Early use of biologics in ulcerative colitis and Crohn's disease to achieve therapeutic goals
27.04.2023 16:39
– The treatment strategies and goals as well as diagnostic methods for ulcerative colitis (UC) and Crohn's disease (CD) have changed over the years. Experts discussed where this development has reached today and what the choice of suitable therapeutic strategies may look like in the future at two symposia supported by Takeda on the occasion of the 18th Congress of the European Crohn's and Colitis Organization (ECCO) in Copenhagen.
According to Prof. Axel Dignaß, Frankfurt/Main, the desired goals went “ever deeper” and were set ever more narrowly: from clinical remission to endoscopic to histological (for UC) or transmural (for MC) remission as supplementary measures to measure the depth of remission (6). According to the STRIDE II (Selecting Therapeutic Targets in Inflammatory Bowel Disease) recommendations from 2021, a rapid response (symptom control) and, in the medium term, a clinical remission with normalization of C reactive protein (CRP) and fecal calprotectin (FCP) and, in the long term, an endoscopic one would have to be achieved healing can be achieved. In addition, a normalized quality of life and the absence of disabilities would be required as long-term therapy goals (2). The SPIRIT initiative (Selecting End Points for Disease-Modification Trials) recommends placing even more emphasis on PROs, including health-related quality of life, possibly fecal incontinence or disability. In addition, medium and long-term complications - from IBD-related operations to
to cancer – can be avoided. However, the SPIRIT recommendations still need to be validated in clinical studies before they can be implemented in disease modification studies.
Early disease clearance as a new therapeutic goal
“In order to achieve the best possible long-term outcome for patients with ulcerative colitis, disease clearance consisting of symptomatic (based on PROs), endoscopic and histological remission (mucosal healing) should be aimed for in the future,” reported Prof. Fernando Magro, Porto/Portugal ( 1). Histological remission in particular is important because histological endpoints have proven to be informative in studies (10). Persistent histological disease activity in UC may also be associated with a higher risk of recurrence (11). In addition, according to a work by Yoon et al. In UC patients with an endoscopic plus histological remission, the risk of recurrence is significantly lower than in patients who only achieved a clinical remission (12). “Histology is a strong predictor of disease progression in UC,” emphasized Magro. If neutrophils are present in the epithelium as well as mucosal erosions or ulcers, then the FCP values are increased. Thus, the presence of neutrophils in the epithelium is the main marker for histological disease activity (13). The aim is to achieve disease clearance in a UC patient, explained Magro. An important part of this is the histological disease activity, which can be a risk factor for disease progression (3). In addition, disease clearance, if achieved early, can be associated with a significantly reduced risk of hospitalization and surgery (4). “Early disease clearance could therefore represent a new valid combined endpoint in UC management,” summarized Magro
Early initiation of therapy for Crohn's disease to avoid complications and recurrences
Even with Crohn's disease, the treatment goals should be achieved as quickly as possible. This requires sequential treatment according to the course of the disease, explained Prof. Shomron Ben-Horin, Tel-Aviv/Israel. Together with Prof. Séverine Vermeire, Leuven/Belgium, he explained therapy sequencing for MC based on a patient case. Studies have shown that uncontrolled MC leads to damage to the intestinal tissue with complications, e.g. B. ulcerations and strictures.12 This would include, among other things, the involvement of the ileum,
Perianal involvement and deep and extensive ulcerations have been shown to be risk factors for later complications (14-16). In any case, early initiation of therapy is crucial in CD in order to slow disease progression (5,17-19). There is increasing evidence that the early use of biologics after conventional therapy for CD is associated with higher rates of clinical remission and mucosal healing as well as lower recurrence rates and fewer operations (17.1).
CD patients may benefit from early use of vedolizumab
There are now an increasing number of treatment options for IBD, says Ben-Horin. These included anti-TNFα therapies (infliximab, adalimumab, golimumab), the α4β7 integrin antagonist vedolizumab, the IL-12/23 antagonist ustekinumab and small molecules. The fact that CD patients can benefit from early use of vedolizumab, for example, was highlighted by the real-world data from the US VICTORY consortium: Vedolizumab therapy started in the early stages (≤ 2 years) of CD in biologics-naïve patients
Patients achieved better results in terms of clinical, corticosteroid-free and endoscopic remission compared to starting only after a longer duration of illness (> 2 years).19
In addition to drug therapy, dietary measures are often recommended for CD patients, Vermeire added. "There are a variety of different diet plans, but so far there is no consensus as to which foods (ingredients) should be avoided and which should be preferred in MC."
Patient case reports - therapy sequencing with vedolizumab as a first-line biologic
The patient presented by Ben-Horin and Vermeire, a smoker, suffered from diarrhea, abdominal pain, weight loss and fatigue for 3 months. C-reactive protein (CRP) and fecal calprotectin (FCP) were increased, iron decreased. Colonoscopy and magnetic resonance enterography revealed nonstenosing, nonpenetrating MC with mucosal ulcers and 15 cm long involvement of the terminal ileum and cecum. After systemic and local corticosteroid therapy, there was initially a significant improvement in symptoms, but 15 weeks after tapering off the steroids, severe diarrhea and abdominal pain recurred. Sonography revealed wall thickening of the terminal ileum, increased vascularization, and proximal dilatation. An ileocecal resection was then performed. No postoperative prophylaxis was started because the patient had no symptoms and an overall improved quality of life. However, after 6 months, colonoscopy revealed a narrowed ulcerated anastomosis and occasional small ulcers in the small intestine. Therapy with vedolizumab 300 mg iv as a first-line biologic has now been started. Clinical remission, normalization of biomarkers (CRP and FCP) and healing of all ulcers occurred quickly
regular anastomosis. The patient also reported a good quality of life again. The treatment was changed to the subcutaneous (sc) formulation of vedolizumab8 after 6 months in consultation with the patient. Efficacy and safety of vedolizumab sc as maintenance therapy for moderately to severely active CD were demonstrated in the VISIBLE-2 trial, Vermeire reported ( 20 ). “This means that the patient now has more freedom of action in her treatment.”
“When choosing the first-line biologic, a risk-benefit balance must be made between effectiveness and tolerability. It is also important to inform the patient about the therapy goals and therapeutic options so that a decision can be made together with them. This is the only way the therapy goals can be achieved,” emphasized Vermeire and Ben-Horin in conclusion (21,22).
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