P0698 Early faecal calprotectin predicts clinical outcomes in Acute Severe Ulcerative Colitis: results from PREDICT-UC
Authors: Li Wai Suen C , Choy M C , Con D , Driver K , Bruen D , Glason J , Bonelli F , Boyd K , Pena R , Burrell K , Rosella O , Proud D , Brouwer R , Gorelik A , Liew D , Connell W , Wright E , Taylor K , Pudipeddi A , Sawers M , Christensen B , Ng W , Begun J , Radford-Smith G , Garg M , Martin N , van Langenberg D , Ding N , Beswick L , Leong R , Sparrow M , De Cruz P 
Published: January 2025

Abstract

Background
Faecal calprotectin (FCP) is routinely used in the management of inflammatory bowel disease; however, its role in acute severe ulcerative colitis (ASUC) is unclear. We aimed to evaluate the relationship between FCP and outcomes in ASUC.

Methods
We included ASUC patients who were screened/randomised as part of PREDICT-UC (NCT02770040), a randomised controlled trial that evaluated escalated infliximab (IFX) dosing strategies in steroid-refractory ASUC.1 Stool was collected at screening, and in steroid-refractory patients at day 0 (pre-IFX), and days 1, 3, 5, 7, 14, 30 and 42 and months 3, 6, 9 and 12 post-IFX. FCP was quantified by Liaison® XL (Diasorin) and correlated with outcomes. Outcomes included initial IFX response by day 7 (Lichtiger score&lt;10, with ≥3-point reduction and decrease in rectal bleeding and stool frequency ≤4/day), month 3 colectomy and month 3 Mayo remission (partial Mayo ≤1 & Mayo endoscopic score ≤1).

Results
Of 185 patients with ASUC, 49 were steroid responders while 136 were steroid-refractory and received IFX. Of 136, 85 were initial IFX responders and 17 required colectomy by month 3.
Screening FCP was higher in steroid-refractory compared to steroid responsive patients (median [IQR] 3745 [1753-6175] ug/g vs 2305 [826-4400] ug/g, P=0.020).
In steroid-refractory patients, day 0 FCP did not correlate with the Mayo endoscopic score or Ulcerative Colitis Endoscopic Index of Severity (UCEIS) but correlated with CRP (rho=0.251, P=0.031) and the erosion/ulcer sub-score of the UCEIS (rho=0.298, P=0.010).
In linear mixed modelling, FCP dynamics in the first 3 days differed between IFX responders and non-responders (daily 22% decrease [95% CI 13 to 31%] vs 3% decrease [95% CI -12 to 16%], P=0.018). A higher day 3:day 0 FCP ratio predicted initial IFX non-response (median [IQR] 109 [51-158] % vs 57 [21-92] %, P=0.006, Area under receiver operator characteristic curve [AUROC]=0.72).
FCP dynamics in the first 2 weeks after IFX differed in patients who avoided vs required colectomy (weekly 59% decrease, 95% CI 52 to 65% vs 6% decrease, 95% CI -76 to 50%; P=0.012). Month 3 colectomy was predicted by a higher day 7 FCP (AUROC 0.71, 95% CI 0.49-0.92, P=0.044) and a higher day 3:day 0 FCP ratio (AUROC 0.75, 95% CI 0.58-0.91, P=0.018). Mayo remission at 3 months was predicted by lower day 14 FCP (AUROC 0.31, P=0.004) and day 14:day 0 ratio (AUROC 0.27, P=0.006).

Conclusion
FCP level and dynamics are novel predictors of outcomes in ASUC. Decrease in FCP by day 3 after IFX predicts initial response. Absolute day 7 FCP and early dynamics predict colectomy. Absolute day 14 FCP and FCP dynamics by day 14 predict month 3 Mayo remission and may help identify patients who may benefit from treatment optimisation.

References
1.Choy MC, Li Wai Suen CFD, Con D, et al. Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial. Lancet Gastroenterol Hepatol 2024; 9(11): 981-96.