Methimazole Treatment and Risk of Acute Pancreatitis: A Population-based Cohort Study

Abstract

Context A warning has been recently issued by the European Medicine Agency (EMA) regarding a potential increased risk of acute pancreatitis (AP) in methimazole (MMI) users. Objective To investigate the association between MMI and diagnosis of AP in a population-based study. Materials and methods A retrospective analysis of administrative health databases was conducted (2013-2018). Relevant data were obtained from: i) inhabitants registry, ii) hospital discharge records (ICD-9-CM 577.0), iii) drug claims registry (ATC H03BB02). We evaluated AP risk in MMI users in 18 months of treatment, stratifying results by trimester. Poisson regression was used to estimate the age- and sex-adjusted Rate Ratios (RR), and the relative 95% confidence intervals (CI), comparing rates of AP between MMI users and non-users. The absolute risk of AP in MMI users was also calculated. Results A total of 23,087 new users of MMI were identified. Among them, 61 hospitalizations occurred during the study period. An increase in AP risk was evident during the first three trimesters of therapy (RR 3.40 [95%CI 2.12-5.48]; RR 2.40 [95%CI 1.36-4.23]; RR 2.80 [95%CI 1.66-4.73]), but disappeared thereafter. The AP absolute risk in MMI users during the first 18 months of treatment was less than 0.4% in all sex- and age-classes. Conclusions Our results support the EMA warning, suggesting an increased risk of AP associated with MMI use. However, such an increase seems limited to the first months of MMI treatment. Moreover, in absolute terms, the probability of AP is low among patients, well below 1%.

Hyperthyroidism

“…In Europe, pancreatitis was recently added as an adverse effect of methimazole, although data for this are conflicting. The absolute risk over the initial 18 months of therapy appears to be less than 0.4% …”

“…Treatment should be patient centered and individualized, taking into account age, comorbidities, severity of hyperthyroidism, likelihood of remission, plans for pregnancy, available surgical expertise, and patient preferences (Table 3). Treatment choices should be informed by the underlying etiology. In patients with Graves disease, treatment should focus on controlling hyperthyroidism with anticipated eventual remission of Graves disease, whereas causes of hyperthyroidism due to toxic nodular disease require indefinite treatment if antithyroid drugs are used because this does not remit (Figure 2).…”

Risk of Severe Infection among Rheumatoid Arthritis Patients on Biological DMARDs: A Population-Based Cohort Study

“…); (2) hospital information system, including hospital discharge records from public or private hospitals; (3) co-payment exemption registry; (4) and drug claims registries, including records of the drug prescriptions reimbursable by the Italian National Health Service dispensed by hospital and local pharmacies. These databases can be linked through a unique encrypted identifier and have largely been used for epidemiological research [ 10 , 11 , 12 ]. All procedures conducted in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments.…”

Autoimmune conditions and pancreatic cancer risk in older American adults

“…Ankylosing spondylitis has been significantly associated with cancer risk of the ampulla of Vater, 14 which connects pancreatic ducts to the small intestine. Methimazole, an antithyroid medication used to treat Graves' disease, has been shown to increase the risk of acute pancreatitis and might contribute to the association we observe 30 . To the best of our knowledge, no previous study has examined the association of ulcerative colitis with PNETs.…”

“…Methimazole, an antithyroid medication used to treat Graves' disease, has been shown to increase the risk of acute pancreatitis and might contribute to the association we observe. 30 To the best of our knowledge, no previous study has examined the association of ulcerative colitis with PNETs. One population-based study based on the Dutch Pathology Registry reported a higher prevalence of colonic neuroendocrine tumors among inflammatory bowel disease patients compared to the general population.…”