P0599 Efficacy and safety of intravenous methylprednisolone and hydrocortisone in Acute Severe Ulcerative Colitis (ASUC) – a posthoc analysis of the IASO trial
Authors: Thakor A , Drobne D , Vaja S , Subramanian S , Qian W , Davis-Wilkie C , Parkes M , Kaser A , Raine T 
Published: January 2025

Abstract

Background
Intravenous corticosteroids remain the cornerstone of initial management of ASUC. Methylprednisolone and hydrocortisone are two commonly used intravenous (IV) steroids recommended in guidelines.1 Methylprednisolone has less frequent dosing requirements and is reported to have weaker mineralocorticoid effects compared to hydrocortisone, theoretically reducing the risk of hypokalaemia.2 Comparative data on the efficacy and safety of the two drugs in ASUC are lacking.
In the IASO trial patients with ASUC were randomised to receive IV corticosteroids according to local practice, alongside either placebo or anakinra. There were no differences in the efficacy and safety outcomes for groups treated with placebo or anakinra. In this posthoc analysis we examine efficacy and safety outcomes for patients treated with IV methylprednisolone and hydrocortisone.

Methods
Data from anakinra and placebo treated groups were pooled and efficacy compared according to choice of IV corticosteroid, using logistic regression to control for potential confounders (sex, new diagnosis UC, previous ASUC, baseline albumin and baseline CRP).
Adverse events were assigning into one of four subgroups and then Fisher’s exact test was used to assess the significance of any difference in hypokalaemia incidence.
Due to posthoc nature of this analysis, p values are considered nominal.

Results
Unadjusted need for rescue therapy by day 10 was 17/39 (44%) for methylprednisolone and 21/67 (31%) for hydrocortisone respectively, with no significant difference between groups (p=0.205).
Unadjusted need for colectomy by day 98, was 6/38 (16%) for methylprednisolone and 3/67 (4%) for hydrocortisone respectively with no significant difference between the groups (p=0.047).
Logistic regression identified baseline albumin as a significant predictor in the need for rescue therapy by day 10, but not the type of corticosteroid. None of the predictors were significant for day 98 colectomy, including type of corticosteroid.
Safety profiles were broadly comparable, although rate of hypokalaemia was 0/19 (0%) in the methylprednisolone group and 6/58 (10%) in the hydrocortisone group (p=0.33).

Conclusion
This posthoc analysis showed similar rates of rescue therapy in patients treated with IV methylprednisolone and IV hydrocortisone in the initial management of ASUC.
Safety profiles were similar, although the incidence of hypokalaemia appeared higher in the hydrocortisone group. These results suggest that IV methylprednisolone is an appropriate choice for treatment of ASUC with efficacy and safety at least comparable to hydrocortisone and favourable dosing frequency.

References
1.Lamb CA, Kennedy NA, Raine T, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut 2019;68:s1-s106.
2.Wiles A , Bredin F , Chukualim B , et al. In the treatment of flares of inflammatory bowel disease, intravenous hydrocortisone causes greater falls in blood potassium and more severe episodes of hypokalaemia than methylprednisolone. Gut 2011;60(Suppl 1):A223–4.doi:10.1136/gut.2011.239301.471