Ulcerative Colitis: Are We on the Verge of a Treatment Revolution? For years, those battling ulcerative colitis (UC) have faced limited options and frustrating outcomes. But hold on – groundbreaking research presented at the 2025 United European Gastroenterology (UEG) Week in Berlin suggests we might be on the cusp of a new era in UC management. From surprising surgical approaches to updated guidelines for children and powerful drug combinations, the landscape is shifting dramatically. Let's dive into the key takeaways from this pivotal conference, originally reported by Helena Bradbury, EMJ, London, UK, and published in EMJ Gastroenterol. 2025;14[1]:24-27. https://doi.org/10.33590/emjgastroenterol/WSCL3189.
Appendectomy: A Cure for UC? Sounds Crazy, Right? Eva Visser from Amsterdam University Medical Center, the Netherlands, kicked things off with a truly provocative idea: could removing the appendix actually treat ulcerative colitis? It sounds wild, but the connection between the appendix and UC has been brewing since a 1987 study noticed lower appendectomy rates in UC patients compared to healthy individuals. The question is why? Visser proposes some intriguing theories. The appendix might act as a safe haven for beneficial gut bacteria, helping to repopulate the colon after disturbances. Or perhaps its lymphoid tissue plays a crucial role in the immune system, and when this system goes haywire, the appendix becomes a hotbed for UC development.
But here's where it gets controversial... Visser then asked the million-dollar question: "Can an appendectomy actually alter the disease course in ulcerative colitis?" Enter the ACCURE trial, an international randomized controlled trial (RCT). Patients with UC in remission were randomly assigned to either undergo a laparoscopic appendectomy plus standard therapy, or just receive standard therapy alone. The results? Astonishing. The appendectomy group showed significantly better remission rates at one year: 36.4% relapse rate in the appendectomy arm versus a whopping 56.1% in the control arm.
Building on this intriguing link, researchers wondered if the appendectomy advantage extended to patients with active UC. The PASSION trial, an observational study, examined patients with therapy-resistant UC slated for proctocolectomy (removal of the colon and rectum). These patients were offered a laparoscopic appendectomy beforehand. After 12 months, a surprising 30% experienced lasting clinical response, with 17% achieving endoscopic remission.
Finally, Visser presented COSTA (Visser E et al., unpublished data), the first controlled, multi-center, patient-preference, international cohort trial. This study involved 116 patients with active UC who had previously failed biologic therapies. The goal? To compare the effectiveness of laparoscopic appendectomy versus JAK inhibitor therapy in inducing remission. The results were compelling: 32.8% of patients in the appendectomy group achieved remission at 12 months without therapy failure, compared to just 12.2% in the JAK inhibitor group. This suggests that appendectomy could be a feasible, well-tolerated, and effective option for patients with difficult-to-treat, biologic-exposed UC.
Paediatric Ulcerative Colitis: Updated Guidelines for Our Youngest Patients: Patrick van Rheenen, University Medical Center Groningen, the Netherlands, shifted the focus to the specific challenges of managing UC in children. He stressed the importance of IBD specialists having deep knowledge of paediatric UC, as kids often experience more widespread disease. This understanding is crucial for guiding treatment pathways before they transition to adult care. And this is the part most people miss... the treatment options approved for children are severely limited compared to adults (infliximab, adalimumab, vedolizumab, ustekinumab, and tofacitinib). The approval process can be painfully slow (infliximab took 6 years, adalimumab 9 years!), leaving doctors with fewer tools to help their young patients.
Van Rheenen then outlined the rigorous methodology used to develop the 2025 clinical guidelines3,4, including PICO frameworks, standardized literature searches, online voting rounds, and a face-to-face consensus meeting. The goal was to ensure accuracy and comprehensiveness.
