P0795 Clinical symptoms, C-reactive protein and albumin at admission to hospital poorly correlate with refractoriness to intravenous steroids in Acute Severe Ulcerative Colitis – posthoc analysis of the IASO trial
Authors: Drobne D , Vaja S , Qian W , Pavey H , Subramanian S , Brezina B , Steel A , Speight A , Lamb C , Sebastian S , Din S , Arnott I , Galea J , Hendy P , Selinger C , Steed H , Jairath V , Parkes M , Kaser A , Raine T 
Published: January 2025

Abstract

Background
Intravenous corticosteroids (IVCS) remain the cornerstone of treatment for patients admitted to hospital with Acute Severe Ulcerative colitis (ASUC). Unfortunately, up to one third of patients do not respond to IVCS and need medical or surgical rescue treatment. Identifying patients who are unlikely to respond to IVCS at the point of admission would be clinically relevant since these patients could be offered early rescue treatment, potentially reducing morbidity.

Methods
This was a post-hoc analysis of a UK multicentre, randomised placebo-controlled trial of Interleukin 1 blockade in Acute Severe Ulcerative Colitis (the IASO trial).1,2 The intervention group did not differ from placebo treated patients in terms of need for rescue therapy or colectomy. Therefore we pooled both groups in this post-hoc analysis. We studied whether clinical symptoms as captured by the modified Truelove and Witts severity index (MTWSI) or its individual components or biochemical parameters at admission to hospital could predict response to IVCS.

Results
Among 106 randomised patients 68/106 (64%) patients responded to IVCS. 38/106 (36%) were non-responders to IVCS and needed medical rescue treatment (32 infliximab, 6 ciclosporin). Median time to rescue therapy was 4 days (interquartile range: 3-6 days). We observed no differences in baseline MTWSI score or in its individual components (Figure 1) between IVCS responders compared to IVCS non-responders. Baseline median C-reactive protein (CRP) (31.9 mg/L Vs 29.5 mg/L, p= 0.8) and baseline median albumin (36.5 g/L vs 35.0 g/L, p=0.4) were similar between IVCS responders and non-responders. Numerically, patients with higher baseline albumin were less likely to be non-responders to IVCS (upper quartile serum albumin: ≥40.0 g/L, non-responders 23% vs lower 3 quartiles 39% non-responders; p=0.17). 9 patients needed colectomy by day 98, all of whom had a baseline albumin below this threshold. Sensitivity analyses restricted to subpopulations of patients already on oral steroids at admission, those with a new diagnosis of ulcerative colitis, and those randomised to placebo vs anakinra yielded similar results.

Conclusion
Baseline clinical symptoms at hospitalisation (modified Truelove and Witts severity index and its individual components) and biochemical parameters (CRP and albumin) did not identify patients refractory to IVCS in the IASO trial. These findings suggest that response to IVCS in ASUC cannot be predicted from baseline clinical symptoms and biochemical parameters at admission to hospital. All colectomies occurred in patients with baseline albumin below 40 g/L.

References
1.Thomas, M. G. et al. Trial summary and protocol for a phase II randomised placebo-controlled double-blinded trial of Interleukin 1 blockade in Acute Severe Colitis: the IASO trial. BMJ Open 9, e023765 (2019).
2.Raine, T. et al. OP33 Results of a randomised controlled trial to evaluate Interleukin 1 blockade with anakinra in patients with acute severe ulcerative colitis (IASO). J. Crohns Colitis 17, i43–i46 (2023).