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].
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 [1]. 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.
The anti-tumour necrosis factor monoclonal antibody infliximab is one of the most widely used therapies for corticosteroid-refractory Ulcerative Colitis (UC). Long-term use of infliximab is associated with an increased risk of adverse events such as malignancies and infections, which is particularly concerning for those on concurrent immunosuppressive medications such as corticosteroids, thiopurines or calcineurin inhibitors [1–3]. With the number of patients with UC on long-term infliximab therapy continuing to rise, an important clinical question to address is whether these patients remain in remission upon discontinuing infliximab. Prospective studies have evaluated discontinuation of infliximab in patients with Crohn’s Disease, with deep (i.e. clinical, biological and endoscopic) remission thought to have a lower risk of relapse, but the evidence for patients with UC is limited to retrospective studies [4–6]. The HAYABUSA study aimed to address this issue with a randomised controlled trial (RCT) to evaluate discontinuing infliximab in patients with UC in remission.
Intensive drug therapy versus standard drug therapy for symptomatic intestinal Crohn's disease strictures (STRIDENT): an open-label, single-centre, randomised controlled trial
Crohn’s Disease (CD) is a chronic gastrointestinal inflammatory condition [1] that commonly causes strictures, with more than 50% of patients developing at least one stricture in the first decade after diagnosis [2]. Management options include biologics, endoscopic dilatation and surgery. Dilatation requires that the stricture be endoscopically accessible and medical therapy has limited benefit in fibrostenosing disease; therefore, surgery often remains the initial treatment of choice [3]. MRI and ultrasound can provide detailed assessment but cannot always definitively quantify active inflammation [4, 5].
This open label, randomised control trial was carried out at a specialist IBD unit in Australia with the aim of establishing whether medical therapy is an effective treatment of stricturing CD and, if so, whether intensive medical therapy is more effective than standard therapy. The primary end point was an improvement in the 14-day obstructive symptom score by one or more points compared to baseline at 12 months. Secondary outcomes included: improvement in the Crohn’s Disease Activity Index (CDAI), C-reactive protein (CRP), faecal calprotectin (FCP), stricture morphology on MRI, small bowel ultrasound (SBUS) or endoscopy, and correlation of serum adalimumab concentration with any improvement.
Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is often the preferred surgical intervention for patients with medically refractory Ulcerative Colitis [1]. A significant proportion of patients with IPAA develop pouch-related symptoms characterised by increased pouch emptying, urgency, bloody exudates and cramps. Such symptoms can occur secondary to inflammatory disorders, including idiopathic pouchitis, which affects up to 50% of patients, or other conditions such as pre-pouch ileitis [2]. Symptoms can also be due to non-inflammatory disorders, with irritable-pouch dysfunction accounting for more than a third of symptomatic patients.
The most commonly accepted disease activity index is the Pouchitis Disease Activity Index (PDAI), which combines symptoms, endoscopy findings and histology. A total PDAI 7 is considered diagnostic for pouchitis but is not specific [3].
The gold standard investigation is pouchoscopy, which allows endoscopic and histological assessment of the pouch, pre-pouch ileum and cuff [4]. However, it is an invasive and often uncomfortable procedure for patients. In some cases the alternative strategy of empirical antibiotic therapy for every symptomatic episode is adopted, but this comes with the risks associated with unnecessary antibiotic use.
In this cross-sectional study, Ardalan et al. sought to assess the role of non-invasive gastrointestinal ultrasound (GIUS) and faecal calprotectin (FCP) testing in the investigation of pouchitis.
The influence of proton pump inhibitor therapy on the outcome of infliximab therapy in inflammatory bowel disease: a patient-level meta-analysis of randomized controlled studies
The management of Inflammatory Bowel Disease (IBD) has evolved significantly over the last two decades [1, 2], as the development of biologic therapy has increased dramatically the rates of induction and prolonged maintenance of remission in patients with IBD. Infliximab (an anti-tumour necrosis factor) was the first biologic therapy to be approved for the treatment of IBD [3] and remains the biologic therapy with which clinicians have the most clinical experience [4].
Due to comorbidities, patients are frequently on other medications in addition to infliximab. How these other concomitant medications influence the response to infliximab therapy is largely unexplored.
Proton pump inhibitors (PPIs) are the first-line treatment for many digestive disorders such as gastro-oesophageal reflux disease (GORD), peptic ulcers, eosinophilic oesophagitis and dyspepsia [5]. PPIs are one of the most used family of medications in the United States, with more than 50 million prescriptions filled every year [6].
