Approximately 25% of patients with Ulcerative Colitis (UC) require admission to hospital for acute severe (ASUC) or refractory disease, with one-third suffering from multiple episodes . The mainstay of initial anti-inflammatory treatment remains corticosteroids, following the seminal report from Truelove and Witts in the BMJ in 1955 [2, 3]. Here, 210 patients were randomised to standard care with oral cortisone or placebo. Significant benefit was demonstrated in the cortisone group, particularly in those at index presentation and those who had mild UC. At follow-up to 2 years, 21.5% had undergone surgery.
It is interesting that acute colectomy rates remain approximately 20% despite improvements in overall care and infliximab or ciclosporin ‘rescue’ therapy [1, 3]. The CONSTRUCT trial, reported in 2016, demonstrated no significant difference in the frequency of colectomy between these rescue medications, with surgery required in roughly 40% of steroid-refractory patients within one year.
Endoscopic grading of the severity of Ulcerative Colitis (UC) is a critical component of disease assessment and particularly important for guiding therapy. Despite the availability of numerous scoring systems, such as the Mayo Endoscopic Score (eMS) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), widespread use in routine clinical practice is often limited, primarily due to inter-observer variability and lack of training for standardised use [1,2].
Infection with the novel coronavirus SARS-CoV-2 leading to coronavirus disease-2019 (COVID-19) has a broad spectrum of clinical presentations and disease severity. A number of host and viral factors contribute to this heterogeneity in presentation and severity, including the host immune response . Given that immune-mediated inflammatory diseases (IMIDs) including Inflammatory Bowel Disease (IBD), are characterised by immune dysregulation and use of biologic or immunosuppressive therapies, COVID-19 presents a particular challenge.
Acute Severe Ulcerative Colitis (ASUC) is a medical emergency which affects about 25% of UC patients at least once in their lifetime . Corticosteroids are the mainstay of treatment for ASUC; however, 30%–40% of patients do not respond and eventually need medical rescue therapy or surgery .Medical rescue therapy (in the form of ciclosporin or infliximab) can be costly and its use can be limited by side effects. Therefore, there is a need for safe and low-cost therapy which can augment the effect of corticosteroids to induce and maintain remission.
Despite recent advances in medical therapy, patients with Crohn’s Disease may still suffer disease progression requiring surgery and hospitalisation. It is increasingly recognised that early effective therapy is associated with improved patient outcomes and there is growing emphasis on early intervention, treat to target and tight control (TC) approaches . The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) programme highlighted the importance of targetting deep remission, defined as resolution of symptoms and objective resolution of inflammation on endoscopy . The Effect of Tight Control Management on CD (CALM) study recently demonstrated that a TC approach in which therapy is escalated based on objective markers of inflammation [faecal calprotectin and C-reactive protein (CRP)], in addition to symptoms, is an effective strategy to achieve endoscopic and deep remission .
The advent of monoclonal antibody therapy has propelled the management of Inflammatory Bowel Disease firmly into the biologic era, with numerous biologic therapies now licensed or in various stages of development.
Anti-tumour necrosis factor (TNF) agents such as infliximab [1, 2], adalimumab [3, 4] and golimumab were the first biologics to be developed and have the greatest body of evidence for their effectiveness and safety in the treatment of Crohn’s Disease (CD) and Ulcerative Colitis (UC). The arrival of biosimilars has brought down costs and made treatment with anti-TNF more widespread, such that they are the most important first-line treatment option for moderate to severe IBD.
Crohn’s Disease is complicated by strictures in up to 30% of cases. Medical management with biologics is often suboptimal and surgical treatment is associated with postoperative complications and disease recurrence. Targeted therapy with endoscopic balloon dilatation (EBD) of strictures less than 5 cm has high rates of technical success (passage of endoscope through the stricture) but variable clinical success (relief of obstructive symptoms), with up to 25% of patients requiring surgery at one-year follow-up . Removable fully covered metal stents are safe for the treatment of refractory strictures but the risk of stent migration is high .
Fatigue is a common yet poorly understood manifestation of Inflammatory Bowel Disease (IBD) and can occur independently of disease activity. A prospective cohort study of 326 IBD patients initiating biologic therapy (with infliximab, vedolizumab or ustekinumab) demonstrated fatigue was prevalent at baseline (63%)1. Whilst fewer patients reported fatigue with treatment (70% at week 14, 61% at week 30 and 61% at week 54), a third continued to experience fatigue despite achieving clinical remission. This is supported by other studies, where fatigue prevalence in quiescent disease was as high as 36% in Ulcerative Colitis (UC) and 41% in Crohn’s disease (CD)2.
In the last decade, research on the human gut microbiome and its influence on health and disease has taken flight. This has strengthened the belief that the underlying pathogenesis of Inflammatory Bowel Disease (IBD) involves an altered immune response to characteristic shifts in the composition of the gut microbiome.
Serum biomarkers identify patients who will develop inflammatory bowel diseases up to 5 years before diagnosis
Torres J, Petralia F, Sato T, et al.
Inflammatory Bowel Disease is a chronic relapsing-remitting, immune-mediated condition with increasing prevalence globally . Despite novel agents targeting different disease pathways, the likelihood of achieving sustained clinical remission and mucosal healing remains low . One of the potential reasons may be that patients seek help and clinicians treat IBD once the disease is in its clinical phase. A sub-clinical phase of variable length may precede the symptoms that lead to a diagnosis and perhaps contribute to tissue damage which, once established, is difficult to reverse with currently available medical treatments.
In this study, Torres and colleagues set out to test the hypothesis that a pre-clinical phase of IBD may well be present and could be identified by proteomic markers .