Corticosteroid exposure associated with hospitalization for severe pain event among patients with sickle cell disease

People with sickle cell disease (SCD) who were recently prescribed a corticosteroid – a medicine frequently used to treat asthma or inflammation – were found to be significantly more likely to be hospitalized for a severe pain event, according to a paper published today in the journal Blood. The research also found that older adults, women, and people who were not taking the drug hydroxyurea to manage their underlying SCD symptoms were the most likely to be hospitalized.

SCD is the most common inherited red blood cell disorder in the United States, affecting an estimated 100,000 people. According to the Centers for Disease Control and Prevention (CDC), SCD affects one out of every 365 Black or African American births and one out of every 16,300 Hispanic American births. Pain events, also known as vaso-occlusive episodes (VOE), are the most common complications of SCD and can result in intense pain and potentially irreversible organ damage.

Apart from case reports, researchers say this is the first study to systematically evaluate the association between corticosteroid exposure and hospitalization for VOE.

Individuals living with SCD often suffer crippling episodes of pain, which can greatly impair their quality of life. Based on our data, corticosteroids are commonly prescribed for conditions unrelated to their underlying SCD. Vaso-occlusive events and related hospitalization appear to follow corticosteroid prescription fairly quickly. This evidence suggests corticosteroids may be contributing to the events and should be avoided as much as possible in these patients."

Ondine Walter, MD, Study Author, Toulouse University Hospital in France

Notably, the median time between filling a prescription for a corticosteroid and hospitalization was just five days. Also striking was the fact that nearly half (46%) of patients with SCD had been prescribed at least one systemic corticosteroid during the study period. Dr. Walter said the results underscore the need for widespread education of clinicians and patients alike about the potential risks of using corticosteroids, especially when there isn't a clear indication to use them.

"Corticosteroids are mostly easy to avoid, and in circumstances when they are necessary, it's important to start them in collaboration with an SCD expert and to take all appropriate precautionary measures to administer them safely," said Dr. Walter.

The study used data from a total of 5,151 patients with SCD drawn from the French National Health Insurance Database between 2010 and 2018. Patients had to have at least one hospitalization for VOE to be included, and corticosteroid exposure was identified using outpatient prescribing records.

The study found that those who had exposure to a corticosteroid – defined in the month leading up to the event – were significantly more likely to be hospitalized for VOE. People who were also taking hydroxyurea seem to have less risk of hospitalization compared with those not taking the drug, which may signal a potential protective effect of hydroxyurea on the occurrence of VOE, Dr. Walter explained. Hydroxyurea is often prescribed to reduce the number of pain events caused by SCD as well as the need for blood transfusions. The risk of admission was also lower in men compared to women and in children compared to adults.

"Some factors such as hydroxyurea use, male gender, and younger age were associated with a lower risk of hospitalization for VOE after corticosteroid exposure in our study. Still, based on these results, we still need to think twice about using corticosteroids when treating patients with SCD," said Dr. Walter.

This study is limited in that it can only show an association between corticosteroids and VOE-related hospitalizations and not prove causation. Because corticosteroid exposure was based on dispensing data, it is also not possible to confirm that patients took the medicine, only that the prescription was filled.

With future research, investigators aim to understand how corticosteroids may prompt VOE. Studies have shown that the cessation of corticosteroids, in particular, has been associated with rebound pain. ASH's Clinical Practice Guidelines on SCD recommend against using corticosteroids for acute pain management in patients with SCD. This study adds important data about the association of corticosteroid use with subsequent VOE to a growing body of evidence that suggests corticosteroids should be used only when needed, and under the guidance of an SCD expert.