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. 

Magali Svrcek © ECCO

Immune checkpoints (ICK) are downregulators of T cell immunity. Immune checkpoint inhibitors (ICKi), by blocking the co-inhibitory receptors on T cells to activate their cytotoxic immune function, have become a major therapeutic tool in oncology, notably for the treatment of metastatic melanoma, non-small cell lung carcinoma, renal cell carcinoma, urothelial carcinoma and mismatch repair (MMR) deficient/microsatellite-unstable tumours. In particular, therapeutic monoclonal antibodies have emerged against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), which primarily inhibits T cell activation, and programmed cell death 1 (PD-1), which limits the effector function of activated T cells in the periphery. Food and Drug Administration-approved ICKi include ipilimumab (CTLA-4 inhibitor), pembrolizumab and nivolumab (anti-PD-1) and atezolizumab (anti-PD-L1).

Johan Van Limbergen  © ECCO

Konstantinos Gerasimidis © ECCO

Johan Van Limbergen^1,2, Konstantinos Gerasimidis³

Crohn’s Disease (CD) is increasing in incidence worldwide [1]. In spite of increased use of immune suppression, which has markedly changed the need for in-hospital care, paediatric CD remains associated with considerable morbidity as well as increased mortality [2, 3]. The onset of disease in childhood and adolescence often interferes with growth and development, both physically and psychologically. In a subset of patients, the progressive nature of disease may be associated with a fibrotic phenotype that does not respond adequately to the currently available immune suppressive medications, yet use of these medications is still associated with increased risk of myelosuppression, opportunistic infections, immune-mediated phenomena and malignancy [2, 4–6]. 

Yves Panis © ECCO

As chair of the S-ECCO Committee, it is my pleasure to introduce a newly elected member for 2019, Pär Myrelid, who will stay for 3 years, up to February 2022. Thus, the current members of the S-ECCO Committee are: Michel Adamina (Winterthur, Switzerland) (who will be, after me, the next chair), Yves Panis (Clichy, France) (chair up to February 2020), Christianne Buskens (Amsterdam, who will stay up to February 2021), Hagit Tulchinsky (Tel Aviv, who will also stay up to February 2021) and Pär Myrelid.

Marjo Campmans- Kuijpers © ECCO

The importance of nutrition in IBD Management is increasingly recognised. Of course, the best evidence that nutrition deserves a place in IBD Treatment is the fact that exclusive enteral nutrition (EEN) is the primary treatment in children with active Crohn’s Disease (CD). In addition, some dietary patterns are associated with the outcomes in IBD, and recently it was shown that partial enteral nutrition, accompanied by a special CD exclusion diet, is as effective as EEN and brings into remission even those patients who fail on biologics.

Antonino Spinelli © ECCO

GuiCom has earned the reputation of being one of the busiest ECCO Committees. Looking at the number and importance of the ongoing projects in 2019, it is evident that this fame is well deserved: it is sufficient to mention the near completion of the new Crohn’s Disease (CD) Guidelines and the launch of the upcoming Ulcerative Colitis (UC) Guidelines.

Naila Arebi © ECCO

While the traditional role of epidemiology was the study of communicable diseases, it has evolved to a modern approach geared towards the study of the increasing incidence of non-communicable chronic diseases. Epidemiology may be defined as the collection of large sample sizes and the measurement of numerous variables from stored samples to facilitate estimation of disease risk over time, and may involve the development and use of new techniques to acquire dependent and independent variables [1]. Nevertheless, the traditional view of epidemiology remains embedded as the study of epidemics. In studying Inflammatory Bowel Disease (IBD) as an epidemic, several aspects were addressed at ECCO'19 Copenhagen Congress, including changes in the incidence/prevalence of IBD in different populations (countries), effects of therapy on surgical rates, the incidence of complications such as colorectal cancer, the impact of treatment patterns and findings in smaller sub-populations such as patients with elderly-onset and perianal Crohn’s Disease (CD). Although the modern definition carries a risk that studies will be conducted without a specific hypothesis thereby generating statistically significant observations of no clinical relevance nor benefit, the studies presented at ECCO 2019 addressed clinically important questions.

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].