Introduction

The BIOSTOP Trial is a prospective, multicenter, randomized, controlled, open-label study conducted in Norway to evaluate the two-year outcomes of tumor necrosis factor-alpha (anti-TNF) antibody withdrawal in patients with ulcerative colitis (UC) in sustained clinical and endoscopic remission. Prior non-randomized studies have suggested that approximately half of such patients maintain remission after anti-TNF discontinuation and that reintroduction of anti-TNF therapy is generally effective and safe in the event of relapse.

Aims & Methods

A total of 174 UC patients in confirmed clinical and endoscopic remission were enrolled across 19 gastroenterology centers between June 2017 and December 2020 and randomized 1:1 to either continue or discontinue anti-TNF therapy. Eligibility criteria included at least 12 months of first-line anti-TNF maintenance treatment, clinical remission, fecal calprotectin <200 µg/g, and endoscopic remission (Mayo endoscopic score 0 or 1). Two-year follow-up data were available for 172 patients (86 in each group). In 156 of the patients endoscopies were available for central reading (77 in the withdrawal group and 79 in the maintenance group). The primary endpoint was sustained endoscopic remission at two years.

Results

At two years, central reading of follow-up colonoscopies confirmed endoscopic remission in 64 of 77 patients (83%, 95% CI 71.8 – 93.1) in the anti-TNF withdrawal group, compared to 77 of 79 patients (96 %, 95 % CI 92.1 – 100.8) in the anti-TNF maintenance group. The non-inferiority primary endpoint of the study was thus not met. During the study period, 48% of patients in the withdrawal group and 88% in the maintenance group remained in sustained clinical and endoscopic remission without relapse. Among the 45 patients in the withdrawal group who experienced endoscopic confirmed relapse, 28 (62%) resumed anti-TNF therapy, with 26 achieving both clinical and endoscopic remission. Additionally, 10 of 13 patients with mild relapses achieved endoscopic remission with optimized non-biologic therapy. There were no difference in serious adverse events between the groups.

Conclusion

After two years, 83% of patients in the anti-TNF withdrawal group and 96% in the maintenance group were in clinical and endoscopic remission, including those who experienced flares and achieved new remission after reintroduction of anti-TNF or optimized non-biologic therapy. Nearly half of the patients maintained remission without anti-TNF, and the majority of relapses were effectively managed. These findings suggest that anti-TNF withdrawal is a safe option for selected UC patients in confirmed remission, provided they are monitored closely.
Trial Registration: ClinicalTrials.gov Identifier: NCT03011268; EudraCT Number: 2016-001409-18. Trial completion date: 31 January 2025.

Disclosure

No disclosures

Introduction

Resection rates for Crohn's disease (CD) have decreased over time, while re-resection rates have remained stable at about one-third in historic cohorts. Medical treatment has been shown to influence the course of the disease.

Aims & Methods

We aimed to assess the impact of disease burden categorization on medication use and risk factors. This cohort study encompassed all CD patients undergoing primary intestinal resection in Eastern Denmark from 2010 to 2020 (46% of the Danish population, n=2,730,000). We isolated all patients with five years follow up and divided them into three groups based on post-operative disease burden: high (one or more resections after the initial resection), intermediate (recurrence without need for resection), and low (no recurrence within five years). Disease recurrence was defined based on colonoscopy (SES-CD≥3, Rutgeerts score ≥i2), inflammation or stenosis on imaging (MRI, CTA, IUS), fecal calprotectin ≥ 250 mg/kg, starting corticosteroids or re-resection due to disease activity. Medication was classified by potency, with each patient assigned to only one category (no therapy<corticosteroids<immunomodulators<biologics). We used nonparametric statistics and the Kruskal-Wallis test to compare outcomes across groups.

Results

Primary resection was performed on 631 patients due to disease activity. Patients were categorized into burden groups: high burden (n=59), intermediate (n=287), and low (n=170). The median age at diagnosis was 28.2 years (range: 21.6-43.9), with no significant differences between the three disease burden groups (p=0.069). Age at primary resection differed across groups: 38 years (25-53) for high burden, 32 (24-45) for intermediate, and 36 (27-47) for low burden (p=0.019). Smoking rates were highest in the high burden group (47%) versus intermediate (37%) and low (27%) (p=0.010).
Pre-resection medical consumption was similar across the three burden groups (p=0.2). Postoperatively, the high burden group used more biologics (54%) compared to the low burden group (16%). Additionally, 57% of the low burden group remained recurrence-free and unmedicated for five years (Table 1). In the high burden group, no patients received prophylactic biologics, compared to 8% in the intermediate and low burden groups (p=0.001). Disease location varied: colon resections were most common in the high burden group (31%), and small bowel disease, including ileocecal resections, predominated in the low burden group (47%) (p<0.001). Strictures were more common in the intermediate and low burden groups, while luminal disease was mostly seen in the high-risk group (p=0.046) (Table 1)

Table 1. Medical characteristics and Montreal classification

Conclusion

High burden patients relied more on biologics, while half of the low burden patients stayed recurrence-free unmedicated for five years, suggesting tailored treatments could improve post-resection CD management.