Predictors of steroid dependence and resistance in patients with ulcerative colitis

AIM: detection of steroid dependence and steroid resistance predictors in patients with ulcerative colitis (UC).

PATIENTS AND METHODS: a retrospective study was conducted. The medical documentation of 1105 patients, who underwent inpatient treatment in Ryzhikh National Medical Research Center of Coloproctology from 2018 to 2021, were analyzed. 69% of patients (n=762) received systemic steroid therapy for UC. In accordance with inclusion and non-inclusion criteria, the medical documentation of 170 patients was selected for statistical analysis. Depending on the steroid status of patients, three groups were identified: group 1 (n=56) with steroid dependence, group 2 (n=56) with steroid resistance and group 3 - control (n=58), who were prescribed systemic GCS without the further development of steroid dependence and resistance.

RESULTS: the incidence of steroid dependence was 23.4% (n=259), and steroid resistance was 15.2% (n=168). We identified the following predictors and risk factors of steroid dependence: age of the disease onset <30 y.o. (AOR=0,960, 95%CI= 0,928-0,993, p=0,019), start dose of prednisolone <60 mg (AOR=2,369, 95%ДИ= 1,030-5,441, p=0,042), prescription of systemic GCS ≥2 courses per year (AOR=2,988, 95%ДИ= 1,349-6,619, p=0,007), Mayo Index Score <10 (AOR=0,631, 95%ДИ=0,492-0,809, p<0,001). The risk of steroid resistance statistically significant when Mayo Index Score ≥10 (AOR=2,573, 95%ДИ=1,094-6,050, p=0,030), albumin level <37,1 g/l (AOR=4,571, 95%ДИ=1,567-13,330, p=0,005), CRP ≥47,1 mg/l (AOR=2,641, 95%ДИ=1,102-6,328, p=0,029).

CONCLUSION: it is rational to predict an individual response to GCS in patients with UC. With a high risk of developing steroid dependence and steroid resistance, it is advisable to consider early appointment of biological and target therapy, avoiding represcription of GCS.

1. Truelove SC, Witts LJ. Cortisone in ulcerative сolitis; final report on a therapeutic trial. British medical journal. 1955;2(4947):1041–8. doi: 10.1136/bmj.2.4947.1041

2. Fumery M, Singh S, Dulai PS, et al. Natural History of Adult Ulcerative Colitis in Population-based Cohorts: A Systematic Review. Clinical Gastroenterology and Hepatology. 2018;16(3):343–356.e3. doi: 10.1016/j.cgh.2017.06.016

3. Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG clinical guideline: ulcerative colitis in adults. American Journal of Gastroenterology.2019;114:384–413. doi: 10.14309/ajg.0000000000000152

4. Raine T, Bonovas S, Burisch J, et al. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment. Journal of Crohn’s and Colitis. 2022;16(1):2–17. doi: 10.1093/ecco-jcc/jjab178

5. Ivashkin V.T., Sheligin Yu.A., Khalif I.L., et al. Project: Clinical guidelines for the diagnostics and treatment of ulcerative colitis. Koloproktologia. 2019;18(4):7–36. (in Russ.). doi: 10.33878/2073-7556-2019-18-4-7-36

6. Knyazev O.V., Belousova E.A., Abdulganieva D.I., et al. Real world practice of medical treatment for moderate and severe inflammatory bowel diseases in Russian Federation, Republic of Belarus and Republic of Kazakhstan: intermediate results of the INTENT study. Almanac of Clinical Medicine. 2021;49(7):443–454. (in Russ.). doi: 10.18786/2072-0505-2021-49-061

7. Khalif I.L., Nanaeva B.A., Golovenko A.O., et al. Long-term results of conservative treatment of patients with severe exacerbation of ulcerative colitis. Terapevticheskii Arhiv. 2015;87(2):34–38. (in Russ.). doi: 10.17116/terarkh201587234-38

8. Belousova E.A., Abdulganieva D.I., Alexeeva O.P., et al. Social and demographic characteristics, features of disease course and treatment options of inflammatory bowel disease in Russia: results of two multicenter studies. Almanac of Clinical Medicine. 2018;46(5):445– 463. (in Russ.). doi: 10.18786/2072-0505-2018-46-5-445-463

9. Gupta V, Mohsen W, Chapman TP, et al. Predicting Outcome in Acute Severe Colitis-Controversies in Clinical Practice in 2021. Journal of Crohn’s and Colitis. 2021;15(7):1211–1221. doi: 10.1093/ecco-jcc/jjaa265

