S1063 Improvement in Inflammatory Biomarker Levels Through Week 12 in Moderately to Severely Active Ulcerative Colitis Patients Treated With Guselkumab: Results From the Phase 3 QUASAR Induction Study

Introduction: C-reactive protein (CRP) and fecal calprotectin (FeCal) are non-invasive inflammatory biomarkers used to assess disease activity in UC. The Phase 3 QUASAR induction study evaluated efficacy and safety of guselkumab (GUS), an IL-23 p19 subunit antagonist, in patients (pts) with moderately to severely active UC. Here, we analyze the effect of GUS treatment on CRP and FeCal through Week (Wk) 12 in pts with elevated CRP and/or FeCal at baseline (BL). Methods: Pts with a modified Mayo score of 5-9 and a Mayo endoscopy subscore ≥2 at BL were randomized 3:2 to receive either GUS 200mg IV or placebo (PBO) IV at Wks0, 4, and 8. CRP and FeCal were assessed at BL, Wk4, Wk8 (for CRP only), and Wk12. All analyses were not multiplicity controlled (nominal P-values). Results: Of 701 pts assessed, nearly 50% had a history of inadequate response/intolerance to advanced therapies (ADT) for UC; 47.4% of these pts had inadequate response/intolerance to ≥2 ADT classes. Median BL concentrations of CRP and FeCal were similar between the GUS- and PBO-treated pts (4.34 vs 3.83mg/L and 1651 vs 1606mg/kg, respectively). The proportions of pts with elevated CRP/FeCal at BL were similar between treatment groups. Compared with PBO, greater reductions in CRP and FeCal were observed with GUS at the earliest timepoint assessed (Wk4) and continued through Wk12 (Table 1). Among pts with elevated CRP ( >3mg/L), median change from BL in CRP concentration (mg/L) at Wk12 for the GUS and PBO cohorts were -3.99 and -0.51mg/L, respectively ( P< 0.001); the proportions of pts achieving 50% and 75% reduction in CRP levels (or ≤3mg/L) at Wk12 were higher for GUS-treated pts than those receiving PBO (59.7% vs 28.1% and 47.2% vs 19.4%; both P< 0.001). Among pts with elevated FeCal (>250mg/kg), median change from BL in FeCal concentration (mg/kg) at Wk12 were -800 and -86mg/kg for the GUS and PBO cohorts, respectively (P< 0.001); the proportions of pts achieving 50% and 75% reduction in FeCal levels (or ≤250 mg/kg) at Wk12 were higher for GUS-treated pts than those receiving PBO (51.1% vs 33.8% and 41.4% vs 23.6%; both P< 0.001). At Wk12, GUS-treated pts achieved CRP≤3mg/L and/or FeCal≤250mg/kg at higher rates than PBO-treated pts (Figure 1). Conclusion: Pts with moderately to severely active UC and elevated inflammatory markers treated with GUS 200mg IV induction showed greater improvement from BL in both CRP and FeCal levels compared with PBO. Differences were observed as early as the first assessments at Wk4 and continued through Wk12. Table 1. - Change from baseline in CRP and FeCal through Week 12 among patients with elevated CRP (>3mg/L) or FeCal (>250mg/kg) at baseline Placebo IV Guselkumab 200 mg IV CRP (mg/L) Baseline, N 160 248 Median [IQR] 8.02 [5.40; 16.85] 9.26 [5.31; 18.05] Wk 4, N 158 245 Median change from baseline [IQR] -2.06 [-5.70; 1.58] -3.35 [-8.60; -0.23]*** Wk 8, N 156 239 Median change from baseline [IQR] -1.75 [-5.68; 1.46] -3.80 [-10.77; -0.19]*** Wk 12, N 153 239 Median change from baseline [IQR] -0.51 [-4.64; 2.72] -3.99 [-11.46; -0.85]*** FeCal (mg/kg) Baseline, N 225 333 Median [IQR] 1743 [1120; 3395] 1787 [920; 4009] Wk 4, N 213 308 Median change from baseline [IQR] -227 [-1041; 658] -603 [-1866; 230]*** Wk 12, N 201 293 Median change from baseline [IQR] -86 [-1254; 504] -800 [-2532; 0]*** ***Nominal P≤0.001. 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 or other reasons except for COVID-19 related reasons (excluding COVID-19 infection) or regional crisis in Russia and Ukraine prior to the designated timepoint had their baseline value carried forward from the time of the event onward. The P-values of treatment comparison were based on the mixed-effect model repeated measures with CRP and FeCal values being log-transformed. Figure 1.: Proportions of patients achieving CRP ≤3 mg/L and FeCal ≤250 mg/kg through Week 12 among patients with elevated CRP (>3mg/L) or FeCal (>250mg/kg) at baseline.

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