Role of pharmacoepidemiology studies in addressing pharmacovigilance questions: a case example of pancreatitis risk among ulcerative colitis patients using mesalazine

PURPOSE: Well-designed pharmacoepidemiology studies address several limitations of postmarketing spontaneous reports in regard to signal evaluation. This study evaluated a signal of disproportionate reporting of acute pancreatitis cases observed in patients with ulcerative colitis (UC) treated with MMX Multi Matrix System® (MMX®) mesalazine and demonstrated how inherent limitations of postmarketing reports were overcome. METHODS: Adults with UC who were new users of MMX mesalazine or another branded mesalazine (controlled-release, delayed-release, or extended-release mesalazine; balsalazide disodium; olsalazine sodium; sulfasalazine; or sulfasalazine delayed-release) were identified from a large US administrative healthcare claims database. Acute pancreatitis incidence rates were compared between patients on MMX mesalazine versus comparator therapies. Propensity scores were used to match patients on MMX mesalazine with patients on comparator drugs to achieve a balance of baseline patient factors. RESULTS: Crude incidence rates [95 % confidence interval (CI)] of acute pancreatitis among patients on MMX mesalazine were similar to those of patients on comparator therapies [8.55 (5.54–13.21) vs 10.05 (7.54–13.41) per 1000 person-years]; the resulting incidence rate ratio (IRR) was [0.85 (0.48–1.47)]. Propensity score-matching had little influence on the IRR [0.84 (0.46–1.55)]; nor did further adjustment by demographic characteristics, daily dose, and causes of acute pancreatitis [0.76 (0.41–1.43)]. CONCLUSION: Findings of no increase in pancreatitis risk with MMX mesalazine demonstrate the value of pharmacoepidemiology studies for evaluating a drug’s postmarket safety profile when confronted with spontaneous reporting data suggestive of a safety issue. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00228-014-1660-7) contains supplementary material, which is available to authorized users.