microbe that causes either ulcerative colitis (UC) or pouchitis, however, reduced microbiome diversity is increasingly recognised in active UC. Manipulating the gut microbiome through dietary interventions, prebiotic and probiotic compounds and faecal microbiota transplantation may expand the therapeutic landscape in UC. Specific diets, such as the Mediterranean diet or diet rich in omega-3 fatty acids, may reduce intestinal inflammation or potentially reduce the risk of incident UC. This review summarises our knowledge of gut microbiome therapies in UC and pouchitis.

Elderly patients with inflammatory bowel disease: Updated review of the therapeutic landscape.

High-quality data remains scarce in terms of optimal management strategies in the elderly inflammatory bowel disease (IBD) population. Indeed, available trials have been mostly retrospective, of small sample size, likely owing to under-representation of such a population in the major randomized controlled trials. However, in the last five years, there has been a steady increase in the number of published trials, helping clarify the estimated benefits and toxicity of the existing IBD armamentarium. In the Everhov trial, prescription strategies were recorded over an average follow-up of 4.2 years. A minority of elderly IBD patients (1%-3%) were treated with biologics within the five years following diagnosis, whilst almost a quarter of these patients were receiving corticosteroid therapy at year five of follow-up, despite its multiple toxicities. The low use of biologic agents in real-life settings likely stems from limited data suggesting lower efficacy and higher toxicity. This minireview will aim to highlight current outcome measurements as it portends the elderly IBD patient, as well as summarize the available therapeutic strategies in view of a growing body of evidence.

Examination of Physicians' Perception of the Indications of Colorectal Stents in the Management of Malignant Large Bowel Obstruction: A Provincial Survey.

Introduction. Data are conflicting when assessing indications for colorectal self-expandable metallic stents (SEMS) in managing acute malignant large bowel obstruction (MLO). In November 2014, European and American Societies published guidelines to aid in understanding which patients might benefit from colorectal stenting. Yet, there remain marked disparities in clinical practice. Methods. A web-based survey was sent to Gastroenterologists and Surgical Specialists across Quebec to assess physicians' knowledge and adherence to the indications for colonic SEMS placement in the management of MLO using eight clinical scenarios. Results. Out of 112 respondents, 74% preferred surgical intervention in young, healthy individuals with MLO. Advanced age and comorbidities motivated 56.3% (95% CI 47.1-65.5%) of participants to opt for SEMS placement. In palliative settings of patients undergoing chemotherapy including bevacizumab, a minority of respondents followed guidelines, 12.5% (95% CI 6.4-18.6%) for young patients and 25.0% for elderly patients (95% CI 17.0-33.0%). The pooled overall adherence to guidelines was 50.4% (95% CI 40.7-59.3%). Conclusion. This survey suggests that guidelines recommendations are not being implemented by at least half of specialists involved in the care of patients with MLO. Future studies should attempt to identify possible barriers responsible for this impaired knowledge translation and tailored educational initiatives planned accordingly.