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.
Bringing basic science from the bench to the bed, and back, can be challenging for both scientists and clinicians. In order to encourage young scientists and clinicians to collaborate and to approach similar scientific questions from a different – but joint – perspective, the Y-ECCO Basic Science Workshop was founded years ago. Every year, the Y-ECCO Committee invites outstanding senior experts to give a state of the art overview on hot topics in the field. Furthermore, these top-notch speakers not only moderate the discussions following abstract presentations but also inspire and stimulate full-time researchers and young clinicians to do basic science at the start of their careers.
The 9th S-ECCO Masterclass (held in collaboration with the European Association of Coloproctology, ESCP) was organised during the 15th Congress of ECCO in Vienna. Thankfully, just before the coronavirus crisis!
As in previous years, it was a full-day masterclass, and once again it attracted a large number of participants, 149. This meant that in terms of attendance the S-ECCO Masterclass was second among all masterclasses and symposia, just after the N-ECCO Network Meeting.
D-ECCO, the Dietitians of ECCO, held its 5th Workshop as part of the 15th ECCO Congress in Vienna in February 2020. I will describe some of the highlights and main messages of the Workshop, which was attended by 104 registered delegates.
On the evening of Wednesday, February 12, 16 nurses from 11 countries across Europe participated in our yearly N-ECCO National Representatives Meeting.
As the N-ECCO Committee Member responsible for the National Representatives, I welcomed the attendees, and this was followed by a short round of introductions. An exchange of nurses every 2–3 years is greatly encouraged by N-ECCO, but many countries nevertheless retain the same National Representatives for more than 3 years. New people tend to mean new ideas, although some countries have different service setups and getting new representatives is sometimes difficult.
The 14th N-ECCO Network Meeting was opened by Susanna Jäghult(Sweden), N-ECCO Chair. In total, 255nurses from across the world attended the meeting.
The first session focussed on presentations regarding “The IBD Nurse Education Programme”, which was performed and completed in Italy during 2018–2019. Palle Bager (Denmark) and Karen Kemp(United Kingdom) reported on the development of the programme and how it was conducted in Italy. Then, Simona Radice and Gionata Fiorino, both from Italy, described the country perspective on the programme. This aroused great interest among the audience and the second cycle is now in the pipeline.
The 11th N-ECCO School in Vienna was attended by 74 participants from 25 countries, including dietitians and IBD Nurses. The School covered various IBD topics of interest to both nurses and dietitians who work with IBD patients. The aim was to enhance participants’ basic knowledge in IBD, enabling them to provide better support to IBD patients throughout Europe and beyond. The N-ECCO School has also come to serve as a great networking opportunity, allowing nurses and dietitians to share their experiences.
The 6th N-ECCO Research Forum was attended by 52 nurses active and/or interested in research. The Research Forum is arranged every second year and this year was opened by Wladzia Czuber-Dochan (United Kingdom), who also presented the winners of the N-ECCO Research Grant 2020: Simona Fourie (UK) and Katarina Pihl Lesnovska (Sweden).
Bram Verstockt
Yves Panis 
Eytan Wine
Ana Ibarra 
Miriam Ganon
Wladzia Czuber-Dochan