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Patients With RA at Greater Risk for Glucocorticoid-related Adverse Effects
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Patients with rheumatoid arthritis have a substantially greater risk for glucocorticoid-related adverse effects compared with their healthy peers, and increasing cumulative and average daily doses were associated with an increased risk for adverse effects, according to findings published in Arthritis Care & Research.
“Oral glucocorticoids — primarily prednisolone and prednisone — play an important role in routine management of RA, alongside conventional synthetic disease-modifying antirheumatic drugs and more recent biologic therapies,” Jessica C. Wilson, PhD, MSc, of the University of Basel in Switzerland, and colleagues wrote. “Their temporary use is recommended to control episodes of increased disease activity. However, [glucocorticoid] use is controversial as it is associated with an increased risk of serious adverse events, particularly in patients exposed to high doses and extended use.”
To analyze the incidence of glucocorticoid-related adverse effects — including diabetes, osteoporosis, fractures, glaucoma, hypertension, death and others — among patients with and without RA, and to quantify risk among those with RA, the researchers studied participants identified in the U.K. Clinical Practice Research Datalink. According to Wilson and colleagues, the database contains anonymous health care information for more than 10 million patients in the United Kingdom. They matched 34,050 patients with a first-time diagnosis of RA to an equal number of individuals without RA.
The researchers estimated incidence rates and incidence rate ratios for various glucocorticoid-related adverse effects — which also included gastrointestinal perforation or bleeding and thrombotic stroke or myocardial infarction — stratified by use of the drug. In addition, Wilson and colleagues completed a series of nested case-control analyses in patients with RA. In these, they studied the effects of increased both cumulative and average daily doses of glucocorticoids. Incidents of each outcome were matched to healthy controls on age, sex and general practice.
According to the researchers, patients with RA, compared with their healthy peers, demonstrated a higher incidence for all included adverse effects except for glaucoma. In addition, incidence risk ratios were greater among those prescribed a glucocorticoid than in those who were not. Among the patients with RA, glucocorticoid use was associated with an increased risk for diabetes (OR = 1.33; 95% CI, 1.141.56), osteoporosis (OR = 1.41; 95% CI, 1.251.59), thrombotic stroke or myocardial infarction (OR = 1.28; 95% CI, 1.071.52), serious infection (OR = 1.28; 95% CI, 1.111.48) and death (OR = 1.33; 95% CI, 1.191.48).
The researchers also reported an elevated risk for adverse effects associated with increasing cumulative and average daily doses of the drug (P < .05) for all outcomes except glaucoma, hypertension and gastrointestinal perforations or bleeding.
“The findings of this large observational study suggest that patients with RA are at a substantially increased incidence of [glucocorticoid]-related adverse effects,” Wilson and colleagues wrote. “These findings highlight the clinical burden associated with current and long -term, high-dose oral glucocorticoid use in patients with RA. Clinical awareness of oral glucocorticoid safety in this patient group is important for improving patient care.” – by Jason Laday
Disclosure: Wilson reports study funding from F. Hoffmann-La Roche and Genentech. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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Amanda Mixon, PA-C
Glucocorticoids are commonly used in rheumatology for many purposes and can be lifesaving in certain instances. We often use steroids in the initial treatment of rheumatoid arthritis to aid patients manage flare-ups, while some patients require steroids more chronically; however, we are aware of the risks associated with chronic steroid use and try to mitigate those risks whenever possible.
This study looked at the incidence of glucocorticoid-related adverse events in RA and non-RA patients and found that patients with RA had a higher incidence of all investigated serious adverse events except glaucoma when compared to patients without RA. At higher doses, the risk increases. It is postulated that part of this increased risk is also associated with the disease itself as patients treated with higher doses of steroids also tend to have higher disease activity.
This study does solidify that we need to be cautious with our use of steroids among RA patients and understand these patients are at a higher risk for serious adverse events. I think the study also reminds us that we need to screen our RA patients for other comorbidities, such as diabetes and heart disease, and ensure that these conditions are being addressed appropriately with their primary care provider.
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