CHICAGO – Treatment of Graves’ disease with the antithyroid drug methimazole is associated with a significantly increased risk of acute pancreatitis and, although the cases are rare, this risk justifies these warnings about this potential side effect. , according to a nationally controlled study in Denmark spanning more than 20 years.

“The data are very strong and convincing, showing that the risk of pancreatitis is the same as the risk of agranulocytosis that we have been warning about and announcing for decades,” said first author Laszlo Hegedus, PhD. Doctor, president of the European Thyroid Association, told Medscape Medical News .

“So not taking this issue seriously is really arrogant,” he said after presenting his findings at the 89th Annual Meeting of the American Thyroid Association (ATA).

With six notable case reports of acute pancreatitis associated with methimazole therapy, the European Medicines Agency (EMA) issued a risk warning in January 2019, leading to a label change. products to include acute pancreatitis as a serious side effect.

However, similar action has not been taken in the United States.

As methimazole is one of the most commonly used drugs in the United States, Hegedus said, the findings underscore the need to communicate this information to patients.

“Not informing an individual about this potentially serious side effect is in my opinion not appropriate,” he said. “We do the same in Denmark, both orally and in writing.”

Mona M. Sabra, MD, who co-hosts the program, notes that these new Danish findings are considered remarkable enough to warrant additional effort into the ATA programme.

Sabra, professor of clinical medicine in the Department of Endocrinology, Department of Medicine at Memorial Sloan Kettering and Weill Cornell Medical School in New York City, told Medscape Medical News : “This is really important new information. These data were presented at the European Thyroid Association last week, and we accepted it into the program this week due to the magnitude of the results.”

Real risk of acute pancreatitis with Methimazole

To further investigate the risk in a large number of people using methimazole and the other most common antithyroid drug, propylthiouracil (PTU), Hegedus and colleagues identified 118,649 antithyroid drug users (defined as at least one prescription for either drug) at national registries in Denmark between 1995 and 2018, including 103,825 methimazole users and 14,824 PTU users.

During the same period, there were 43,580 cases of acute pancreatitis in the general population, including 226 cases (0.5%) in methimazole users and 19 cases (0.04%) in PTU users, with case-cross-sectional analysis showed an odds ratio (OR) of 1.51 (95% CI, 1.12 to 2.02) for acute pancreatitis in methimazole users and an OR of 1.16 (95% CI) , 0.46 – 2.93) for PTU users.

Comparing case-by-case with four controls, there was no increased risk of acute pancreatitis for the highest and lowest quartiles of cumulative dose for methimazole (OR, 0.98) or PTU (OR, 0.86) ).

Nor was there any association between the cumulative dose effect (low, moderate, or high) of either drug and the risk of acute pancreatitis (OR, 1.00 for both drugs).

“The use of methimazole is ongoing but PTU use appears to be associated with an increased risk of acute pancreatitis; however, we found no evidence of a cumulative dose effect of methimazole or PTU on the risk of acute pancreatitis,” said Hegedus, from the Department of Endocrinology and Metabolism at Odense University Hospital, Denmark. said.

During a discussion of the study’s findings, one audience member asked whether hyperthyroidism itself might play a role in disease risk; however, Hegedus said to Medscape Medical News

that he was unaware of any reports linking acute pancreatitis with hyperthyroidism. Furthermore, if hyperthyroidism plays a role in the disease, it is possible that the increased risk is not limited to methimazole, he said.

“However,” he admits, “the strength of the findings with PTU is weakened by the lack of data – too few people were treated with it to rule out an effect of PTU associated with an increased risk of pancreatitis.” , said Hegedus.

And Hegedus noted a previous population-based case-control study of methimazole users in Taiwan showed no significant association with acute pancreatitis (Indian J Pharmacol. 2016; 48: 192-1995).

He added that the limitations of the present study were the lack of biochemical data, including the severity of hyperthyroidism, which prevented the distinction between Graves’ disease and toxic nodular goiter.

But with strengths including large scale, long-term investigation, and validated pharmacoepidemiological methods, Hegedus calls for “verification in an independent cohort … in an effort to investigate the mechanisms underlying mechanisms.” potential behind this adverse effect.”

He concluded: “Although I hope to refute this, the EMA warning seems reasonable. The frequency of acute pancreatitis in people taking methimazole is occurring at a level similar to that reported for agranulocytosis,” he concluded.

New and rare complications that need to be checked in the US

Kepal Patel, MD, chief of endocrine surgery and associate professor of surgery, otolaryngology, and biochemistry at NYU Langone Medical Center, agrees that the new findings are remarkable.

Patel said to Medscape Medical News : “I think it’s fascinating because it’s a new and rarely described complication. Would be great to see it in the US population… I think it looks like it could be a real complication of antithyroid drugs. That’s a small number and a rare complication, but nonetheless, if it is reported and exists, it is something we should absolutely be aware of when treating patients with antithyroid drugs. “

89th ATA Annual Meeting. Summary #6. Announced November 2, 2019.

Source: Methimazole for Graves Disease Linked to Acute Pancreatitis

Link: https://www.medscape.com/viewarticle/920778#vp_1

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Translated by: Thu Vo