Abstract Background Baseline C-reactive protein (CRP) is a well-established biomarker for assessing corticosteroid response in acute severe ulcerative colitis (ASUC). With 56% of Australian inflammatory bowel disease (IBD) patients classified as overweight or obese, understanding how excess adiposity influences treatment response is critical. 1 Obesity induces chronic inflammation, elevating IL-6 and CRP production, and alters drug pharmacokinetics.2,3 Whether Body Mass Index (BMI) confounds or modifies the Risk of Rescue (RoR) score, a CRP-based tool developed at our institution, remains unknown.4 We examined: (i) the independent association of BMI/obesity with steroid failure, (ii) confounding of CRP’s prediction by BMI/obesity, and (iii) differences in the CRP-outcome relationship across weight strata. Methods All consecutive admissions meeting Truelove-Witts’s criteria for ASUC at our tertiary centre (January 2011–December 2023) were retrospectively reviewed. Demographic, clinical, endoscopic, and laboratory data, including BMI from admission measurements, were collected. Steroid failure was defined as requiring rescue medical therapy or colectomy during admission. Logistic regression assessed associations between steroid failure, baseline CRP (log10 transformed, CRP ≥12 mg/L), continuous BMI, and obesity (BMI ≥30 kg/m²). Multivariable models evaluated confounding and CRP-obesity interactions. Goodness-of-fit was assessed by Akaike information criterion (AIC), with statistical significance at p 0.05. Results Of 128 admissions (99 non-obese, 29 obese), obese patients were older (41 vs. 30 years, p = 0.020) and predominantly female (59% vs. 36%, p = 0.032). Baseline clinical characteristics, including CRP levels, were similar between groups. Steroid failure rates did not differ significantly (66% obese vs. 63% non-obese, p = 0.776). CRP significantly predicted steroid failure (p = 0.025), whereas BMI and obesity did not. BMI adjustment minimally impacted CRP predictive performance; CRP-obesity interaction was not significant (p = 0.92). Conclusion Obesity did not confound the predictive power of C-reactive protein in this cohort. Admission CRP can continue to be used in early risk stratification tools, like the RoR score, without needing adjustment for a patient’s BMI. Further research is necessary to confirm these findings and to explore if obesity impacts optimal dosing strategies for rescue therapies. References: 1. Kaazan P, Su WK, Rayner C, Walker G, Wilson W, Dinoy E, et al. The prevalence and impact of obesity in an ANZ cohort of people with inflammatory bowel disease: Crohn’s Colitis Cure (CCC) data insights program. J Gastroenterol Hepatol. 2024;39(s1):198-9. 2. Hildebrandt X, Ibrahim M, Peltzer N. Cell death and inflammation during obesity: “Know my methods, WAT(son)”. Cell Death Differ. 2023;30:279-92. doi: 10.1038/s41418-022-01062-4 3. Goleva E, Covar R, Martin RJ, Leung DY. Corticosteroid pharmacokinetic abnormalities in overweight and obese corticosteroid resistant asthmatics. J Allergy Clin Immunol Pract. 2016 Mar-Apr;4(2):357-60.e2. doi: 10.1016/j.jaip.2015.11.013. 4. Croft A, Okano S, Hartel G, Lord A, Walker G, Tambakis G, Radford-Smith G. A personalised algorithm predicting the risk of intravenous corticosteroid failure in acute ulcerative colitis. Aliment Pharmacol Ther. 2024;60(10):921-33. doi: 10.1111/apt.18190. Conflict of interest: Dr. Goetz, Naeman: No conflict of interest Okano, Satomi: No conflict of interest Hartel, Gunter: No conflict of interest Tambakis, George: No conflict of interest Phillips, Jennifer: No conflict of interest Hanigan, Katherine: No conflict of interest Brown, Alison: No conflict of interest Radford-Smith, Graham: No conflict of interest Croft, Anthony: No conflict of interest Walker, Gareth: In the last 24 months, Dr Walker has received investigator grants or served as a speaker, a consultant or an advisory board member for: Janssen AbbVie Takeda Ferring Dr Falk Pharma Georgiamune
Goetz et al. (Thu,) studied this question.