Assessment of Fecal Markers and Clinical Outcomes in Patients With Moderately to Severely Active Ulcerative Colitis: Results from PURSUIT-SC Induction

Abstract

Introduction: Assess changes in fecal inflammatory markers, calprotectin (fCal) and lactoferrin (fLac), relative to clinical outcomes at week 6 in ulcerative colitis (UC) from PURSUIT-SC induction golimumab (GLM). Methods: Phase 3 portion of PURSUIT-SC was a multi-center, randomized, placebo (PBO)-controlled double-blind study to evaluate induction therapy with SC GLM. Patients with Mayo scores of 6-12 inclusive, including endoscopic subscore >2 were randomized to PBO/PBO, GLM 200 mg/100 mg, or GLM 400 mg/200 mg at weeks 0 and 2. Clinical response (CR) and other efficacy endpoints were assessed at week 6. Stool samples were collected for fCal and fLac at week 0 through week 6. Assays for fCal and fLac concentrations were done using validated methods. Cut-off baseline (BL) values were: fCal<or>250 mg/kg and fLac<or>7.5 μg/mL for analysis of week 6 efficacy. Absolute median changes in fecal markers were assessed for patients achieving CR and mucosal healing (MH) vs. those who did not. Results: At week 6, 53% vs. 30% and 44% vs. 29% of GLM vs. PBO patients were in CR and MH, resp. Median (IQ range) baseline concentrations for PBO and combined active groups, respectively, were: fCal 858 mg/kg (327,1810) and 843 mg/kg (358,1769); fLac 215 μg/mL (60,524) and 220 μg/mL(70,508). Patients with baseline fCal levels <250 mg/kg were more likely to be in CR and achieve MH at week 6 with GLM vs. those who had higher baseline fCal levels ≥250 mg/kg. Generally similar patterns were observed for the association of baseline fLac levels. There was no apparent effect of baseline fCal levels on PBO response; however, patients with fLAc <7.5 μg/mL tended to have higher PBO response at week 6 for CR and MH vs. those with levels >7.5 μg/mL (Table 1). Regardless of treatment, median decrease in fCal levels at week 6 was greater in patients with CR vs. those who did not achieve CR(PBO-369 mg/kg, combined GLM-298 mg/kg vs. PBO 0 mg/kg, combined GLM-113 mg/kg); similar results were observed among those who achieve MH vs. those who did not (PBO-309 mg/kg,combined GLM-370 mg/kg vs. PBO 0 mg/kg, combined GLM-114 mg/kg). Similar trends were observed with fLac (CR:PBO-72 μg/mL, combined GLM-44 μg/mL vs. PBO 0 μg/mL, combined GLM-20 μg/mL; MH: PBO-54 μg/mL, combined GLM 19 μg/mL vs. PBO 0 μg/mL, combined GLM-4 μg/mL).Table 1: Proportion of patients in clinical response and mucosal healing at week 6 by baseline fecal marker cut-off concentrationsConclusion: Patients with BL fCal levels <250 mg/kg are more likely to achieve CR&MH with GLM. A similar association was not observed for baseline fLac. Fecal markers were more likely to be improved in UC patients who were in CR and demonstrated MH after treatment. Disclosure - William J Sandborn, Brian G. Feagan, Jean-Frederic Colombel, Walter Reinisch, Peter Gibson, Judith Collins, Dino Tarabar, Zbigniew Hebzda, and Paul Rutgeerts-Janssen Scientific Affairs, LLC-all received Grant/Research support. Colleen Marano, Richard Strauss, Jewel Johanns, and Hongyan Zhang-all Janssen Scieitific Affairs, LLC employees. This research was supported by an industry grant from Janssen R&D, LLC.