A few retrospective trials have attempted to investigate the impact of concomitant PPI therapy on response to infliximab in patients with IBD; however, these studies have suffered from the presence of many confounders, such as the lack of data on smoking status or the increased risk for gastroenteritis and C. difficile infection amongst patients treated with PPIs.
To increase the power to detect differential effects of PPI treatment on patients treated with infliximab in randomised trials and to allow adjustment for confounding factors, the investigators performed a patient-level meta-analysis of IBD randomised controlled clinical trials from the Yale Open Data Access (YODA) Framework.
Vedolizumab (VDZ) was the first biologic to be approved for Ulcerative Colitis (UC) and Crohn’s Disease (CD) after the age of anti-tumour necrosis factor antagonists (anti-TNF). The role of thiopurines in combination with anti-TNFs in the management of IBD is well recognised. However, the role for combination of VDZ with thiopurines is uncertain [1, 2]. This study aimed to investigate the comparative effectiveness of VDZ in combination with a thiopurine versus VDZ monotherapy in the management of both UC and CD.
Traditionally, treatment of Crohn’s Disease (CD) has focused on symptomatic, clinical and corticosteroid-free remission. However, more recent studies have shown that endoscopic remission is associated with more favourable patient long-term outcomes [1, 2]. It has been hypothesised that more intense treatment regimens may increase the likelihood of endoscopic remission in CD patients. Previous studies (such as that performed by the DIAMOND study group) have indicated that adalimumab trough levels are higher in CD patients who achieve an endoscopic response and mucosal healing at weeks 26 and 52 [3]. Further to that, the personalised anti-TNF therapy in Crohn's Disease study (PANTS) demonstrated that low drug levels were predictive of anti-tumour necrosis factor (anti-TNF) treatment failure [4].
Various methods of dose optimisation have been postulated, such as higher induction doses, therapeutic drug monitoring (TDM) to guide dose optimisation during the maintenance phase or a clinically adjusted (CA) dose optimisation strategy.
Many clinicians have anecdotally observed patients opting out of colonoscopies due to unpleasantness related to the procedure, and within Inflammatory Bowel Disease (IBD) populations a number of factors have been implicated in non-adherence, including logistics, health perceptions, stress and procedure problems (including discomfort) [1].
Prior studies have demonstrated patient preferences for propofol sedation over midazolam and fentanyl sedation for outpatient colonoscopy in general [2]. Furthermore, propofol has been shown to be safe, without severe adverse events or accidents [3], and nurse-administered propofol has specifically proven to be an efficient means of sedation for endoscopy in low-risk patients [4]. Nevertheless, this area has yet to be explored in the specific cohort of IBD patients.
Modern management of IBD requires the employment of ileocolonoscopy for diagnosis, as well as for the surveillance and guidance of future management. The investigators here looked to fill the aforementioned knowledge gap through design of a trial investigating the effectiveness of deep nurse-administered propofol sedation (NAPS), versus moderate midazolam and fentanyl sedation, as a means of improving patient satisfaction and future attitude towards colonoscopies.
Inflammatory Bowel Disease (IBD) is a long-term condition of the gut which is known to impact the quality of life and social functioning of those affected due to the chronic nature of symptoms. These factors, along with communication across the gut–brain axis, cause many patients to suffer from mental health disorders such as anxiety and depression [1]. Previously, the magnitude of these comorbidities had not been established, but recent studies [1, 2] have found the prevalence to be high: a third of all patients and a half of those with an active IBD flare have been found to suffer from anxiety, while depression has been found to affect a quarter of patients and a third of those with active symptoms.
Furthermore, compared with controls, patients with IBD and mental health disorders show increased use of healthcare resources (both primary care visits and emergency secondary care visits) and increased use of antidepressant and anxiolytic medications [2]. While antidepressant medications are commonly used to treat anxiety and depression in IBD [3], understanding of how effectively these treatments are prescribed remains limited, and this is particularly true regarding the adequacy of duration of treatment in this cohort.
This population-based study was performed in the United Kingdom and used data from the primary care setting that was routinely collected electronically in general practices as part of the Clinical Practice Research Datalink (CPRD). The authors looked to review the antidepressant prescribing in primary care for those diagnosed with IBD. They focused on the rate of antidepressant treatment initiation following IBD diagnosis, the duration of antidepressant treatment according to international guidelines, potential risks of inadequate antidepressant treatment duration and general trends in antidepressant prescribing.
