Discontinuation of infliximab in patients with ulcerative colitis in remission (HAYABUSA): a multicentre, open-label, randomised controlled trial

Kobayashi T, Motoya S, Nakamura N, et al.

Lancet Gastroenterol Hepatol 2021;6:429–7. doi: 10.1016/S2468-1253(21)00062-5.

Rawen Kader © Rawen Kader

Introduction

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.

Tofacitinib as salvage therapy for 55 patients hospitalised with refractory severe ulcerative colitis: A GETAID cohort

Uzzan, M, Bresteau, C, Laharie, D, et al.

Aliment Pharmacol Ther. 2021;54:312– 9.

Aamir Saifuddin © Aamir Saifuddin

Introduction

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.

Johan Burisch © ECCO

Dear Y-ECCO Friends,

The year is slowly coming to an end and we can start looking forward to 2022 and hopefully returning to our normal, pre-COVID existence. Next year’s ECCO Congress will be among the first major scientific meetings within our specialty to have physical attendance. I’m sure you are all looking forward to meeting colleagues and friends in real life as much as I am. Don’t forget to sign up for our Basic Science Workshop!

Ann Driessen © ECCO

Inflammatory Bowel Disease is a longstanding recurrent inflammatory disorder that is most prevalent in Western countries but is increasing in Asiatic countries. The worldwide increase in the incidence of IBD, comprising Crohn’s Disease, Ulcerative Colitis and IBD unclassified, is having a significant impact on health care systems. Achievement of an optimal quality of care of IBD requires a multidisciplinary approach by different clinical disciplines, including pathology. Histopathology plays an essential role in the diagnosis and management of IBD. The pathologist excludes or confirms and subtypes IBD, assesses its activity and response to treatment and diagnoses preneoplastic lesions on endoscopic biopsies. Suboptimal sampling during endoscopy or insufficient clinical information, however, hampers the pathologist in making a diagnosis [1]. The main histological features of IBD are disturbance of the architecture and basal plasmacytosis, though a wide variety of disorders resemble IBD not only clinically and endoscopically but also histologically. Distinction between IBD and these mimics is essential as misdiagnosis results in delayed and incorrect management. Their differentiation is, however, not always straightforward and, in addition to a standard clinical examination, requires serology, imaging, endoscopy, histology and other investigations [2].

In the last decade the traditional management of Inflammatory Bowel Disease (IBD), based on clinically guided treatment intensification, has been revised and the so-called treat-to-target (T2T) approach, focusing on objective and scheduled measures to monitor intestinal inflammation, has been implemented in clinical practice, both in adults and in children. The general idea behind such tight monitoring is to prevent or block intestinal damage related to persistent and uncontrolled inflammation, and to avoid long-term complications.

Pär Myrelid © ECCO

Many technical innovations are facilitating the education process involved in training a skilled surgeon today. At the same time, this process is in many ways still a joint collaboration between a master and his/her apprentice, and will continue to be so. Fruitful training in any practical setting is based on trust, from both parties, in combination with application of the experience of the master in order to sort out any perioperative complications. Beyond acquisition of the necessary technical skill, becoming a surgeon requires the development of a sound understanding of when to operate and when not to, as well as the ability to choose the right surgical option. This is, of course, important in all surgical fields but it is perhaps especially true within the field of Inflammatory Bowel Disease (IBD).

Catherine Wall  © ECCO

The low-residue diet has been a short-term dietary strategy to help reduce the symptoms of active Crohn’s Disease and Ulcerative Colitis for at least the last half century. A longer term low-residue diet is also considered appropriate for a subset of patients with intestinal strictures [1], although the evidence to support this recommendation is limited and the type (fibrotic, inflammatory or both), severity (length of stricture and diameter of the bowel lumen), number of strictures and functional properties of certain foods likely impact tolerance of foods [1].

Petra Hartmann  © ECCO

One of the main goals of ECCO is to promote IBD research as well as to foster interaction and productive collaboration among European research groups working in the IBD field. To achieve this goal, ECCO continues to award Grants, Fellowships and Travel Awards. ECCO offers IBD Nurses across Europe the opportunity to apply for the N-ECCO Travel Award and the N-ECCO Research Grant.

Pascal Juillerat  © ECCO

Dear ECCO Members,

I hope you and your families are well and you are looking forward to spending the Christmas holidays together, as far as this is possible.

In case you missed or would like to re-watch some of the content from the ECCO’21 Virtual Congress that took place last summer – we kindly ask you to visit our e-Library, where all of the recordings can be found.

Naila Arebi  © ECCO

The level of confidence in evidence generated by research is reflected in various aspects of study design and underpins clinical guidelines in Inflammatory Bowel Disease (IBD). The quality of research study designs, each with inherent strengths and limitations, determines confidence in the results, and it is acknowledged that some ‘robust’ study designs may not be feasible in specific contexts [1, 2]. Experimental designs such as randomised controlled studies that are characterised by methodological rigour, may be unsuitable to study effectiveness owing to their weak external validity, which is attributable to their strict eligibility criteria. Reliance on complementary or alternative evidence from other study designs to address residual gaps in knowledge is not uncommon. Non-experimental observational study designs capture a more diverse population, albeit in a less stringent setting, resulting in several methodological limitations, including high risk of bias and unbalanced confounders [2]. The increasing digitalisation of medicine, in addition to accessible diverse sources of data, is partly responsible for recent intensification of interest in evidence generated by analysing data from observational studies with the purpose of offering new insights into the effectiveness and safety of interventions as well as understanding healthcare delivery and quality of care. The systematic analysis of data from multiple data sources outside a research setting is referred to as real-world studies (RWS), and its subsequent analysis and conclusions as real-world evidence (RWE) [3].