Two new drugs have recently been approved by the European Medical Agency and one additional strategy will soon follow. With regard to the first part, this includes Filgotinib, an addition to the Janus Kinase inhibitor class with a higher specificity to Jak1. Furthermore, an entire new class has entered the field of IBD by the introduction of Ozanimod the first S1P receptor modulator. Last, anti-IL-23 antibodies are expected to be approved soon. The data of the clinical studies will be shortly summarized and all three drugs will be placed in our current treatment algorithm by discussing efficacy, side-effects as well as the role with regard to extraintestinal manifestations.

Educational Objectives:
1. To understand the mode of action of the three drugs described
2. To review the clinical trials that resulted in the approval of these drugs.
3. To know potential side-effects and required strategies.
4. Identify a possible role within the treatment algorithm.

An overview of the use of 5-ASA, steroids and immunomodulators in IBD 

- Role and efficacy of Fecal microbiota transplantation in IBD
- Role and efficacy of new nutritional intervention in IBD

Alteration in body composition are common in IBD patients and are often not recognized. Rates of obesity in IBD patients are rising over time, driven by gains in fat mass, while lean mass decreases. As (sarcopenic) obesity can independently predict poor disease outcomes during IBD course, the impact of body composition on the IBD disease course will be studied. In this presentation, we will try to unravel whether obesity can lead to the development of IBD and whether IBD can contribute to obesity.

Current literature predominantly uses BMI as a marker of nutritional status. Since augmentation of body composition parameters in the clinical setting could improve IBD outcomes, it is important that clinicians recognize that an increase in BMI may obscure a decrease in muscle mass. This presentation will finish with some practical treatment advices on body composition in IBD patients such as measurement of bio-impedance or hand grip strength alongside with BMI to predict lean muscle mass.

Educational Objectives:
1. To recognize the prevalence of (sarcopenic) obesity in IBD
2. To review the impact of obesity on the development of IBD
3. To understand the impact of obesity on disease course
4. To have an overview of practical measurement tools to reveal body composition in IBD patients

Educational objectives:
1. To understand the role of 5-ASA in the treatment of IBD and the most frequent mistakes made in 5-ASA treatment
2. To review the evidence for dosing and treatment routes for the different localizations of inflammation in UC and CD
3. To emphasise the role of rectal 5-ASA therapy in proctitis and left sided colitis and the important role of oral/rectal combination therapy
4. To have an overview over optimal treatment strategies with 5-ASA

Inflammatory bowel disease (IBD) are chronic diseases affecting different segments of the digestive tract, also associated with extra-intestinal sites of inflammation. Global research has more intensively focused in developing novel pharmaceutical agents the last 30 years, due to a gradual increase in incidence and prevalence of IBD. 5-aminosalicylic acid (5-ASA) represent one of the older drug classes used for the treatment of IBD patients. The exact mechanism of action has not been elucidated. Proposed mechanisms are: (A) modulation of the inflammatory response originating from the cyclooxygenase and lipooxygenase pathways leading to a decrease of the synthesis of prostaglandins and leukotrienes, (B) interference with the production of inflammatory cytokines via decreasing the activity of nuclear factor­ κB, and inhibiting tumor necrosis factor and (C) interference with cellular functions of mucosal lymphocytes, macrophages, and natural killer cells. Properties of free radical scavengers and antioxidants have also been postulated. 5-ASA are recommended for the induction and maintenance of remission in mild-to-moderately active ulcerative colitis but are also used in cases with mild Crohn’s disease, although this practice is rather originating from uncontrolled observational data or expert opinion-based and not a formal recommendation in most of the major national or international guidelines. Oral and rectal formulation of 5-ASA exist and the choice of the most appropriate regimen depends on disease extent, localization and severity, the sites of the digestive tract that each formulation is released and patient’s preference. In general, a combination of both formulations is considered the most potent treatment. Safety profile is acceptable with the vast majority of the adverse events being reversible. Monitoring includes principally renal and hepatic function and complete blood count. 5-ASA are relatively fast acting drugs for symptom relief. However, remission may need up to 4-6 weeks to establish. Thus, timely design of optimal treatment strategies with 5-ASA is of utmost importance.  

CT-P13 is the first and only subcutaneous (SC) formulation of infliximab (IFX) which received EMA approval in July 2020 for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC). This study compares efficacy and safety between IFX SC and vedolizumab (VDZ) in moderate-to-severe CD or UC patients using data from the pivotal study of IFX SC, VISIBLE 2 and recently presented systematic literature review and meta-analysis [1].

This comparative study analyses 7 randomised controlled trials. The IFX SC trial (NCT02883452) was compared with the VDZ trials including GEMINI II, GEMINI III, VISIBLE 2 for CD and GEMINI I, VISIBLE 1, and VARSITY for UC. VISIBLE 2 was added in this analysis as it was published after the presented meta-analysis. In all studied VDZ trials, only responders at week 6 continued to receive maintenance treatment except VARSITY trial, which followed a treat-through design.

In the patients with CD, IFX yielded significantly better efficacy results in the induction phase compared to VDZ with non-overlapping 95% confidential interval while IFX SC displayed better results, although statistically non-significant during the maintenance phase (Table 1). In UC, similar efficacy was shown between the treatments during both induction and maintenance phase (Table 2). The proportion of patients discontinued due to lack of efficacy was significantly higher in VDZ compared to IFX SC in both CD (IFX SC 5% and VDZ 32%) and UC (IFX SC 3% and VDZ 15%) over 1 year (Tables 1,2).

The safety profiles were generally comparable between IFX SC and VDZ. Similar proportion of patients experienced serious adverse event (9% and 14% in CD; 12% and 11% in UC in IFX SC and VDZ). The proportion of patients experiencing serious infection between the treatments was also similar in both CD and UC (Tables 3,4).

Better efficacy was shown in IFX SC compared to VDZ in CD, while a similar efficacy was shown in UC. A significantly higher proportion of patients were discontinued due to lack of efficacy in VDZ compared to that of IFX SC over 1 year. Safety profiles over 1 year were generally comparable between IFX SC and VDZ in both indications.

Reference
[1] Peyrin-Biroulet, L. (2021). P0414 Efficacy and safety of infliximab and vedolizumab in patients with inflammatory bowel diseases: a systematic review and meta-analysis. Poster presented at: 2021 UEG Week.