Erwin Dreesen © ECCO

Targeting endoscopic outcomes through combined pharmacokinetic and pharmacodynamic monitoring of infliximab therapy in patients with Crohn’s Disease

In the multicentre, randomised, controlled TAILORIX trial, it was not possible to show a benefit of infliximab dose escalation based on a combination of pharmacokinetic monitoring (i.e. serum concentrations of infliximab) and pharmacodynamic monitoring (i.e. symptoms and biomarker) as compared to dose escalation based on symptoms alone [1]. However, infliximab dose escalations only commenced after the induction regimen. In the current post hoc pharmacokinetic–pharmacodynamic analysis of TAILORIX, we examined the roles of pharmacokinetic and pharmacodynamic monitoring during infliximab induction and maintenance therapy for targeting endoscopic outcomes [2].

Proactive adalimumab trough measurement is associated with improved treatment outcomes in children with Crohn’s Disease: The PAILOT randomised controlled trial

Amit Assa © ECCO

Loss of response (LOR) during anti-TNF treatment for Crohn's Disease (CD) is commonly approached through the measurement of trough concentration (TC) and anti-drug antibodies, with subsequent modification of treatment (reactive therapeutic drug measurement, TDM). It is appealing to speculate that tailored treatment based on routine TC and antibody measurements (proactive TDM) may assist in sustaining adequate drug levels and thus in improving efficacy and preventing the evolution of anti-drug antibodies. Nevertheless, two randomised controlled trials, the TAXIT [1] and the TAILORIX [2], have failed to demonstrate superiority of level-based over clinically based adjustment of infliximab treatment. To date, there are no prospective studies comparing proactive vs reactive TDM in paediatric CD nor are there any studies evaluating the proactive approach among adults or children treated with adalimumab. Hence, we aimed to investigate the effect of proactive drug monitoring-based treatment, in comparison with clinical and biologic-based monitoring of disease activity in children with CD treated with adalimumab.

Janneke van der Woude © ECCO

During the ECCO’19 Copenhagen Congress the Scientific Committee cordially welcomed Marc Ferrante as a new member.

Marc Ferrante has been an individual member of ECCO since 2008 and has contributed to several ECCO Activities and Initiatives. He was one of the Y-ECCO Founders and Y-ECCO Chairs. His career in ECCO continued in 2015 with a position on ClinCom, and he subsequently became chair of this committee in 2017. 

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.