By Anne Harding
NEW YORK (Reuters Health) - 31/1/2019
Azathioprine is associated with a six-fold increased risk of acute pancreatitis in children with inflammatory bowel disease (IBD), new research shows.
"The current study expands on previous findings in adults and underlines the importance and feasibility of investigating drug safety concerns in pediatric patients," Dr. Viktor Wintzell of the Karolinska Institutet in Stockholm told Reuters Health in an email.
"Children can differ from adults in terms of disease severity, treatment patterns, and how drugs are distributed and metabolized in the body, which means that risks of adverse events can be both higher and lower in comparison with adults," he added. "This calls for more drug safety research targeted exclusively at pediatric patient groups."
Azathioprine is widely used in adults and children with IBD as a maintenance medication, Wintzell and his team note in their January 23 report in Lancet Child and Adolescent Health. Acute pancreatitis occurs in 3% to 7% of adults within months of starting azathioprine, they add, but the risk for children is not clear.
Using register-based data from Sweden for 2006-2016 and from Denmark for 2000-2016, the authors matched 3,374 pediatric IBD patients prescribed azathioprine to 3,374 pediatric IBD patients who were not prescribed the drug. During the first 90 days after starting azathioprine, 40 patients developed acute pancreatitis, compared to six patients in the non-exposed group. Incidence rates were 49.1 events per 1,000 person-years in the azathioprine group and 8.4 per 1,000 for the non-exposed group. Azathioprine was associated with a higher risk of acute pancreatitis (incidence rate ratio 5.82).
The findings underscore the importance of "regular and rigorous" monitoring for pediatric patients who start azathioprine, Wintzell and his team write. Regular visits and testing of lipase and amylase levels are adequate for early detection of acute pancreatitis, the author said.
Azathioprine is among the most widely used drugs in pediatric IBD, and it's prescribed more commonly in children with IBD than adults, he added. "Despite the risk of adverse events, including the risk of acute pancreatitis, azathioprine remains a cornerstone of the treatment strategy in pediatric IBD owing to its effectiveness."
He added: "Alternatives to azathioprine treatment include aminosalicylates, which are often used before initiation of thiopurines in mild to moderate disease, especially in ulcerative colitis. Another option is TNF inhibitors (biologics), which can be used alone or concomitantly with thiopurines in moderate to severe disease. None of the other IBD drugs (aminosalicylates, TNF-i, or corticosteroids) have known associations with the risk of pancreatitis."
The study "adds important information for the management of paediatric inflammatory bowel disease," Dr. Marina Aloi and Dr. Salvatore Cucchiara of Sapienza University of Rome write in an accompanying editorial. "In the future, the accurate definition of subgroups of patients with a high risk of specific adverse events will be key; given the growing therapeutic options available, such information will allow the most effective and safest therapy to be chosen at the right moment for each patient."