842 Impact of Response and Inflammatory Burden at Start of Maintenance Therapy on Clinical Efficacy of Ustekinumab Dosing Regimen in UC: Week 44 Results From UNIFI

Abstract

INTRODUCTION: The UNIFI maintenance study was a Phase 3, double-blind, placebo-controlled, randomized-withdrawal study in pts with moderate to severely active ulcerative colitis (UC) who failed conventional or biologic therapy and were in clinical response 8 wks after receiving a single ustekinumab (UST) IV induction dose. In this study, pts were randomized to placebo, UST 90 mg SC q8w or q12w. METHODS: To examine the relative efficacy of the UST 90 mg SC q8w or q12w maintenance regimens, subgroup analyses were performed for outcomes of clinical remission, symptomatic remission, and endoscopic improvement at Wk44 for pts who did and did not achieve these endpoints at the start of maintenance. Analyses of clinical remission and endoscopic improvement at Wk44 based on pre-specified cut-points of the concentrations of inflammatory biomarkers (CRP [≤3 mg/L, >3 mg/L] and fecal calprotectin [≤250 mg/kg, >250 mg/kg]) at maintenance baseline were also conducted. RESULTS: For pts who had achieved clinical remission, symptomatic remission, or endoscopic improvement at maintenance baseline, efficacy of UST q8w and q12w regimens for the respective endpoint at Wk44 was similar (Table 1). By contrast, for pts who did not achieve clinical or symptomatic remission or endoscopic improvement at maintenance baseline, UST q8w demonstrated greater efficacy than UST q12w for that endpoint at Wk44. Pts with low inflammatory burden marked by CRP ≤3 mg/L at maintenance baseline achieved similar efficacy at Week 44 with UST q8w and q12w dosing regimens as measured by clinical remission and endoscopic improvement (Table 1). By contrast, pts with high inflammatory burden, marked by CRP >3 mg/L at maintenance baseline, achieved greater efficacy at Wk44 with UST q8w versus q12w dosing over the endpoints. Generally similar trends were seen in pts with fecal calprotectin measurements for low (≤ 250 mg/kg) and high (>250 mg/kg) inflammatory burden at maintenance baseline. CONCLUSION: Among pts with a clinically meaningful response to a single IV induction dose of UST, maintenance treatment with UST q8w or q12w demonstrated similar efficacy at Wk44. By contrast, the efficacy of UST q8w at Week 44 was greater than the q12w regimen for pts with higher inflammatory burden or who did not achieve clinical or symptomatic remission or endoscopic improvement at Wk8. These data suggest that multiple clinical measures can help inform the decision on the most appropriate maintenance dosing regimen for UST in the treatment of pts with UC.