Implementing modern therapeutic goals for chronic inflammatory bowel diseases in practice to improve the long-term outcome of patients

22.10.2025 16:25

Disease Clearance – zusammengesetzt aus den Endpunkten klinische, endoskopische und histologische Remission – ist ein neues anzustrebendes Therapieziel bei Colitis ulcerosa (CU). [1] Interimsdaten der VERDICT-Studie zeigen, dass mit Vedolizumab (Entyvio®[a]) eine Disease Clearance bei CU erreicht werden kann. [2] Es gibt erste Hinweise, dass eine transmurale Heilung bei Morbus Crohn (MC) als ambitioniertes Therapieziel mit Vedolizumab erreichbar ist – so Daten der Post-hoc-Analyse der VERSIFY-Studie. [3]

„"Nothing in IBD management should be torture!" was the impassioned plea from Prof. Dr. Irina Blumenstein, Frankfurt am Main, at the beginning of the Takeda-supported symposium on the occasion of Visceral Medicine 2025 of the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS). The gastroenterologist continued: "We care for our patients in absolute crisis situations. With the right therapy, we can ensure that the tide turns and their quality of life returns to normal—and that should always be our overriding therapeutic goal!"“

When reviewing the current treatment situation for the two chronic inflammatory bowel diseases (IBD) UC and MC, Blumenstein called for a more timely and accurate diagnosis in adult patients. Furthermore, the most appropriate treatment goal for each individual – in addition to normalizing quality of life – should be defined together with those affected, from which they can benefit most in the long term. It is also important to review whether the goal has been achieved or not – and to take appropriate action if necessary.

Choice of therapy goal and treatment option – IBD management is always individual

The current STRIDE II recommendations (Selecting Therapeutic Targets in Inflammatory Bowel Disease) suggest, among other things, rapid symptom control with effective anti-inflammatory effects and long-term endoscopic remission as treatment goals for UC and MC. [4] In the future, transmural cure for MC or histological cure for UC could be recommended [4], Blumenstein explained. "In MC, there is increasing evidence that treatment as early as possible after diagnosis is advisable," Blumenstein continued. The PROFILE study clearly demonstrated this in favor of a top-down strategy. [5] The gastroenterologist's recommendation was that appropriate treatment should be started as quickly as possible, particularly in cases of risk factors for a more complicated course, such as multifocal involvement, hesitant or lacking response to steroids, active smoking and the presence of extraintestinal manifestations, or in cases of an existing desire to have children.

Today, a wide range of options are available for IBD treatment after conventional therapies have failed. "The guidelines do not prioritize individual drug recommendations, so we have the freedom to make individual treatment decisions in our daily practice," emphasized Blumenstein. Important factors for treatment choice include efficacy, prior treatments, safety, and long-term treatment control, as well as individual parameters such as age, disease pattern, comorbidities, and extraintestinal manifestations. However, patient preferences also play a key role in the selection process.

Disease clearance – an emerging concept in the treatment of ulcerative colitis

Prof. Dr. Timo Rath, Erlangen, explained that in UC, histologically detectable disease activity often still exists despite endoscopic remission. [8] Therefore, histological remission is given high priority. It has been shown that achieving endoscopic and histological remission is associated with a significantly lower risk of recurrence than purely clinical remission. [8] Therefore, "disease clearance" is a desirable therapeutic goal in UC, which consists of the combination of the three endpoints symptomatic, endoscopic, and histological remission. [1] "Disease clearance can be a first step towards changing the course of the disease. In my opinion, disease clearance can change the future for UC patients," Rath said. A post-hoc analysis of the VARSITY study clearly demonstrated that disease clearance is not an unrealistic dream for a number of UC patients, but a realistic therapeutic goal: 29.2% of patients achieved disease clearance [b] under vedolizumab, compared to 16.3% under adalimumab. [9]

VERDICT study – provides evidence for the new therapeutic target in ulcerative colitis

Further insights into disease clearance under vedolizumab will be provided by the VERDICT study [c], [10], which evaluates the optimal treatment goal in moderately to severely active UC and also looks at the achievement of disease clearance. In the study, participants were randomized into three groups with different treatment goals. For group 3, the endpoint was steroid-free disease clearance, i.e. steroid-free symptomatic remission (Mayo subscore for rectal bleeding = 0) plus endoscopic remission (endoscopic Mayo score ≤ 1) plus histological remission (Geboes score < 2B.0). [10] Treatment was escalated with vedolizumab (300 mg iv) according to a treatment algorithm that depended on the patient's baseline therapy until the goal was reached at week 16, 32, or 48. In patients who did not achieve their treatment goal due to lack of remission (with or without corticosteroid use), a dose escalation with vedolizumab to a maximum of 300 mg every 4 weeks was performed. [10] Rath presented the current data from an interim analysis: After 48 weeks of treatment, 67.2% (123/183) [d] of the participants in group 3 with evaluable remission status had achieved steroid-free disease clearance. [2] "This means that 2 out of 3 patients have achieved this treatment goal!"„

The rates among biologic-naive patients in group 3 were 70.1% (110/157)d and among biologic-experienced patients 50.0% (13/26)d. [2] Rath emphasized: "These initial VERDICT data have shown that by optimizing an existing therapy—for example, by shortening the interval—disease clearance can be achieved and thus the prognosis of the disease can be significantly improved. However, the point is not to discontinue an established and clinically effective therapy if disease clearance has not been achieved!"„

