P2671 - 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

Tim Raine, MD¹, Bernd Bokemeyer, MD², Tricia Finney-Hayward, PhD³, Melvin Munsaka, PhD⁴, Meng Liu, PhD⁴, Edouard Louis, MD^5
1Cambridge University Hospitals, Cambridge, England, United Kingdom; ²Gastroenterology Practice Minden, Minden, Berlin, Germany; ³AbbVie Ltd., Maidenhead, England, United Kingdom; ⁴AbbVie Inc., North Chicago, IL; ⁵CHU Liège University Hospital, Liege, Liege, Belgium

Introduction: Long-term use of corticosteroids (CS) may result in significant risk of adverse events (AEs), and the true incidence of AEs in patients with inflammatory bowel disease (IBD) receiving CS is unknown.¹ Such AE data may be reported in spontaneous reporting systems (SRS). Using data-mining algorithms for disproportionality, we determined the frequency of AEs of special interest (AESIs) associated with CS in patients with IBD.

Methods: The FDA SRS database (FAERS) was examined for AE reports associated with prednisone/prednisolone (PRED) or budesonide (BUD) use for Crohn’s disease or ulcerative colitis from Q1 2008 to Q4 2019. The incidence of key predefined AESIs was determined and the association with CS therapy was assessed using the proportional reporting ratio (PRR) criteria.

Results: Totals of 420,913 and 33,215 all-cause AEs were reported for PRED and BUD, respectively. The number of AE reports for each CS increased over time (Figure 1, a) and this was reflected in an increase in the proportion of reports of all AEs over time relating to CS. Common AEs reported with CS therapy included diarrhoea, abdominal pain, pyrexia and weight loss (Figure 1, b). Compared with other drugs and based on the PRR criteria, AESIs including osteonecrosis, adrenal insufficiency and Cushingoid complications were more frequently reported in patients treated with PRED; adrenal insufficiency, pancreatitis and Cushingoid complications were more frequently reported in patients treated with BUD (Table 1). There was no confounding effect from gender or disease type identified between CS and any of the AESIs in patients with IBD.

Discussion: Analysis of FAERS demonstrated that steroid-treated patients with IBD report AEs that are consistent with the known safety profile for CS. Cushingoid complications and adrenal insufficiency were common signals for PRED and BUD. The increased reporting of AEs over time may reflect growth in CS prescribing, or growing awareness and reporting of CS AEs by prescribers. This analysis will be repeated in multiple international SRS systems to provide a global image of AEs for CS use in IBD.


Figure: Figure 1. Total number of AE reports Q1 2008 to Q4 2019 (a) and most common AEs reported (b) by treatment and indication.

PRR (95%CI)

AESI PRED (N=7,870) vs other BUD (N=2,287) vs other drugs (N=37,438,241) drugs (N=37,823,072)

Osteonecrosis 2.4 (1.7, 3.4) 0.6 (0.1, 2.2) Hyponatraemia 0.2 (0.1, 0.3) 0 (0, NA) Diabetes 0.6 (0.4, 0.7) 0.6 (0.3, 0.9) Adrenal insufficiency 3.7 (2.7, 5.1) 4.1 (2.4, 7.1) Pancreatitis 1.8 (1.5, 2.2) 2.8 (2.1, 3.8) Cushingoid complications 9.3 (6.3, 13.6) 13.8 (7.9, 24.3) Glaucoma 0.7 (0.4, 1.4) 0.8 (0.3, 2.5) Cataract 1.1 (0.8, 1.4) 0.6 (0.3, 1.2) Osteoporosis 1.6 (1.2, 2.1) 1.7 (1.0, 2.8) Psysiatric morbidity 1.0 (0.4, 2.2) 0 (0, NA)

Table: Table 1. PRRs for key AESIs

PRR = ratio of the number of AESI reports for PRED or BUD divided by the number of AESI reports for all other drugs in each database. Bold indicates a signal of disproportionate reporting based on the PRR criteria: PRR ≥2c, the lower bound of the PRR confidence ≥1, associated X2 ≥4, and the number of events in each treatment group ≥3.
AESI, adverse event of special interest; BUD, budesonide; CI, confidence interval; PRED, prednisone/prednisolone; PRR, proportional reporting ration; NA, not applicable.


Disclosures:
Tim Raine: AbbVie – Consultant, Grant/Research Support, Speaker's Bureau. Biogen, Celgene – Consultant. Falk – Speaker's Bureau. Ferring – Consultant, Speaker's Bureau. Galapagos – Consultant. Given Imaging – Grant/Research Support. Hexal, Hospira – Consultant. Janssen – Consultant, Grant/Research Support, Speaker's Bureau. Merck – Speaker's Bureau. MSD – Consultant, Grant/Research Support. Pfizer – Consultant, Grant/Research Support. Shire – Consultant. Takeda – Consultant, Grant/Research Support, Speaker's Bureau. UCB – Grant/Research Support. Vifor – Speaker's Bureau.
Bernd Bokemeyer: AbbVie, Ferring, Janssen, Takeda – Consultant, Grant/Research Support, Speaker's Bureau. Biogen, Celgene – Consultant. Celltrion – Speaker's Bureau. Falk – Speaker's Bureau. Galapagos, Hexal, Hospira – Consultant. Given Imaging, UCB – Grant/Research Support, Speaker's Bureau. Merck, Vifor – Speaker's Bureau. MSD – Consultant, Speaker's Bureau. Pfizer – Consultant, Grant/Research Support. Shire – Consultant.
Tricia Finney-Hayward: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Melvin Munsaka: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Meng Liu: AbbVie – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).
Edouard Louis: AbbVie, Janssen, Pfizer and Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speaker's Bureau. Arena, Eli Lilly, Gilead-Galapagos – Advisory Committee/Board Member. Celgene, Ferring, MSD, Pfizer – Advisory Committee/Board Member, Speaker's Bureau.


Tim Raine, MD¹, Bernd Bokemeyer, MD², Tricia Finney-Hayward, PhD³, Melvin Munsaka, PhD⁴, Meng Liu, PhD⁴, Edouard Louis, MD⁵. P2671 - 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, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.