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.
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.
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.
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.
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.
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.
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 [1]. 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 [1]. Corticosteroids are the mainstay of treatment for ASUC; however, 30%–40% of patients do not respond and eventually need medical rescue therapy or surgery [2].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 [1]. 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 [2]. 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 [3].
