P348 Increased pre-treatment faecal calprotectin concentration predicts resistance to ustekinumab induction in ulcerative colitis

Abstract

Abstract Background Rates of resistance to advanced therapy remain high in ulcerative colitis (UC). Pre-treatment predictors of poor outcomes would provide valuable information for treating clinicians so other therapies could be given or early treatment switches could be considered if response is inadequate. We investigated whether baseline, pre-treatment faecal calprotectin (FCP) can predict resistance to ustekinumab. Methods Clinical outcomes at week 8, including clinical remission, endoscopic healing and mucosal healing were determined in patients enrolled in the UNIFI phase 3 placebo-controlled trial program, investigating the efficacy of ustekinumab for moderate-to-severe UC (GSE206285), in whom FCP concentrations were available at baseline, prior to initiation of treatment. Clinical outcomes were defined in patients with FCP < 250mcg/g, 250 – 999mcg/g, 1000 – 1999mcg/g and >= 2000mcg/g. Chi-squared test was used to assess statistical significance. Area under the receiver operating characteristics curve (AUROC) analyses were used to determine the ability of faecal calprotectin level to predict treatment resistance. Analyses were performed using R 4.2.3 (Vienna, Austria) and GraphPad Prism 10.0.3 (Massachusetts, United States). Results Outcome data and linked faecal calprotectin levels were available for 340 patients. FCP values ranged from 15 – 25249mcg/g. The median FCP value was 1402mcg/g (interquartile range: 600.8 – 2772.0mcg/g). In general, all clinical outcome measures were progressively worse with increasing FCP concentrations. For the respective FCP cut-offs, 22.0%, 19.3%, 11.3% and 6.7% achieved clinical remission; 39.0%, 24.1%, 20.6% and 16.0% achieved endoscopic healing; and 29.3%, 16.9%, 15.5% and 7.6% achieved mucosal healing (Figure 1). ROC analyses revealed that pre-treatment FCP predicts resistance to ustekinumab therapy for all stated outcomes, including clinical remission (AUROC: 0.66, P=0.001), endoscopic healing (AUROC: 0.63, P=0.0013) and mucosal healing (AUROC: 0.65, P=0.0005). Conclusion Increasing concentrations of pre-treatment FCP predicts resistance to ustekinumab therapy in moderate-to-severe UC. Patients with FCP >= 2000mcg/g were significantly less likely than those with FCP <1000 mcg/g to achieve clinical remission or mucosal healing. Since neutrophils are the main producers of FCP, these data build on other emerging data indicating that excessive accumulation of mucosal neutrophils is associated with treatment resistance in IBD.