Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn’s disease: A prospective, multicentre, cohort study

Kennedy NA, Heap GA, Green HD, Hamilton B, Bewshea C, Walker GJ, Thomas A, Nice R, Perry MH, Bouri S, Chanchlani N, Heerasing NM, Hendy P, Lin S, Gaya DR, Cummings JRF, Selinger CP, Lees CW, Hart AL, Parkes M, Sebastian S, Mansfield JC, Irving PM, Lindsay J, Russell RK, McDonald TJ, McGovern D, Goodhand JR, Ahmad T, UK Inflammatory Bowel Disease Pharmacogenetics Study Group*

Lancet Gastroenterol Hepatol. 2019;4:341–53

Introduction

Misha Kabir  © Misha Kabir

The anti-TNF monoclonal antibodies infliximab and adalimumab have been integral to the management of Crohn’s Disease over the past two decades. However, primary non-response and secondary loss of response in the first year of treatment remain common, at 10%–40% [1–3] and 23%–46% [4] respectively. Immunogenicity has been implicated as an important predictive factor for anti-TNF therapy failure. However, target-to-treat drug and anti-drug antibody concentrations have not yet been validated in an adequately powered prospective study. The Personalised Anti-TNF Therapy in Crohn’s Disease Study (PANTS) aimed to investigate the factors that predict primary non-response, non-remission and adverse events with anti-TNF therapy in luminal Crohn’s Disease.

Early combined immunosuppression may be effective and safe in older patients with Crohn’s disease: post hoc analysis of REACT

Singh S, Stitt LW, Zou G, et al.

Aliment Pharmacol Ther. 2019;49:1188–94.

Introduction

Georgina Cunningham  © Georgina Cunningham

Due to the ageing population and the chronicity of the disease, increasing numbers of patients with Inflammatory Bowel Disease (IBD) are now over the age of 60 [1]. The management of IBD in this group poses some challenges, mainly centered on the balance between risk of immunosuppression and the burden of active disease [2]. Although older IBD patients usually display a more indolent disease course, they are more likely to be hospitalised and have higher in-hospital mortality than their younger counterparts [3]. There is no doubt that there is room for improvement in our management of IBD in elderly patients, and guidance is needed to help physicians decide whether more aggressive treatment strategies, widely accepted in certain younger IBD patients [4], are also warranted in this cohort, and especially those at high risk of disease complications.

Dominik Bettenworth © ECCO

Dear Y-ECCO Friends,

One of the main tasks of the Young ECCO Committee (Y-ECCO) is to offer Y-ECCO Members opportunities to expand their scientific skills and develop their own research projects. Following the last Y-ECCO Basic Science Workshop in Copenhagen, which was a great success in terms of attendance and participant feedback, plans for the 6th Y-ECCO Basic Science Workshop at the 15th Congress of ECCO in Vienna 2020 are already in full swing. The potential for the successful establishment of intestinal organoids will substantially expand the basic research on Inflammatory Bowel Diseases (IBD). In addition, experimental research should always focus on an effective translation of experimental results into the clinic in order to improve the treatment of our IBD patients in the long term. Therefore, organoids and translational basic science research will be the two main topics of the 6th Y-ECCO Basic Science Workshop. Fortunately, we were able to expand the structure of the workshop so that three awardees of the ECCO Research Fellowships Programme will present their results at the workshop and will also be available to answer all your questions regarding the pros and cons of a fellowship. 

Charlotte Hedin © ECCO

Our interviewee for this Issue is the current Director of the Center for Clinical Research and Prevention at Bispebjerg and Frederiksberg Hospital in Copenhagen, Denmark. She started her medical training at Herlev University Hospital in Copenhagen, but early in her career the lure of research called and she embarked on a career in epidemiology with a particular focus on IBD and cancer risk. To date she has more than 130 publications listed on PubMed, of which many are highly cited and over 70 are first or last author contributions. She has received many awards for her research and is frequently invited to present her data at international meetings and congresses. Professor Tine Jess, welcome to the Interview Corner.

