Analysis of the Association of Administration of various glucocorticoids with development of acute pancreatitis using US Food and Drug Administration adverse event reporting system (FAERS).

Background: There have been debates about the association between the administration of glucocorticoids and the development of acute pancreatitis, since many anecdotal cases of this adverse event were affected either by concomitant diseases (such as systemic lupus erythematosus, SLE) that may develop acute pancreatitis without glucocorticoid treatment or by co-administered drugs with high risk for the event. The aim of the present study was to explore whether disproportionally elevated signals of developing acute pancreatitis may be detected in patients receiving glucocorticoids as compared those receiving other drugs.

Methods: We retrieved spontaneously reported cases of acute pancreatitis and clinically related adverse events (target events) from the US Food and Drug Administration Adverse Event Reporting System (FAERS) using 18 preferred terms (PTs). Target drugs studied were cortisol, cortisone, prednisolone, methylprednisolone, triamcinolone, dexamethasone, and betamethasone. After cleaning the data, we calculated reporting odds ratios (RORs) and 95% confidence intervals (CIs) of acute pancreatitis in patients who received one of the glucocorticoids. RORs were calculated for each glucocorticoid using all reported cases irrespective of reporters' judgement about the contribution of the target drugs to events [i.e., primary suspected medication (PS), secondary suspected medication (SS), concomitant medication (C) and interacting (I)] and using cases with higher certainty of contribution (PS and SS), separately. When the lower limit of 95% CI of a ROR signal exceeded 1.0, the signal was considered statistically significant.

Results: The RORs (95% CIs) calculated using all reported cases (PS, SS, C, and I) for cortisol (1.68; 1.43-1.98), prednisolone (1.33; 1.19-1.47), methylprednisolone (1.77; 1.55-2.02) were significant, whereas those for other target drugs were insignificant. Using the cases in which target drugs were considered to contribute the events with higher certainty (PS or SS), RORs for prednisolone (1.31; 1.10-1.55), methylprednisolone (1.62; 1.30-2.01), and dexamethasone (1.27; 1.10-1.47) were considered significant, whereas those for others were insignificant. Regarding the performance of PTs for detecting signals (RORs) associated with acute pancreatitis from FAERS database, "pancreatitis acute" gave RORs with higher significance than others, whereas more specific PTs, "haemorrhagic necrotic pancreatitis", "ischaemic pancreatitis", "pancreatic necrosis" and "pancreatitis necrotising", gave RORs with greater magnitude.

Conclusion: The present study demonstrated that the overrepresentation of signals for acute pancreatitis may be detected for prednisolone, methylprednisolone, and some others in the FAERS database.(372 words).