S817 The Effect of Guselkumab Induction Therapy on Inflammatory Biomarkers in Patients With Moderately to Severely Active Ulcerative Colitis: QUASAR Phase 2b Induction Results Through Week 12

Introduction: C-reactive protein (CRP) and fecal calprotectin (FeCal) are non-invasive inflammatory biomarkers used to assess disease activity in patients with inflammatory bowel disease (IBD). Here we report inflammatory biomarker results through Week 12 for QUASAR (NCT04033445) Phase 2b Induction. QUASAR is a randomized, double-blind, placebo-controlled study of guselkumab (GUS), an interleukin-23 p19 subunit antagonist, in patients with moderately to severely active UC who had an inadequate response or intolerance to conventional (ie, thiopurines or corticosteroids) or advanced therapy (ie, tumor necrosis factor alpha antagonists, vedolizumab, or tofacitinib). Methods: Patients with moderately to severely active UC (defined as a modified Mayo score of 5 to 9, inclusive with a Mayo rectal bleeding subscore ≥ 1 and a Mayo endoscopy subscore ≥ 2 obtained at baseline [BL]) were randomized 1:1:1 to receive IV GUS 200 mg, 400 mg, or placebo at Weeks 0, 4, and 8. CRP and FeCal were assessed at BL and through Week 12. Results: Three hundred thirteen patients were included in the analysis; approximately 50% had a history of inadequate response/intolerance to advanced therapies. Median BL CRP and FeCal concentrations were similar across treatment groups. Greater median reductions in CRP and FeCal were observed at the earliest timepoint assessed (Week 4) with GUS and continued to Week 12 compared with placebo (Table). Median changes from BL to Week 12 in CRP were -1.86 mg/L for the combined GUS group compared with 0.06 mg/L for placebo (nominal p< 0.001). Median changes from BL to Week 12 in FeCal were -684.00 mg/kg and 0.00 mg/kg for the combined GUS group and placebo, respectively (nominal p< 0.001). At Week 12, higher proportions of patients treated with GUS compared with placebo had normalized CRP ≤3 mg/L (44.2% vs 18.8%, nominal p< 0.001), and normalized FeCal ≤250 mg/kg (33.0% vs 9.9%, nominal p< 0.001), respectively, among patients with abnormal CRP or FeCal at BL. Conclusion: Patients with moderately to severely active UC who received GUS IV induction treatment had greater reductions in CRP and FeCal concentrations through Week 12 compared with placebo with no dose dependent effect for GUS 200 mg and 400 mg. Reductions in CRP and FeCal were observed as early as Week 4 with GUS and continued to Week 12. Higher proportions of patients had normalized CRP and normalized FeCal levels at Week 12 with GUS compared with placebo. Table 1. - Change from baseline in CRP and FeCal concentrations through Week 12 Placebo IV(N=105) Guselkumab 200 mg IV (N=101) Guselkumab 400 mg IV(N=107) Guselkumab Combined (N=208) CRP (mg/L) Baseline, NMedian (IQR) 1054.89 (1.35; 10.80) 994.31 (1.61; 17.80) 1044.38 (1.88; 8.81) 2034.37 (1.74; 11.90) Change from baseline at Week 4, NMedian (IQR) 1040.00 (-1.32, 1.37) 98-2.18 (-8.60;-0.28)** 101-1.15 (-5.45; -0.06)** 199-1.45 (-6.69; -0.17)** Change from baseline at Week 8, NMedian (IQR) 1030.00 (-2.49; 1.74) 94-2.60 (-9.30; -0.39)** 102-1.55 (-4.80; -0.18)** 196-2.10 (-7.49; -0.23)** Change from baseline at Week 12, NMedian (IQR) 1020.06 (-2.23; 2.94) 97-2.31 (-8.20; -0.33)** 100-1.06 (-4.76; 0.07)** 197-1.86 (-6.28; -0.06)** FeCal (mg/kg) Baseline, NMedian (IQR) 911457.00(749.00; 3054.00) 951667.00(771.00; 2859.00) 1011578.00(811.00; 2860.00) 196 1619.50(791.00; 2859.50) Change from baseline at Week 4, NMedian (IQR) 89-116.00(-830.00; 812.00) 89-358.00 (-1641.00; 226.00) 95-391.00 (-1301.00; 167.00)* 184-378.00 (-1503.00;207.00)* Change from baseline at Week 12, NMedian (IQR) 770.00(-855.00; 1089.00) 82-745.00(-1946.00; 0.00)** 88-558.50(-1426.00; -12.50)** 170-684.00 (-1682.00, -10.00)** Patients who had a prohibited change in UC medication, an ostomy or colectomy, or discontinued study agent due to lack of efficacy or an AE of worsening of UC prior to the designated timepoint had their baseline value carried forward from the time of the event onward. Data after a discontinuation of study agent due to COVID-19 related reasons (excluding COVID 19 infection) were considered to be missing.*Nominal P< 0.05**Nominal P< 0.001

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