Crohn’s disease (CD) and ulcerative colitis (UC), known as inflammatory bowel diseases (IBD), are characterized by chronic inflammation of the gastrointestinal tract. Over the last two decades, numerous medications have been developed and repurposed to induce and maintain remission in IBD patients. Despite the approval of multiple drugs, the major recurring issues continue to be primary non-response and secondary loss of response, as well as short- and long-term adverse events. Most clinical trials show percentages of response under 60%, possibly as a consequence of strict inclusion criteria and definitions of response. That is why these percentages appear to be more optimistic in real-life studies. A therapeutic ceiling has been used as a term to define this invisible bar that has not been crossed by any drug yet. This review highlights novel therapeutic target agents in phases II and III of development, such as sphingosine-1-phosphate receptor modulators, selective Janus kinase inhibitors, anti-interleukins, and other small molecules that are currently under research until 1 January 2023. Emerging treatments for CD and UC that have just received approval or are undergoing phase III clinical trials are also discussed in this review.

The pathogenesis of inflammatory bowel disease (IBD) involves a complex interplay between genetic, environmental, and microbial factors. Many of these environmental determinants are modifiable, offering opportunities to prevent disease or delay its onset. Advances in the study of preclinical IBD cohorts offer the potential to identify biomarkers that predict individuals at high risk of developing IBD, enabling targeted environmental interventions aimed at reducing IBD incidence. This review summarizes findings from 79 meta-analyses on modifiable environmental factors associated with the development of IBD. Identified risk factors include smoking, Western diets, ultra-processed foods, and early life antibiotic use, while protective factors include breastfeeding, Mediterranean diets rich in fiber, plant-based foods, and fish, along with an active physical lifestyle. Despite the promise shown by observational data, interventional or randomized controlled studies evaluating the efficacy of modifying environmental risk factors remain limited and mostly focus on dietary intervention. This review aims to inform the design of higher quality interventional and randomized controlled studies for disease prevention while providing actionable guidance to healthcare providers on reducing the risk of developing IBD through environmental modifications.

Background: Filgotinib is a small molecule with preferential inhibition of Janus kinase type 1, approved for the treatment of ulcerative colitis in Scotland in May 2022. We present the first real-world experience on its use in clinical practice. Methods: In this retrospective, observational, cohort study we assessed patients with active ulcerative colitis who received filgotinib in NHS Lothian, Scotland. Baseline demographic, phenotype, and follow-up data were collected via review of electronic medical records. Results: We included 91 patients with median treatment duration of 39 weeks (interquartile range [IQR] 23-49). Among the cohort, 67% [61/91] were biologic- and small molecule-naïve, and 20.9% [19/91] had failed one and 12.1% [11/91] two or more classes of advanced therapy. Of the biologic- and small molecule-naïve patients, 18% [11/61] were also thiopurine-naïve. Clinical remission [partial Mayo score <2] was achieved in 71.9% [41/57] and 76.4% [42/55] of patients at Weeks 12 and 24 respectively. Biochemical remission [C reactive protein ≤5 mg/L] was achieved in 87.3% [62/71] at Week 12 and 88.9% [40/45] at Week 24. Faecal biomarker [calprotectin <250 µg/g] remission was achieved in 82.8% [48/58] at Week 12 and 79.5% [35/44] at Week 24. At the end of follow-up, median 42 weeks [IQR 27-50], 82.4% [75/91] of patients remained on filgotinib. Severe adverse events leading to drug discontinuation occurred in 2.2% [2/91] and there were 8.8% [8/91] moderate adverse events that required temporary discontinuation. Conclusion: These are the first reported data on the real-world efficacy and safety of filgotinib in ulcerative colitis. Our findings demonstrate that filgotinib is an effective and low-risk treatment option for these patients.

Background: Switching from originator infliximab (IFX) to biosimilar IFX is effective and safe. However, data on multiple switching are scarce. The Edinburgh inflammatory bowel disease (IBD) unit has undertaken three switch programmes: (1) Remicade to CT‐P13 (2016), (2) CT‐P13 to SB2 (2020), and (3) SB2 to CT‐P13 (2021).Objective: The primary endpoint of this study was to assess CT‐P13 persistence following switch from SB2. Secondary endpoints included persistence stratified by the number of biosimilar switches (single, double and triple), effectiveness and safety.Methods: We performed a prospective, observational, cohort study. All adult IBD patients on IFX biosimilar SB2 underwent an elective switch to CT‐P13. Patients were reviewed in a virtual biologic clinic with protocol driven collection of clinical disease activity, C‐reactive protein (CRP), faecal calprotectin (FC), IFX trough/antibody levels, and drug survival.Results: 297 patients (CD n = 196 [66%], ulcerative colitis/inflammatory bowel disease unclassified n = 101, [34%]) were switched (followed‐up: 7.5 months [6.8–8.1]). This was the third, second and first IFX switch for 67/297 (22.5%), 138/297 (46.5%) and 92/297 (31%) of the cohort respectively. 90.6% of patients remained on IFX during follow‐up. The number of switches was not independently associated with IFX persistence after adjusting for confounders. Clinical (p = 0.77), biochemical (CRP ≤5 mg/ml; p = 0.75) and faecal biomarker (FC<250 µg/g; p = 0.63) remission were comparable at baseline, week 12 and week 24.Conclusion: Multiple successive switches from IFX originator to biosimilars are effective and safe in patients with IBD, irrespective of the number of IFX switches.

Inflammatory bowel disease (IBD) management stands at the cusp of a transformative era, with recent breakthroughs heralding a paradigm shift in treatment strategies. Traditionally, IBD therapeutics revolved around immunosuppressants, but the landscape has evolved significantly. Recent approvals of etrasimod, upadacitinib, mirikizumab, and risankizumab have introduced novel mechanisms of action, offering renewed hope for IBD patients. These medications represent a departure from the status quo, breaking years of therapeutic stagnation. Precision medicine, involving Artificial Intelligence, is a pivotal aspect of this evolution, tailoring treatments based on genetic profiles, disease characteristics, and individual responses. This approach optimizes treatment efficacy, and paves the way for personalized care. Yet, the rising cost of IBD therapies, notably biologics, poses challenges, impacting healthcare budgets and patient access. Ongoing research strives to assess cost-effectiveness, guiding policy decisions to ensure equitable access to advanced treatments. Looking ahead, the future of IBD management holds great promise. Emerging therapies, precision medicine, and ongoing research into novel targets promise to reshape the IBD treatment landscape. As these advances continue to unfold, IBD patients can anticipate a brighter future, one marked by more effective, personalized, and accessible treatments.