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