Optimised infliximab monotherapy is as effective as optimised combination therapy, but is associated with higher drug consumption in Inflammatory Bowel Disease

Drobne D, Kurent T, Golob S, Švegl P, Rajar P, Hanžel J, Koželj M, Novak G, Smrekar N, Ferkolj I, Štabuc B

Aliment Pharmacol Ther. 2019;49:880–9

Aravind Gokul Tamilarasan  © Aravind Gokul Tamilarasan

Introduction

Since the publication of the landmark SONIC trial in 2010 [1], the use of combination biologic–immunomodulator therapy has been considered best standard practice for patients with Inflammatory Bowel Disease (IBD) who have failed topical therapies or immunomodulators (thiopurines or methotrexate). More recently, real-world data from the PANTS (Personalised anti-TNF therapy in Crohn’s Disease) study demonstrated the benefit of combination therapy (particularly for infliximab) in the form of higher week 54 remission rates and prevention of immunogenicity [2]. Notably, the week 54 remission rates were independent of infliximab trough levels or immunogenicity status, suggesting additional benefits apart from improving the pharmacokinetics of infliximab. This study aimed to provide further real-world data on the effect of combination therapy on clinical and pharmacokinetic outcomes.

Risankizumab in patients with moderate to severe Crohn's Disease: An open-label extension study

Feagan BG, Panés J, Ferrante M, Kaser A, D'Haens GR, Sandborn WJ, Louis E, Neurath MF, Franchimont D, Dewit O, Seidler U, Kim KJ, Selinger C, Padula SJ, Herichova I, Robinson AM, Wallace K, Zhao J, Minocha M, Othman AA, Soaita A, Visvanathan S, Hall DB, Böcher WO

Lancet Gastroenterol Hepatol. 2018;3:671–80. DOI: https://doi.org/10.1016/S2468-1253(18)30233-4   

James Gauci  © James Gauci

Introduction

Management of Crohn’s Disease involves the suppression of inflammation through administration of immunosuppressive drugs. While conventional therapies such as corticosteroids and thiopurines exert a broad effect on the immune system, the advent of biological agents has allowed for selective targeting of cytokines and integrins.

Unfortunately, a third of patients treated with tumour necrosis factor (TNF) antagonists demonstrate a primary non-response, with another third developing either secondary failure or intolerance. These patients will then have a lower chance of responding to treatment with other TNF antagonists or with the integrin antagonist vedolizumab.

Serum Concentration of 7α-hydroxy-4-cholesten-3-one Are Associated With Bile Acid Diarrhea in Patients With Crohn's Disease

Battat R, Duijvestein M, Vande Casteele N, Singh S, Dulai PS, Valasek MA, Mimms L, McFarland L, Hester KD, Renshaw M, Jain A, Sandborn WJ, Boland BS

Clin Gastroenterol Hepatol. 2018 Nov 15. doi:10.1016/j.cgh.2018.11.012    

Ivan Lyutakov  © Ivan Lyutakov

Introduction

Inflammatory Bowel Disease (IBD) comprises a heterogeneous group of chronic inflammatory disorders with two main conditions, Crohn’s Disease (CD) and Ulcerative Colitis (UC) [1]. Bile acid malabsorption (BAM) and bile acid diarrhoea (BAD) have been recognised to be a common cause of chronic diarrhoea, and this recognition has led to the initiation of a search for new screening tests (biomarkers). BAM is one of the mechanisms leading to microscopic colitis, a key factor in the pathogenesis of irritable bowel syndrome-diarrhoea, and molecular mechanisms of BAM are found in IBD patients with or without involvement of the terminal ileum. BAM/BAD is more frequently found in CD than in UC, and the obvious aetiology for BAM in CD is either ileal resection or ileal disease [2]. The pathophysiology of diarrhoea in CD is multifactorial but there are two key factors, colonic water and electrolyte absorption, which can be impaired directly by colonic inflammation or indirectly by increased concentrations of bile acids having secretory effects, referred to as BAD [3].

Mark Samaan  © ECCO

Dear Y-ECCO Friends,

A warm welcome to the Y-ECCO Literature Review section, where you will find a summary and discussion of cutting-edge clinical trials as well as basic science studies in the field of IBD. 

If you are a Y-ECCO Member and you are looking for an opportunity to get actively involved in ECCO and gain some visibility, contribute your article to the Y-ECCO Literature Review corner, together with a short self-description and your picture.

Johan Burisch © ECCO

Every two years, Y-ECCO arranges a workshop addressing topics about career and skill development for young researchers and physicians. We thereby aim to address important topics that are not fully covered during the rest of the ECCO Congress. This year the workshop took place for the 11^th time, with the overall topic being modern career-enhancing skills. 

Nuha Yassin © ECCO

Dear Y-ECCO Friends,

We hope you are all well and that you enjoyed the ECCO Congress. We certainly did, and we were very pleased to meet many new members at the Y-ECCO Basic Science Workshop as well as to catch up with familiar faces. This year our workshop was over-subscribed, and the room was jam-packed. Our participants consisted of a mixture of basic scientists, clinicians, clinician scientists, nurses, trainees and senior members. We are delighted that our Basic Science Workshop appeals to everyone and caters for many needs.