Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the Immunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study
Anti-TNF monoclonal antibodies play an important role in the management of immune-mediated inflammatory diseases, including Inflammatory Bowel Disease [1]. However, anti-TNF failure is common [2]. Loss of response is usually associated with the development of anti-drug antibodies and low anti-TNF drug levels.
The aim of this study was to evaluate the relationship between immunogenicity to a patient’s first anti-TNF therapy and immunogenicity and drug persistence to the second anti-TNF therapy, irrespective of drug sequence.
I hope you are all well and into the winter workflow. Many of us were representing IBD at the UEGW earlier in October, and many will have taken advantage of the excellent postgraduate course. Here in the ECCO Community we are excited soon to be launching The IBD Communication Toolbox. This is a series of podcasts where you can hear how IBD experts deal with questions that are commonly asked by patients. Firstly, the questions and topics addressed in the Communication Toolbox were selected in collaboration with patient representatives, ensuring that these are topics with high relevance for the IBD patients you meet in your practice.
ECCO is an ever-expanding organisation with educational activities which extend throughout the year. For this ECCO News I spoke with Nicole Eichinger, the Executive Director of ECCO, to find out a bit more about her and how the ECCO Team work behind the scenes to keep this vital organisation running as smoothly as it does.
In the United Kingdom (UK), approximately 500,000 people live with IBD, and in the coming decade it is anticipated that the prevalence of IBD will surpass 1% of the population [1]. In 2019, the third UK IBD Standards for adults and children were published following extensive patient and healthcare professional consultation [2]. The IBD Standards cover seven domains: service design and delivery; pre-diagnosis referral pathways; management of the newly diagnosed patient; flare management, including self-management and timely access to specialist advice; surgery including pre- and postoperative care; inpatient medical care; and ongoing long-term treatment and monitoring in both secondary and primary care.
Inflammatory Bowel Disease (IBD) is a long-term condition of the gut which is known to impact the quality of life and social functioning of those affected due to the chronic nature of symptoms. These factors, along with communication across the gut–brain axis, cause many patients to suffer from mental health disorders such as anxiety and depression [1]. Previously, the magnitude of these comorbidities had not been established, but recent studies [1, 2] have found the prevalence to be high: a third of all patients and a half of those with an active IBD flare have been found to suffer from anxiety, while depression has been found to affect a quarter of patients and a third of those with active symptoms.
Furthermore, compared with controls, patients with IBD and mental health disorders show increased use of healthcare resources (both primary care visits and emergency secondary care visits) and increased use of antidepressant and anxiolytic medications [2]. While antidepressant medications are commonly used to treat anxiety and depression in IBD [3], understanding of how effectively these treatments are prescribed remains limited, and this is particularly true regarding the adequacy of duration of treatment in this cohort.
This population-based study was performed in the United Kingdom and used data from the primary care setting that was routinely collected electronically in general practices as part of the Clinical Practice Research Datalink (CPRD). The authors looked to review the antidepressant prescribing in primary care for those diagnosed with IBD. They focused on the rate of antidepressant treatment initiation following IBD diagnosis, the duration of antidepressant treatment according to international guidelines, potential risks of inadequate antidepressant treatment duration and general trends in antidepressant prescribing.
Many clinicians have anecdotally observed patients opting out of colonoscopies due to unpleasantness related to the procedure, and within Inflammatory Bowel Disease (IBD) populations a number of factors have been implicated in non-adherence, including logistics, health perceptions, stress and procedure problems (including discomfort) [1].
Prior studies have demonstrated patient preferences for propofol sedation over midazolam and fentanyl sedation for outpatient colonoscopy in general [2]. Furthermore, propofol has been shown to be safe, without severe adverse events or accidents [3], and nurse-administered propofol has specifically proven to be an efficient means of sedation for endoscopy in low-risk patients [4]. Nevertheless, this area has yet to be explored in the specific cohort of IBD patients.
Modern management of IBD requires the employment of ileocolonoscopy for diagnosis, as well as for the surveillance and guidance of future management. The investigators here looked to fill the aforementioned knowledge gap through design of a trial investigating the effectiveness of deep nurse-administered propofol sedation (NAPS), versus moderate midazolam and fentanyl sedation, as a means of improving patient satisfaction and future attitude towards colonoscopies.
For very well-known pandemic reasons, we twice had to postpone the first Y-ECCO Mentorship Forum. Our third appointment with ECCO History proved to be the right one: in June 2022 we finally succeeded in completing our first Y-ECCO Mentorship Forum. Thanks to very active Y-ECCO participants and a stellar ECCO Faculty (Ailsa Hart, Peter Irving, Charlie Lees, Janneke Van der Woude and Johan Burisch), this networking and educational event was a great success. .
I hope you have all had time to re-charge over the summer! ECCO'23 abstract submission is currently open, with a deadline of November 21. Basic science abstracts can be considered for an Oral Presentation during the 9th Y-ECCO Basic Science Workshop, which will be held on Wednesday, March 1, 2023, between 13:05 and 15:30 CET – please tick the box if you are a Y-ECCO Member and would like to be part of this great interactive session.
Y-ECCO Interview Corner gives us the opportunity to gain insights into members of the IBD Community, what they do and how they got to where they are. For this edition, I caught up with Dr. Karen Edelblum , a scientist who has a unique and important perspective.
Karen Edelblum combines cell biology and mucosal immunology, with some stunning time-lapse microscopy. She aims to understand how we might harness immune–epithelial interactions in the treatment of Inflammatory Bowel Disease. Having trained at Vanderbilt University and the University of Chicago, she is now assistant professor at Rutgers New Jersey Medical School. We met (over an internet connection) to get her insights into IBD and the science that will move it on.
Traditionally, treatment of Crohn’s Disease (CD) has focused on symptomatic, clinical and corticosteroid-free remission. However, more recent studies have shown that endoscopic remission is associated with more favourable patient long-term outcomes [1, 2]. It has been hypothesised that more intense treatment regimens may increase the likelihood of endoscopic remission in CD patients. Previous studies (such as that performed by the DIAMOND study group) have indicated that adalimumab trough levels are higher in CD patients who achieve an endoscopic response and mucosal healing at weeks 26 and 52 [3]. Further to that, the personalised anti-TNF therapy in Crohn's Disease study (PANTS) demonstrated that low drug levels were predictive of anti-tumour necrosis factor (anti-TNF) treatment failure [4].
Various methods of dose optimisation have been postulated, such as higher induction doses, therapeutic drug monitoring (TDM) to guide dose optimisation during the maintenance phase or a clinically adjusted (CA) dose optimisation strategy.
Robin Dart
Bram Verstockt
Robin Dart