Glucocorticosteroid Use for Rheumatoid Arthritis Increases CVD, Infection Mortality Risk Even After Cessation

Glucocorticosteroids (GCs) increase cardiovascular disease (CVD) and infection mortality risk in people with rheumatoid arthritis (RA) even after cessation, according to a new study.¹

Data from a longitudinal study of a population-based incident RA cohort were presented at the American College of Rheumatology (ACR) Convergence 2024, held November 15-19 in Washington, DC, by Diane Lacaille, MDCM, MHSc, Scientific Director and Senior Scientist at Arthritis Research Canada and Professor, Department of Medicine, University of British Columbia, Vancouver.

“We’ve known for decades that steroid risks are dose-dependent, especially when you get above 7.5 to 10 mg of prednisone per day,” Beth Wallace, MD, assistant professor. University of Michigan and VA Ann Arbor Healthcare Center, said in a statement.² “The open question is whether the risks of steroid use in this range, especially long-term use, outweigh the benefits. This is hard to answer because a lot of the scarier steroid side effects take years to show up. We do have clinical trial data to show that long-term use of even low-dose steroids substantially increases the risk of infections. And we have lots of observational data suggesting that even short-term steroid use increases serious risks at a population level – things like sepsis, GI bleeding, cardiovascular morbidity.”

Wallace is giving a related talk during the meeting focused on systemic steroid use, its associated risks and benefits, and role in treatment regimens for rheumatic diseases.

The cohort included all incident RA cases in British Columbia, Canada, who met RA definition between January 1996 and December 2013, using a 5 yr look back period, who were followed until the end of 2018.

Lacaille analyzed data from 28,078 incident GC users (55.9% of cohort), who had a mean GC use duration of 603 days (standard deviation [SD], 1116) and median of 131 days (IQR, 580). There were 2,489 CVD deaths and 387 from infections during follow-up. According to Cox proportional-hazards models, the risk of mortality due to CVD or infection increased by 7.5% and 6.8%, respectively, for every year of GC use and decreased by 1.3% and 4.9%, respectively, for every year after stopping GC. Both variables had non-linear relationships with mortality.¹

“I think it makes sense to frame conversations around steroid use in terms of a stewardship model, in the same way we do for antibiotic and opioid use. Thinking about ‘steroid stewardship’— that is, in terms of risks and benefits rather than absolutes – can help providers justify using steroids when there is a net benefit and avoid using them when there is net harm,” Wallace said.²

The investigators found that in people who used GC for over 2 years and 3 years had elevated risks of CVD and infection-related mortality, respectively, that never returned to pre-GC use levels. In people who used GC for 6, 12, and 24 months, it took 1.5, 3.5 and 10 years after cessation for risk of CVD mortality to decrease to that of someone prior to starting GC. Similarly, it took 2.5, 3.5, and 5.5 years, respectively, after cessation for risk of deaths from infection to decrease accordingly.¹

“They have risks and benefits, and those risks and benefits aren’t the same for every disease or every person. It’s important to have clear, ongoing conversations about steroids and to recognize that these risks include withdrawal symptoms when long-term steroids are tapered,” Wallace said.²

REFERENCES
1. Lacaille D, Danieli C, Moolooghy K, Abrahamowicz M. Changes in Mortality Risk After Stopping Glucocorticosteroids – a Population-based Study in Rheumatoid Arthritis. Presented at: ACR Convergence 2024; November 15-19; Washington, DC. Abstract 2673.

2. Corticosteroids: One Size Does Not Fit All. News release. ACR. November 14, 2024.