Crohn's disease – early and targeted treatment to change the course of the disease

„Within the first 5 years after diagnosis, the risk of progression and the frequency of surgery in MC increase steadily [11],“ reported Prof. Dr. med. Sebastian Zeißig, Greifswald, and added: „Early and effective therapy therefore probably has the potential to reduce the progression of intestinal damage and thus change the progressive course of the disease.“ [5,12-14] The results of the prospective, multicenter LOVE-CD study support this: With early initiation of therapy, i.e. with a shorter disease duration (< 2 years, biologics-naive), significantly higher rates of clinical and endoscopic remissions were achieved with vedolizumab than with initiation of therapy after a longer disease duration (> 2 years, biologics-experienced). [15] The use of vedolizumab as a first-line biologic [f] is also supported by real-world data, emphasized Zeißig: In the large German real-world study VEDOIBD, significantly more biologic-naive CD patients achieved steroid-free remission after 2 years with vedolizumab compared to TNFα antagonists. [16] Furthermore, the biologic-naive patients with vedolizumab showed significantly higher treatment persistence over 2 years, [16] according to Zeißig.

Ambitious treatment goals for MC can be achieved with vedolizumab

According to Zeißig's assessment, histological remission as a therapeutic goal for CD could be quite realistic with vedolizumab. According to an early publication of the LOVE-CD study in 2019, an analysis of paired biopsies with baseline inflammation at week 26 showed histological remission with a Geboes score < 3.1 in 64 patients (43/67) and a Robarts histopathology index of 6 (no granulocytes) in 66 patients (37/56). [17] In a post-hoc analysis of the VERSIFY study, vedolizumab therapy in CD patients with transmural inflammation present at baseline (including bowel wall edema, bowel wall thickness > 3 mm) reduced this inflammation after 26 and 52 weeks. [3]

Furthermore, the EVOLVE expansion study found that in biologic-naive CD patients, regardless of disease location, there were no significant differences in clinical response, clinical remission, mucosal healing, and treatment persistence over 36 months between vedolizumab and ustekinumab. [18]

CDST – Support in selecting therapy for MC

Not only early and effective treatment, but also its individualization is an important factor for optimized management of CD patients. A Clinical Decision Support Tool (CDST) has been developed specifically for vedolizumab, which incorporates five easily identifiable and patient-specific variables, explained Zeißig. [19] The algorithm enables the determination of the probability of treatment response to a 26-week course of vedolizumab treatment in CD patients. [19] [g]

source

Symposium "IBD Management: From Theory to Practice – What Are Realistic Goals?", September 19, 2025, as part of the DGVS Visceral Medicine 2025; Organizer: Takeda Pharma Vertrieb GmbH & Co. KG, Berlin

Explanations

[a] Vedolizumab is approved for the treatment of adult patients with moderately to severely active forms of ulcerative colitis/Crohn's disease who have had an inadequate response to, lost response to, or are intolerant to conventional therapy or one of the tumor necrosis factor alpha (TNFα) antagonists. [6,7]

[b] Clinical remission (partial Mayo score ≤ 2 and no individual subscore > 1 [excluding sigmoidoscopy subscore]) and endoscopic improvement (endoscopic Mayo subscore ≤ 1) and minimal histological disease activity (Robarts histopathology index < 5)

[c] Limitation: Deviating from the approved indication of vedolizumab, patients with mild disease activity were also included (group 3 [n = 213]: 4.7% [n = 10] of patients with mild UC).

[d] as observed data-set

[e] Primary endpoints: clinical and endoscopic remission (CDAI ≤ 150 and Simple Endoscopic Score for MC [SES-CD] < 4)

[f] First-line biologic: Its use is supported by the DGVS and ECCO guidelines.20,21

[g] More at www.takeda-gastroenterologie.de/cdst

credentials

1 Danese S et al. Nat Rev Gastroenterol Hepatol 2020; 17:1-2
2 Jairath V et al. J Crohn's Colitis 2025; 19(Suppl 1): 180-181
3 Rimola J et al. Clin Exp Gastroenterol 2024; 17:9-23
4 Turner D et al. Gastroenterology 2021; 160: 1570-1583
5 Noor NM et al. Lancet Gastroenterol Hepatol 2024; 9(5): 415-427
6 Summary of Product Characteristics Entyvio® 300 mg powder for concentrate for solution for infusion, current version
7 Summary of Product Characteristics Entyvio® 108 mg solution for injection in a pre-filled syringe/Entyvio® 108 mg solution for injection in a pre-filled pen, current version
8 Yoon H et al. Gastroenterology 2020; 159: 1262-1275.e7
9 Danese S et al. J Crohn's Colitis 2021; 15 (Supplement 1): S305-S305. P271
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21 Gordon H et al. J Crohn's Colitis 2024; 18(10): 1531-1555
22 Center for Drug Evaluation and Research (CDER) & the FDA. The Voice of the Patient/Functional Gastrointestinal Disorder; 2016. https://www.fda.gov/media/95140/download (last access: November 6, 2024)
23 Jones R et al. Br J Gen Pract. 2009; 59(563):e199-208