So, what's new since the 2016 guidelines? While treatment for mild-to-moderate UC remains largely unchanged, the updated guidelines address the management of severe disease and those needing more than conventional therapy. Key changes include higher infliximab dosing for both ambulatory and acute severe colitis, the importance of therapeutic drug monitoring with anti-TNFs, the use of other advanced therapies, the emerging role of intestinal ultrasounds, and the sequencing of new treatments in advanced severe UC.
A major point was higher infliximab dosing and proactive therapeutic drug monitoring. For ambulatory UC, the guideline recommends 10 mg/dose at Weeks 0, 2, and 6, followed by 10 mg/kg every 4–8 weeks for maintenance. Therapeutic drug monitoring aims to maintain the lowest drug concentration in the bloodstream needed for the best outcome. For example, in uncomplicated UC, the target through is ≥25 mg/kg at Week 2, ≥15 mg/kg at Week 6, and 8–10 mg/kg at Week 14. The guidelines now recommend monitoring these levels at Week 14 to ensure they stay within the target range.
Van Rheenen then detailed the recommended treatment sequence for paediatric acute severe UC. Day 1 (PUCAI score ≥65): methylprednisone. Day 3 (PUCAI score ≥45): transfer to a referral paediatric IBD centre. Day 5 (PUCAI score ≥65): begin second-line treatment (infliximab, cyclosporin, or tacrolimus). Infliximab is the preferred second-line rescue therapy: 10 mg/kg/dose at Weeks 0, 1, and 3, followed by 10 mg/kg every 2–4 weeks. Tacrolimus or cyclosporin are alternatives, especially if infliximab fails.
Finally, van Rheenen discussed the extrapolation strategy: if a drug is approved for adolescents (>12 years; >40 kg), it should also be considered for children (2–12 years; <40 kg), given the similar pharmacokinetics.
Combining Therapies in Ulcerative Colitis: A Powerhouse Approach? Joana Torres, Hospital Beatriz Ângelo, Loures, Portugal, tackled the idea of combining different treatment strategies for UC. Despite the growing number of available therapies, she pointed out that efficacy rates have stalled, with fewer than 50% of patients achieving clinical remission after a year.
Torres argued for combination therapies, explaining that monotherapy often falls short and that targeting multiple pathways increases the odds of success. She also noted that biologics tend to lose effectiveness over time, and that starting combination therapy early might prevent the development of anti-drug antibodies or escape mechanisms, thus prolonging the response.
The key question is: which therapies should we combine? Torres focused on advanced combination therapies: two targeted agents (either two biologics or a biologic plus a small molecule). She emphasized selecting therapies with complementary, non-overlapping mechanisms of action, while prioritizing safety.
But it's not just what you combine, but when and how you administer them, along with careful patient monitoring. During induction therapy, you can use an add-on, simultaneous, or sequential approach. For maintenance, you might withdraw the first biologic, continue both, or maintain one biologic with short courses of the second.
Torres highlighted that, unlike in cancers, advanced combination therapy in UC is still largely experimental. She mentioned the VEGA trial6, a Phase II trial that showed guselkumab plus golimumab combination therapy was more effective than golimumab monotherapy (83% clinical response versus 61%).
Torres concluded by advocating for early induction of advanced combination therapies to prevent therapeutic resistance, but cautioned that this should be done in specialized centres with the resources for close patient monitoring. She also highlighted the potential of bi-specific antibodies and nanobodies, which can target two pathways simultaneously, and innovative clinical trial designs like platform trials.
Conclusion: A New Dawn for UC Treatment? This session underscored the rapid evolution of UC treatment, with innovations in surgery, paediatric management, and combination therapies. These advances point towards a more personalized, multidisciplinary approach to improving long-term outcomes for UC patients.
Now, it's your turn! What do you think about the potential of appendectomy as a UC treatment? Are you excited about the updated paediatric guidelines? And how do you feel about the idea of combining powerful therapies? Share your thoughts and experiences in the comments below! Let's discuss these exciting developments and help each other navigate the ever-changing world of UC treatment.
