DOP057 Early serum and faecal cytokines predict clinical outcomes in Acute Severe Ulcerative Colitis: results from PREDICT-UC
Authors: Li Wai Suen C , Choy M C , Cheng K , Con D , Nigro J , Breheney K , De Cruz P , Visvanathan K 
Published: January 2025

Abstract

Background
Acute severe ulcerative colitis (ASUC) is a medical emergency with variable outcomes. We aimed to evaluate whether early serum and faecal cytokine levels predict treatment response.

Methods
Serum and stool were collected from patients with ASUC. Steroid-refractory patients received infliximab (IFX, monoclonal antibody to tumour necrosis factor [TNF]) as part of PREDICT-UC (NCT02770040), a multi-centre randomised controlled trial that evaluated escalated infliximab (IFX) dosing.1 Specimens were collected at screening, and if steroid-refractory at days 1 and 3 post-IFX. Response to first IFX dose was assessed by day 7. Interleukin (IL)-6 and TNF levels were quantified using ELISA after clinical study conclusion.

Results
Within the cohort of 190 patients, 54 were steroid-responsive and 136 steroid-refractory and received IFX. Of the steroid-refractory patients, 85 (62.5%) were IFX responders and 51 (37.5%) were IFX non-responders. 17/136 (12.5%) patients underwent colectomy by 3 months.

Steroid response
At screening, serum IL-6 was higher in steroid non-responders compared to responders (10.5 pg/mL vs 3.5 pg/mL, P&lt;0.001), whereas faecal IL-6 was similar in both groups (154.7 pg/mL vs 138 pg/mL, P=0.09). Faecal TNF at screening was higher in non-responders compared to responders (48.6 pg/mL vs 14.6 pg/mL, P=0.032).

IFX response
Serum IL-6 at was higher in IFX non-responders compared to responders at all timepoints (P&lt;0.005); however, this finding was not observed with faecal IL-6. Whilst faecal TNF at screening, days 0 and 1 did not differ between IFX responders and non-responders, median day 3 faecal TNF was suppressed below detection limits (&lt;1.56 pg/mL) in IFX responders compared to 4.4 pg/mL in non-responders (P=0.006, AUC=0.65).

Colectomy by month 3
Higher serum IL-6 at screening (P=0.009, AUC=0.71) and day 1 (P=0.002, AUC=0.75) were associated with month 3 colectomy. Similarly, day 3 faecal IL-6 was higher in patients who required colectomy versus those who did not (159.0 pg/mL vs 110.7 pg/mL, P=0.02, AUC 0.69). Median faecal TNF at day 3 post-IFX was 6.3 pg/mL in patients who required colectomy but dropped below detection limit in those who avoided colectomy (P=0.004). Day 3 faecal TNF predicted colectomy (AUC=0.72) with a threshold of ≥7.07 pg/mL on Youden’s index having 50% sensitivity, 89.8% specificity, 43.8% PPV and 91.9% NPV.

Conclusion
Early serum and faecal cytokines predict outcomes in ASUC. Faecal TNF persistence 3 days after IFX is associated with non-response and colectomy, and might help identify patients who benefit from early IFX re-dosing. IL-6 elevation in non-responders suggests activation of an alternate immune pathway that may benefit from non-TNF-targeted therapy.

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.