P521 Correlation of histological assessment of mucosal healing with long-term clinical and patient-reported outcomes in patients with moderately to severely active ulcerative colitis treated with upadacitinib: results from the Phase 3 U-ACHIEVE maintenance trial

Abstract

Abstract Background Establishing mucosal healing (MH) as a treatment goal for ulcerative colitis (UC) requires evidence of improvement in both endoscopic and histologic assessments of the intestinal mucosa and long-term sequalae. Currently, guidelines on how to interpret the histological index, Geboes Score (GS), with respect to clinically meaningful outcomes, are lacking. We examined the relationship between GS and long-term clinical and patient-reported outcomes in patients with active UC treated with upadacitinib. Methods GS and long-term clinical and patient-reported outcomes from the U-ACHIEVE maintenance trial (NCT02819635) were analysed. Patients were assigned to the following GS intervals [0, 2.0), [2.0, 3.1], and (3.1, 5.4]. The intervals were selected to assess patients who achieved the histology threshold for MH (<2.0) and those who achieved the histologic and endoscopic mucosal improvement threshold without MH [2.0, 3.1]. A predictive analysis (n=497) assessed the relationship between outcomes at Week 52 and GS intervals at end of induction (Week 8/16), and a cross-sectional analysis (n=211) examined outcomes at Week 52 and GS intervals at end of maintenance (Week 52). Odds ratios (ORs) with 95% confidence intervals (CIs) were derived from logistic regression adjusting for baseline characteristics. Results Adjusted ORs for long-term outcomes and GS intervals at Week 8/16 are provided in the Table 1. Patients with GS <2.0 at end of induction had a significantly higher likelihood of achieving clinical remission per adapted Mayo score (OR=1.8, p<0.030) and endoscopic improvement (OR=1.8, p<0.015) at Week 52 than patients with GS >3.1. Results were directionally similar, but not statistically significant, for all other outcomes. No significant differences were seen in the likelihood of achieving any outcome at Week 52 among patients with GS between 2.0 and 3.1 vs those with GS >3.1. Patients with GS <2.0 at Week 52 had a significantly greater likelihood of achieving all clinical endpoints and clinically meaningful improvements in UC-SQ, IBDQ, SF-36 PCS, and EQ-5D index scores at Week 52 compared to patients with GS >3.1 (Table 2). In patients with GS between 2.0 and 3.1 vs GS >3.1, results were numerically smaller than for patients with GS <2.0, and not significant for absence of rectal bleeding, low faecal calprotectin levels, and all patient-reported outcomes. Conclusion Evidence from the U-ACHIEVE maintenance trial of upadacitinib demonstrates that histological assessment of MH by GS at end of induction or maintenance is associated with long-term benefits, with GS <2.0 representing a relevant threshold for desirable clinical and patient-reported outcomes after one year of maintenance therapy.