Medication Failure: An Overlooked Risk Associated With 5-ASA Therapy in IBD

Medication failure is arguably the most important risk associated with 5-aminosalicylate (ASA) therapy in patients with inflammatory bowel disease (IBD), said Meenakshi Bewtra, MD, MPH, PhD, during the 2019 Advances in Inflammatory Bowel Diseases (AIBD) Meeting.¹

Dr Bewtra, who is an assistant professor of medicine at the Hospital of the University of Pennsylvania, Philadelphia, focused her presentation on the risks associated with the 5-ASA therapy mesalamine.

While patients who receive mesalamine often fail treatment, this risk is often overlooked compared with other more well-known risks associated with 5-ASA therapy. “This is because of differences in the way we view risk,” she said. Epidemiologists view risk as a measured property of a group of people, while patients or physicians view risk as an individually measured property.

“It is important we discuss mesalamine in the setting of newer drugs, because it is not risk-free, but we tend to view it that way because we often fear the newer drugs and are more comfortable using mesalamine,” she said.

Dr Bewtra also discussed the hypersensitivity complications of 5-ASA therapy: myocarditis/pericarditis, eosinophilic pneumonia, and nephritis. Myocarditis/pericarditis is often one of the earliest signs of hypersensitivity to 5-ASA therapy, and the mechanism is unclear.

“There is no single lab, sign, or symptom that is pathognomonic for myocarditis/pericarditis hypersensitivity to 5-ASA therapy,” Dr Bewtra said. Rarer complications of myocarditis include heart block, arrhythmia, and cardiac arrest, but most patients make a complete recovery with simply stopping the 5-ASA therapy. 

Eosinophilic pneumonia is an exceedingly rare, earlier complication related to 5-ASA therapy. However, some patients experience chronic eosinophilic pneumonia, which can occur up to 4 months after the start of therapy. “Treatment, like myocarditis, is stopping the 5-ASA therapy, and in this case, you want to use steroids,” she said, adding that there is an almost universal cure rate.

Renal toxicity is one of the most well-recognized complications of 5-ASA therapy; however, the real association is not clear. There are numerous case reports of renal toxicity, but increasingly larger studies are questioning whether there is a true association between the drug and the renal toxicity, Dr Bewtra explained.

For example, the United Kingdom’s adverse events monitoring system reported an extremely low rate of interstitial nephritis associated with 5-ASA therapy—about 11 cases per 1 million prescriptions. In an analysis of the UK’s General Practice Research Database, researchers looked at nearly 38,00 patients with IBD and found that those who had a prescription for 5-ASA therapy were not more likely to develop renal toxicity than those with IBD who did not have a prescription for 5-ASA therapy. “They further found there was no relationship between the type of 5-ASA therapy or the dose of the 5-ASA therapy,” she said.

A new retrospective study by Vajravelu, et al,² found that IBD is associated with an increased risk of chronic kidney disease (CKD). Dr Bewtra said that conventional teaching has emphasized the need to monitor the kidney function in any patients with IBD who receive treatment with 5-ASA therapy. “While most cases of nephrol toxicity occur in the first year, it has been reported at any time course of using 5-ASA therapy," she said. “While there are no established monitoring guidelines, it has always seemed reasonable to be checking kidney function at least annually in our patients.”

However, Dr Bewtra noted an interesting finding from the study that common IBD medications—including 5-ASA therapies—were not associated with a decreased glomerular filtration rate compared with patients not using medications, raising the possibility that the IBD itself is causing the renal toxicity. She emphasized that clinicians should be monitoring kidney function in all IBD patients, regardless of whether they are on 5-ASA therapy, and especially in the younger IBD patients.

Dr Bewtra concluded that it is important that clinicians do not underestimate the complications related to 5-ASA therapy. “While the absolute risks of these complications are rare, the absolute risk of mesalamine failure is not,” she said. “We as providers need to remember this, monitor patients, look for the treat-to-target guidelines, and not be afraid to escalate to one of the newer therapies.”

—Melinda Stevens

References:

1. Bewtra M. Don’t forget that 5-ASAs also have side effects: recognizing complications. Presented at: 2019 AIBD Meeting; December 12-14, 2019; Orlando, FL.
2. Vajravelu RK, Copelovitch L, Osterman MT, et al. Risk for chronic kidney disease in patients with inflammatory bowel diseases increases with age but is not associated with 5-aminosalicylate use. Clin Gastroenterol Hepatol. 2019;S1542-3565(19):31245-5. doi:10.1016/j.cgh.2019.10.043.