Histology could become part of the therapy goals for ulcerative colitis in the future

13.11.2023 18:05

Due to the constant improvement of treatment strategies and diagnostic methods, the therapeutic goals for ulcerative colitis (UC) have continued to develop over the years. Experts discussed how the long-term outcome of UC patients can be improved and what importance histology could play in the future at a symposium supported by Takeda on the occasion of the United European Gastroenterology (UEG) Week 2023 in Copenhagen.

Therapy goals for UC continue to evolve and go “ever deeper”

“Ulcerative colitis is a progressive disease with a very variable but often unfavorable course,” explained Prof. Fernando Magro, Porto/Portugal. [1,4] It has been shown that the clinical symptoms may not accurately reflect the disease state, because even if UC is “silent” on the endoscopic level, disease activity can still exist microscopically. [5] One indication of this is the continued high hospitalization and operation rates among UC patients, despite the increasingly frequent achievement of clinical remission, emphasized Magro. [6] Not least for this reason, the therapeutic goals have evolved and gone “ever deeper”: from clinical remission to endoscopic remission to histological remission as a supplementary measure to measure the depth of remission. [9] According to the STRIDE II recommendations (Selecting Therapeutic Targets in Inflammatory Bowel Disease) from 2021, a rapid response (symptom control) and, in the medium term, clinical remission with normalization of C-reactive protein (CRP) and fecal calprotectin (FCP) would have to be achieved ) and long-term endoscopic healing can be achieved. In addition, a normalized quality of life and the absence of disabilities would be required as long-term therapy goals. [10] The SPIRIT initiative (Selecting End PoInts for Disease-ModIfication Trials) also recommends placing even more emphasis on patient-reported outcomes (PRO), including health-related quality of life, possibly fecal incontinence or disability. In addition, medium and long-term complications – from IBD-related operations to cancer – would have to be avoided. [9]

Early disease clearance as a future therapeutic goal

“In order to achieve the best possible long-term outcome for patients with ulcerative colitis - including preservation of quality of life and prevention of disabilities and long-term complications - it should be considered whether disease clearance in the future should consist of symptomatic (based on PROs), endoscopic and histological remission should be aimed for," explained Prof. Bruce Sands, New York/USA. [1] “Early disease clearance could represent a new valid combined endpoint in UC management,” Sands continued. [11] Particular attention must be paid to histological disease activity, he agreed with Magro. “Histology can be a strong predictor of disease progression in UC.” [2]

Risk factor histological disease activity

Prof. Alessandro Armuzzi, New York/USA, underlined this with the results of a prospective multicenter study: Histological disease activity was identified as the only risk factor that predicted clinical recurrence (odds ratio 4.29; 95 % confidence interval 1.55 - 11 .87; p = 0.005). [12] In addition, a meta-analysis of 17 studies with 2,608 UC patients showed that when an endoscopic and histological remission was achieved, the risk of recurrence was significantly lower than with clinical remission alone, emphasized Armuzzi. [13] According to Armuzzi, FCP and neutrophils are groundbreaking for the assessment of histological disease activity: “FCP values are increased when neutrophils are present in the epithelium and the intestinal mucosa has erosions or ulcers - regardless of which scoring system is used. The presence of neutrophils in the epithelium is therefore the main marker for histological disease activity.” [14] Sands added: “The FCP concentration also appears to be a predictor of the long-term outcome of the patients: FCP values ≤ 250 μg/g after the induction phase were compared to values > 250 μg/g with an associated with a higher probability of durable clinical, endoscopic and histological remission at week 52. This was the result of a post-hoc analysis of several studies of vedolizumab in patients with moderately to severely active UC.” [15]

VARSITY – Advantages for vedolizumab vs. adalimumab in UC

Histological response was also examined in VARSITY16, the first head-to-head study of two biologics for the treatment of UC, Sands explained. VARSITY initially demonstrated superiority of the α4β7 integrin antagonist vedolizumab over the TNFα antagonist adalimumab at week 52 in terms of clinical remission and mucosal healing in adult patients with moderately to severely active UC. [16] Minimal histological disease activity (RHI ≤ 4 or Geboes score ≤ 3.1)3 and complete histological remission (Geboes score < 2, RHI < 3)16 were also more frequently detected with vedolizumab at week 52 than with adalimumab . Furthermore, in a post hoc analysis, more patients receiving vedolizumab achieved histologic remission (Geboes score < 2 or RHI ≤ 2) plus endoscopic improvement (endoscopic Mayo subscore ≤ 1) at week 52 than patients receiving adalimumab group (RHI: vedolizumab 30.5 % vs. adalimumab 14.5 % or Geboes: 25.6 % vs. 6.7 %). [3]

With the modern therapies available today, a histological remission can be achieved in UC patients and, in some patients, a combination of histological remission and endoscopic improvement.3,16 However, prospective studies are still needed To validate histology as a further component of the treatment goals for UC, according to the speakers' final assessment.

literature

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7 Technical information Entyvio® 300 mg powder for a concentrate for the preparation of an infusion solution, current status
8 Technical information Entyvio® 108 mg solution for injection in a pre-filled syringe/Entyvio® 108 mg solution for injection in a pre-filled pen, current status
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17 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
18 Jones R et al. Br J Gen Pract 2009; 59(563): e199-208