10. Travis SP, Farrant JM, Ricketts C, et al. Predicting outcome in severe ulcerative colitis. Gut. 1996;38:905–10. doi: 10.1136/gut.38.6.905

11. Lindgren SC, Flood LM, Kilander AF, et al. Early predictors of glucocorticosteroid treatment failure in severe and moderately severe attacks of ulcerative colitis. European Journal of Gastroenterology & Hepatology. 1998;10:831–5. doi: 10.1097/00042737-199810000-00003

12. Grant RK, Jones GR, Plevris N, et al. The ACE [Albumin, CRP and Endoscopy] index in acute colitis: a simple clinical index on admission that predicts outcome in patients with acute ulcerative colitis. Inflammatory Bowel Diseases. 2021;27(4):451–457. doi: 10.1093/ibd/izaa088

13. Ho GT, Mowat C, Goddard CJ, et al. Predicting the outcome of severe ulcerative colitis: development of a novel risk score to aid early selection of patients for second-line medical therapy or surgery. Alimentary Pharmacology & Therapeutics. 2004;19:1079–87. doi: 10.1111/j.1365-2036.2004.01945.x

14. Skrzypczak-Zielinska M, Gabryel M, Marszalek D, et al. NGS study of glucocorticoid response genes in inflammatory bowel disease patients. Archives of Medical Science. 2019;17(2):417–433. doi: 10.5114/aoms.2019.84470

15. Chen Y, Cui W, Li X, et al. Interaction between commensal bacteria, immune response and the intestinal barrier in inflammatory bowel disease. Frontiers in Immunology. 2021;12:761981. doi: 10.3389/fimmu.2021.761981

16. Bolotova E.V., Yumukyan K.A., Dudnikova A.V. Modern Idea of the Mechanisms of Development and Predictors of Ulcerative Colitis Severity. Doctor.Ru. 2022;21(2):34–39. (in Russ.). doi: 10.31550/1727-2378-2022-21-2-34-39

17. Koynova I.A., Beloborodova E.V., Burkovskaya V.A., et al. Features of clinical course of inflammatory bowel disease in connection with external and internal environment factors. Practical medicine. 2020;18(4):75–81. (in Russ.). doi: 10.32000/2072-1757-2020-4-75-81

18. Haritonov A.G., Shcukina O.B., Kondrashina E.A. Steroid resistance in inflammatory bowel disease. Almanac of Clinical Medicine. 2016;44(6):734–743. (in Russ.). doi: 10.18786/2072-0505-2016-44-6-734-743

19. Alekseeva O.P., Krishtopenko S.V., Alekseeva A.A. Using DoseEffect Relationship for Optimising Systemic Corticosteroid Dosage in Treatment of Inflammatory Bowel Diseases. Russian Journal ofGastroenterology, Hepatology, Coloproctology. 2020;30(5):18–25. (in Russ.). doi: 10.22416/1382-4376-2020-30-5-18-25

20. Reinisch W, Reinink AR, Higgins PD. Factors Associated With Poor Outcomes in Adults With Newly Diagnosed Ulcerative Colitis. Clinical Gastroenterology and Hepatology. 2015 Apr;13(4):635–42. doi: 10.1016/j.cgh.2014.03.037

21. Feuerstein JD, Isaacs KL, Schneider Y, et al; AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis. Gastroenterology. 2020 Apr;158(5):1450–61. doi: 10.1053/j.gastro.2020.01.006

22. Dias CC, Rodrigues PP, da CostaPereira A, et al. Clinical predictors of colectomy in patients with ulcerative colitis: systematic review and meta-analysis of cohort studies. Journal of Crohn’s and Colitis. 2015 Feb;9(2):156–63. doi: 10.1093/ecco-jcc/jju016

23. Abdulganieva D.I., Bakulev A.L., Belousova E.A., et al. Early prescription of biological agents for immune-mediated inflammatory diseases: opportunities and prospects. An expert’s opinion. Modern Rheumatology Journal. 2020;14(3):7–18. (in Russ.). doi: 10.14412/1996-7012-2020-3-7-18

24. Achkasov S.I., Shapina M.V., Veselov V.V., et al. Predictors of colectomy in patients with «extremely severe» ulcerative colitis. Koloproktologia. 2020;19(3):37–48. (in Russ.). doi: 10.33878/2073-7556-2020-19-3-37-48