At the ECCO Congress 2020, 15 representatives from 11 countries gathered to discuss the ECCO GuiCom Topical Review on Refractory IBD. This project is being led by Tim Raine (United Kingdom) and Garret Cullen (Ireland). The aim of the project is to bring together evidence and recommendations on how to approach the patient with active Crohn’s Disease (CD) or Ulcerative Colitis (UC) who has not responded to all licensed treatment options.
Change is the cornerstone of the innovation that drives science forward. Of many expressions that capture change, ‘out with the old, in with the new’ expresses well what occurs when the composition of committees alters. As members step down and new members take their place, fresh ideas and different perspectives are heard, leading to renewed enthusiasm that will drive the agenda for the future. Against this backdrop, EpiCom welcomes Sophie Restellini while bidding a sad farewell to Marieke Pierik.
Top-down infliximab is superior to step-up in children with moderate-to-severe Crohn’s Disease
In newly diagnosed paediatric patients with Crohn’s Disease (CD), rapid disease control is desirable, but this outcome is not always achieved with current treatment strategies [1]. Infliximab has been proven to be highly effective in paediatric CD patients [2], but its primary use is reserved for patients with perianal disease or a predicted severe disease course [3]. We investigated whether starting top-down infliximab immediately after diagnosis is more effective than conventional step-up treatment in achieving and sustaining remission in children with moderate to severe CD.
Reduced need for surgery and medical therapy after early ileocaecal resection for Crohn’s Disease: Long-term follow-up of the LIR!C trial
The LIR!C trial was a randomised controlled trial conducted between 2008 and 2015. It included 143 patients with non-stricturing ileocaecal Crohn’s Disease (<40 cm) who failed conventional treatment.
Similarities and differences in the pathogenesis of immune-mediated inflammatory disorders
This year’s SciCom Workshop focussed on common and distinct pathways in immune-mediated disorders and the application of this knowledge for early disease recognition and interception as well as for the treatment of established disease.
During the ECCO’20 Vienna Congress, the Scientific Committee cordially welcomed Konstantinos Papamichail and Yves Panis as new members of SciCom.
Konstantinos Papamichail has been an ECCO Member since 2007 and has participated in several ECCO Activities, including the 7th ECCO Advanced Course and the ECCO ‘EXIT strategies’ Topical Review. He is a reviewer of the ECCO Grants and also a member of the editorial board of JCC. After completing his PhD in Pharmacology and his GI Fellowship in Greece, Kostas joined the Leuven IBD group as a post-doctoral researcher for 3 years and was also a recipient of an ECCO Fellowship. For the last 5 years he has been working at the Beth Israel Deaconess Medical Center in Boston, where his research has focussed on the role of therapeutic drug monitoring of biologics in IBD. He is the author of numerous publications and his goal is to stimulate scientific interactions in the ECCO Community and beyond and to interact with the other ECCO Committees in order to promote and support national and international IBD research efforts towards the better care of patients with IBD.
Laurent Peyrin-Biroulet is Professor of Gastroenterology and head of the Inflammatory Bowel Disease (IBD) group at the Gastroenterology Department, University Hospital of Nancy, France. He is also the current President of the Groupe d'Etude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID). As of February 15, he has been the new President of ECCO and we interviewed him during the ECCO Congress in Vienna.
Addition of azathioprine to the switch of anti-TNF in patients with IBD in clinical relapse with undetectable anti-TNF trough levels and antidrug antibodies: a prospective randomised trial
Roblin X, Williet N, Boschetti G, Phelip JM, Del Tedesco E, Berger AE, Vedrines P, Duru G, Peyrin-Biroulet L, Nancey S, Flourie B, Paul S.
