No association between pseudopolyps and colorectal neoplasia in patients with inflammatory bowel diseases

Mahmoud R, Shah SC, Ten Hove JR, Torres J, Mooiweer E, Castaneda D, Glass J, Elman J, Kumar A, Axelrad J, Ullman T, Colombel JF, Oldenburg B, Itzkowitz SH; Dutch Initiative on Crohn and Colitis

Gastroenterology. 2019;156:1333–44.e3.

Introduction

Sailish Honap © Sailish Honap

Patients with Inflammatory Bowel Disease (IBD) are at an increased risk of developing high-grade dysplasia and colorectal carcinoma [1, 2]. The risk of carcinogenesis, driven by chronic inflammation, increases with several factors, including duration and anatomic extent of colitis, family history and the presence of primary sclerosing cholangitis (PSC). European clinical guidelines for colonoscopy surveillance in this high-risk cancer population also suggest a shorter surveillance interval for those with post-inflammatory polyps (PIPs), also known as pseudopolyps [3–5]. PIPs are a common finding, more so in Ulcerative Colitis (UC) than in Crohn’s Disease, and are formed after alternating cycles of inflammation and regeneration of the epithelial mucosa. However, data are conflicting and evidence is lacking in this field as previous case control studies have reported up to a 2.5-fold increased risk [6, 7] whereas a more recent cohort study showed no significant association between PIPs and colorectal neoplasia (CRN) [8]. The authors of this study aimed to use a large cohort study to further define the risk of CRN and PIPs in patients with Inflammatory Bowel Disease.  

Crohn’s Disease exclusion diet plus partial enteral nutrition induces sustained remission in a randomized controlled trial

Levine A, Wine E, Assa A, Boneh RS, Shaoul R, Kori M, Cohen S, Peleg S, Shamaly H, On A, Millman P, Abramas L, Ziv-Baran T, Grant S, Abitbol G, Dunn KA, Bielawski JP, Van Limbergen J

Gastroenterology. 2019;157:440–50.

Introduction

Paul Harrow © Paul Harrow

Exclusive enteral nutrition (EEN) is a safe and effective induction treatment for Crohn’s Disease (CD). It is recommended as first-line induction therapy in children and adolescents [1]. However, enteral nutrition is less well tolerated than other options like corticosteroids. A recent meta-analysis found three times as many patients withdrew from enteral nutrition therapy compared to corticosteroids even in the supported setting of clinical trials [2]. There is a clear need for a more acceptable dietary intervention. However, our understanding of the role of diet in CD is incomplete and to date specific diets have not been proven to induce remission. 

Ustekinumab exposure-outcome analysis in Crohn’s Disease only in part explains limited endoscopic remission rates

Verstockt B, Dreesen E, Noman M, Outtier A, Van den Berghe N, Aerden I, Compernolle G, Van Assche G, Gils A, Vermeire S, Ferrante M

J Crohns Colitis. 2019;13:864–72.

Introduction

Samantha Campbell © Samantha Campbell

Ustekinumab is licenced to treat moderate-severe Crohn’s Disease (CD) [1]. Ustekinumab induction is administered via intravenous (IV) infusion at a dose of 6 mg/kg at week 0, followed by a subcutaneous (SC) maintenance injection of 90 mg at week 8.

The UNITI programme demonstrated that ustekinumab can induce and maintain clinical remission. However, there is a paucity of real-life data in patients with CD receiving the mentioned IV induction and SC maintenance dosing of ustekinumab. Real-life data on therapeutic drug monitoring and biomarkers, such as faecal calprotectin, remain a relatively unexplored area with ustekinumab, with discrepancies in the literature [2, 3]. . 

Rates and characteristics of postcolonoscopy colorectal cancer in the Swedish IBD population: What are the differences from a non-IBD population?

Stjärngrim J, Ekbom A, Hammar U, Hultcrantz R, Forsberg AM

Gut 2018 Dec 15; doi: 10.1136/gutjnl-2018-316651

Introduction

Rohit Rao  © Rohit Rao

Individuals with IBD have an increased risk of colorectal cancer (CRC) [1, 2]. In an effort to address this, societal guidelines recommend surveillance colonoscopy 8–10 years after diagnosis and at varying intervals thereafter, depending on risk [3, 4]. A 2017 Cochrane systematic review [5] demonstrated a benefit in this strategy, noting reductions in the development of both CRC and the rate of CRC‐associated death. Despite this, dysplasia detection is challenging and CRC still accounts for 10%–15% of all IBD deaths [6, 7]. Of further concern is the reported increased rate of post-colonoscopy colorectal cancer (PCCRC) in IBD. 

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.

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.