OBJECTIVES: Treatment failure remains challenging in clinical practice among patients with ulcerative colitis (UC) receiving biologics. With limited real-world data on preferential sequencing, we evaluated outcomes of patients switching to another tumor necrosis factor inhibitor (TNFi) or non-TNFi biologic therapy following failure on first-line (1L) TNFis.

METHODS: Adult patients with ≥1 inpatient or ≥2 confirmed outpatient UC diagnoses (ICD-10: K51.-) and no subsequent Crohn’s disease diagnosis (ICD-10: K50.-) between 01/05/2014 and 30/06/2021 were identified from the German AOK PLUS administrative claims dataset, covering >3.4 million insured individuals. Bio-naïve patients initiating TNFis (infliximab, adalimumab, golimumab) in the inclusion period and switching to another biologic were selected. Patients were classified as within-class switchers (WCS) if they switched to a different TNFi or outside-class (OCS) if they switched to a biologic with an alternative mode of action (vedolizumab, ustekinumab; index = date of switch). Patients were followed from index to earliest of death, insurance end, or study end (30/06/2022). Cox regression models weighted using propensity score inverse probability of treatment weighting (IPTW) were utilized, comparing time to discontinuation, second switch, and prolonged corticosteroid therapy (3 prescriptions within 12 months).

RESULTS: Overall, 166 patients initiating TNFis and switching to another biologic were identified (mean 42.9 years, 49.4% female, mean 3.4 years follow-up). After IPTW, there were 71 and 76 patients in the WCS and OCS group, respectively. WCS were significantly more likely to discontinue therapy (Hazard Ratio [HR] 1.82, 95% Confidence Interval [CI] 1.14-2.89, p=0.012) and switch to a third therapy (HR 3.46, 95% CI 1.89-6.36, p<0.001). While WCS showed an increased likelihood to initiate prolonged corticosteroid therapy (HR 1.42, 95% CI 0.77-2.59, p=0.260), results were not significant.

CONCLUSIONS: This study suggests that following 1L TNFi failure, patients with UC exhibit more favourable outcomes when switching outside-class to a non-TNFi advanced therapy compared to a different TNFi.