Academia can generate high-quality paediatric data during off-label use of drugs: the example of the prospective multicentre VEDOKIDS study
Remarkably, of the numerous biologics approved in adults with IBD, only infliximab and adalimumab have been approved in children. The long delay between approval of new drugs in adults versus children leads to their extensive off-label use, in the absence of appropriate dosing and safety data. Prospective paediatric data regarding vedolizumab are limited to a small phase 2 study (n=88; HUBBLE trial) focusing on pharmacokinetics. A paediatric phase 3 trial is underway but its completion is long overdue, also since vedolizumab is easily accessible in most countries without the constraints of study protocols. With that challenge in mind, once vedolizumab received approval in adults we initiated a prospective cohort study to explore the effectiveness, dosing and safety of vedolizumab in children. The VEDOKIDS study was sponsored by ECCO, The Paediatric Porto group of ESPGHAN and Takeda. Explicit demographic, clinical and safety data were prospectively recorded, and serum was collected for drug levels and stool for faecal calprotectin.
A treat-to-target strategy and tight disease control may improve outcome in Crohn’s Disease (CD). However, this approach may necessitate long-term use of biological agents and immunosuppression. Combination therapy with anti-TNF and antimetabolite agents is now well established in this context. These drugs may be associated with long-term risks and elevated costs. It is important to establish whether treatment de-escalation, once deep remission has been achieved, is feasible and whether this strategy may improve safety profile and costs without jeopardising disease control.
The efficacy profile of IBD drugs is rapidly characterised by pivotal randomised controlled trials, but the safety profile of both old and new IBD drugs can only be established after years or decades of post-approval use. This is particularly true for relatively rare events, such as immunosuppression-related cancers. Clinical trials, meta-analyses and safety-dedicated registries are in general underpowered to evaluate the impact of IBD therapies on the risk of development of particular cancers. Data on clinical activity and phenotype of IBD are missing from nationwide administrative health databases, making it impossible to distinguish between the respective effects of IBD drugs and IBD activity on the risk of outcomes of particular interest, such as lymphomas.
It is with great pleasure and excitement that we announce the brand new ECCO Young Researcher Award 2022. This new ECCO Prize will be awarded to outstanding young researchers in recognition of their excellent contributions to basic and clinical science in the field of IBD. With this prize, ECCO strives to further support the visibility of exceptional young talents in IBD, acknowledge their achievements in the field and facilitate their ongoing and future research.
Paulo Kotze is Adjunct Senior Professor of Surgery at the Colorectal Surgery Unit at Cajuru University Hospital in Curitiba, Brazil. Working as a colorectal surgeon, he manages IBD with both the scalpel and medical therapies. He has been a key figure in ECCO for many years, having been a committee member of both S-ECCO and, more recently, EduCom. In the absence of the ECCO Congress, I spoke with him over Zoom about global ECCO, being an iconoclastic surgeon and his past as a bassist in the Brazilian punk band the Pinheads.
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.
For another year, unexpectedly, the Y-ECCO Basic Science Workshop had to be an online-only event, as the uncertainties related to the status of the pandemic caused the ECCO Congress 2022 to be changed into a virtual event. However, the workshop participants showed clearly that this did not affect their enthusiasm.
Sebastian Zeissig
Robin Dart
Gianluca Pellino