Gut. 2020 Jan 24. doi: 10.1136/gutjnl-2019-319758. [Epub ahead of print]
Anti-tumour necrosis factor-α (anti-TNF) has historically been the mainstay of biologic therapy in Inflammatory Bowel Disease (IBD). However, of those who initially respond to anti-TNF, almost 50% will suffer secondary loss of response (SLR) over subsequent years [1,2]. This SLR is primarily predicated on suboptimal anti-TNF trough levels, with or without detectable anti-drug antibodies (ADAs) [3]. Furthermore the prospective, observational study by Kennedy et al. demonstrated that suboptimal anti-TNF trough levels at week 14 predicted ADAs, low trough levels and worse clinical outcomes [4]. This risk was mitigated for both infliximab and adalimumab by the use of immunomodulators such as azathioprine. This corroborates the retrospective data from other cohorts showing how the addition of an immunomodulator can restore clinical response and favourable pharmacokinetics [5–7]. Remission rates when switching to a second anti-TNF have been shown to be lower when the reason to withdraw the first anti-TNF is SLR as compared to intolerance (45% vs 61%) [8]. In the event that SLR to anti-TNF is due to immunogenicity, a switch to another anti-TNF is associated with a risk of ADA to this new therapy [9,10]. A number of patients will also be on anti-TNF monotherapy at the time of switching having de-escalated from previous combination therapy. We know that open-ended prescription of anti-TNF with azathioprine is not without additional risk, notably infection and lymphoma [11]. Furthermore, de-escalation to anti-TNF monotherapy after a period of combination therapy has been shown in most studies not to impact on relapse rates (49% monotherapy versus 48% combination therapy) [12]. It is in precisely this important group of patients that Roblin et al. sought to compare the use of azathioprine in combination with a second anti-TNF versus this second anti-TNF as monotherapy. Over a follow-up period of 2 years, the rates of clinical and immunogenic failure, and of adverse events, were compared.
Proactive monitoring of adalimumab trough concentration associated with increased clinical remission in children with Crohn's Disease compared with reactive monitoring
Assa A, Matar M, Turner D, Broide E, Weiss B, Ledder O, Guz-Mark A, Rinawi F, Cohen S, Topf-Olivestone C, Shaoul R, Yerushalmi B, Shamir R
Therapeutic drug monitoring (TDM) of the anti-TNF monoclonal antibodies, infliximab and adalimumab, in patients with Inflammatory Bowel Disease is gradually being adopted into routine clinical practice in the United Kingdom [1] and United States [2]. The aim of TDM, measuring an individual’s drug and anti-drug antibody levels, is to assess compliance, drug metabolism and immunogenicity with a view to guiding adjustments or changes in management in order to improve clinical outcomes1. TDM can be proactive, with routine measurement of drug level and anti-drug antibody regardless of clinical outcome, or reactive, with measurement of drug level and anti-drug antibody in the setting of loss of response [3]. Compared to empirical dosing alone, TDM used reactively, at the time of loss of response to an anti-TNF treatment, improves durability of response and safety and leads to significant cost savings [4,5]. The evidence base supporting proactive over reactive TDM is, however, less clear. Two randomised controlled trials done in adults (TAXIT [6] and TAILORIX [7]) did not demonstrate any differences in biological, endoscopic or corticosteroid-free remission between groups, though these trials were limited by methodological limitations and isolating the effect of proactive TDM on defined outcomes was difficult. In contrast, multiple observational studies have concluded that there is less risk of treatment failure and relapse, higher rates of drug persistence and better clinical outcomes in patients who undergo proactive TDM compared to reactive TDM [8–11]. The authors aimed to add to this debate by carrying out a pragmatic, randomised controlled trial assessing whether proactive TDM is superior to reactive testing in children with Crohn’s Disease.
Vedolizumab versus adalimumab for moderate-to-severe Ulcerative Colitis
Sands BE, Peyrin‑Biroulet L, Loftus E, Danese S, Colombel JF, Toruner M, Jonaitis L, Abhyankar B, Chen J, Rogers R, Lirio RA, Bornstein JD, Schreiber S, for the VARSITY Study Group
N Engl J Med 2019;381:1215–26. doi: 10.1056/NEJMoa1905725
The management of Ulcerative Colitis (UC) increasingly involves the use of a biologic agent. Placebo-controlled trials have demonstrated the efficacy of both adalimumab, a tumour necrosis factor (TNF) inhibitor, and vedolizumab, an integrin inhibitor. However, variation in study design makes comparison between such trials difficult. This is particularly evident when comparing rates of clinical remission in the placebo groups of different trials. For example, in the ULTRA 2 trial, which established the superiority of adalimumab over placebo in moderate to severe UC, the 52-week clinical remission rate in the placebo group was just 8.5% compared to 15.9% in GEMINI 1, the placebo-controlled trial of vedolizumab [1,2]. In the absence of head-to-head trials between biologics there is a lack of data to inform clinicians of the best choice of agent. VARSITY is the first head-to-head trial to compare the efficacy and safety of vedolizumab and adalimumab in moderate to severely active UC.
Tim Raine 
Michael Scharl
Sebastian Zeissig
Charlotte Hedin 
