A poster presentation at the 2024 Congress of European Crohn’s and Colitis Organization (ECCO) has highlighted the magnitude and impact of steroid overuse on inflammatory bowel disease (IBD) patients. Reporting on data from the Determinants, Incidence and Consequences of Corticosteroid Excess in IBD (DICE),^[1] the study demonstrated that steroids are still widely used – and increasing in use – in the treatment of IBD, particularly in patients with moderate to severely active disease. This is despite an increase in the availability of steroid-sparing therapies such as biologics.

The DICE study was conducted through 2021, with adult patients (age ≥18 years and >1 year post IBD diagnosis) completing an anonymous, online questionnaire about their steroid treatment in the previous 12 months. The study sought to quantify both steroid exposure and excessive use. Excessive use is often linked to steroid resistance and dependence, and is defined by the British Society of Gastroenterology (BSG) as meeting at least one of the following four criteria^[2]:

• More than one course of steroids within the last 12 months
• Glucocorticoid use for more than three months within the last 12 months
• The inability to reduce glucocorticoids below the equivalent of 10 mg/day prednisolone (or 3 mg/day budesonide) within three months of starting steroids without recurrent active disease
• Relapse within three months of glucocorticoid discontinuation

The paper presented at ECCO reported on a Spanish cohort of 253 patients. Most of the patients presented with dormant (64.4%, n=163) or mild (21.74%, n=55) disease activity, rather than moderate (11.5%, n=29) or severe disease activity (2.37%, n=6). Nearly 18% (n=45) of patients received at least one cycle of oral steroids with the highest rates of exposure (65.7%, n=23) in patients with moderate to severe activity. About half (45%) of the moderate-severe group were treated for more than three consecutive months, with one patient on steroids for 13 months. A similar picture was seen for steroid dependency; defined as patients who had received one or more courses of glucocorticoids or could not taper glucocorticoids within three months of steroid initiation. Of the 31% of steroid-dependent patients, 85.7% (n=12) had moderate to severe disease. 

The French DICE cohort (n=543) reported slightly higher levels of overall steroid exposure (24.3%, n=130) but much lower levels of steroid dependency/excessive use of steroids at 14.6% (n=78). The likelihood of requiring glucocorticoids at all was associated with the number of previous biologics received in Crohn’s disease and with current use of 5-ASA in ulcerative colitis patients.^[3] Without a comparative analysis across all cohorts, it’s difficult to know what could be driving the difference.

Overall, results from the DICE study suggest that despite significant progress in the development of new therapies, and the increasing use of biologics in IBD, glucocorticoids are still widely and frequently used to treat patients with moderate to severely active disease. Steroid exposure and excessive use are common features of IBD treatment across Europe and the risk/benefit of steroids remains a widely debated topic in the IBD community, as it does for other chronic inflammatory diseases such as rheumatoid arthritis.^[4]

Continued and increasing use of steroids linked to escalating burden of side effects for IBD patients

The impact on patients, in terms of side effects caused by glucocorticoids in IBD, was assessed in a paper from the related DICE Impact study, presented at ECCO in 2021.^[4] The study examined the FDA Adverse Event Reporting System (FAERS) for adverse events reports associated with the use of prednisone/prednisolone or budesonide in IBD patients. The study queried reports from Q1 2008 to Q4 2019, to determine the frequency of adverse events associated with steroid use. 

A total of 420,913 all-cause adverse events were reported for prednisone/prednisolone and 33,215 for budesonide, with adverse event reports for steroids increasing steadily over time for both Crohn’s disease and ulcerative colitis. Compared to other drugs based on PRR, adverse events were more likely to be reported with steroids. These included cushingoid complications (PRR 9.3) and adrenal insufficiency (PRR 3.7), which were the most common adverse events for both drugs, followed by pancreatitis (PRR 2.8 with budesonide) and osteonecrosis (PRR 2.4 with prednisone/prednisolone). Both drugs had similar levels of osteoporosis side effects (PRR 1.1-1.7). The authors reported no confounding effect from gender or disease type identified on reported adverse events. The structure of the FAERS system, however, is acknowledged to lead to substantial underestimation of the incidence of adverse events because it requires the proactive initiation of reports by clinicians. Given that all of the side effects reported are known to be associated with steroid use, it is likely that these figures represent substantial underestimates. 

Despite increasing access to new therapies to treat IBD, these publications tell a story of continued clinical reliance on steroids to control IBD disease activity, particularly in patients with moderate to severe disease activity. While the time periods of these studies aren’t in sync, the increase in steroid-related side effects over time in the DICE Impact study is consistent with the pattern of steroid use in the French and Spanish DICE cohorts, and reflects the growth in steroid prescribing patterns over time for IBD.^[4] 

Overall, the results emphasize the need to monitor and measure both steroid use and the associated side effects in patients as well as the importance of minimizing the duration and dose of steroid use through the use of steroid-sparing regimens and other strategies.  

References

1. Gomollon Garcia F,  Vega Villaamil P, Romero Cara P, et. al. Steroid use in a high proportion of IBD patients – first results from the Spanish cohort of the IBD-DICE study.  JCC 18: Issue Supplement_1: i1177 (2024) 2024:i117. https://doi.org/10.1093/ecco-jcc/jjad212.0738
2. 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 vol 68, Suppl. S3:s1–s106. https://doi.org/10.1136/gutjnl-2019-318484.
3. Nancey s, Hebuterne X, Gilletta C et. al. Prevalence of oral corticosteroid exposure and excessive use in patients with inflammatory bowel disease: data from four French referral centers of the international DICE study. J Clin Med. Vol 13(9):2652-2659 (2024)   https://doi.org/10.3390/jcm13092652
4. Raine T, Bokemeyer B, Finney-Hayward T, et. al. P468 Analysis of international spontaneous reporting system databases for safety of corticosteroids in Inflammatory Bowel Disease: The Determinants, Incidence and consequences of Corticosteroid Excess (DICE)-impact study.  JCC vol 15, Issue Supplement_1: S458-S459 (2021) https://doi.org/10.1093/ecco-jcc/jjab076.591