Though still used, glucocorticoid treatments ‘should be avoided’ in patients with RA
Click Here to Manage Email Alerts
Glucocorticoids are still one of the most commonly used treatments for rheumatoid arthritis, with an estimated up to 50% of patients with RA in the United States using them long-term as of 2021.
However, the clinical consensus has started to turn against glucocorticoid programs for patients with RA. Joan Bathon, MD, director of the division of rheumatology at Columbia University Irving Medical Center and New York Presbyterian Hospital, told Healio that while glucocorticoids may have short-term uses, the risks outweigh the potential benefits when considering their long-term use.
“Steroids should be avoided in RA patients since there are many alternatives to controlling disease activity – ie, conventional synthetic [disease-modifying antirheumatic drugs] DMARDs and targeted DMARDs,” Bathon said. “However, they occasionally may be needed in low dose for short periods of time. Among the rheumatic diseases, moderate to high dose steroids are reserved primarily for life- or organ-threatening illnesses — for example, renal injury due to systemic lupus or vasculitis.”
Research links glucocorticoids to significant side effects, including higher risk of cardiac events and risk for vertebral fractures, causing doctors to re-evaluate long-held opinions about just how worthwhile it is to put patients with RA on glucocorticoid programs.
Changing times
Glucocorticoids became a staple of RA treatment due to their efficacy; the class of steroids is among the most potent anti-inflammatories on the market. They are particularly potent in treating sharp flareups of rheumatic pain and, according to Bathon, historically achieved noteworthy results in a short period of time.
“High-dose glucocorticoids (eg, 1 g of methylprednisolone intravenously for 3 days in a row) were used occasionally in past decades for severe flares of, or persistently uncontrolled, RA with the hopes of achieving a dramatic and rapid response,” Bathon said. “However, this is rarely required in the modern era, again due to the variety and effectiveness of modern DMARDs at our disposal, some of which have more rapid onset of action than others.”
Since the start of the 21st century, numerous DMARDs effective against RA have been approved for use, including tumor necrosis factor, interleukin-6 and janus kinase inhibitors, among others. Their efficacy and relatively low risk caused glucocorticoid use to be reexamined.
Prednisone, a glucocorticoid, has been one of the most commonly prescribed medications for RA since it was introduced in the 1950s, and is still one of the most prescribed medications in the United States. However, continued scholarship on its effects has not proven kind.
“Because data suggest that even 5 mg of prednisone over long periods of time raises infection risk and cardiovascular risk, the American College of Rheumatology’s recent guidelines for the treatment of RA discourage use of steroids at all,” Bathon said. “In patients in whom a single joint is particularly inflamed, a local (intraarticular) injection may achieve therapeutic benefit in that joint while minimizing systemic glucocorticoid effects. Repository corticotropin injections are also approved for rheumatological diseases such as RA, but their long-term efficacy and toxicity have not been systematically studied in RA and are not generally endorsed. Thus, current wisdom is to avoid steroids if at all possible but, if their use is deemed necessary, use of the smallest dose possible for the shortest time possible is recommended.”
In June 2021, the American College of Rheumatology issued updated treatment guidelines, recommending use of conventional synthetic DMARDs rather than long-term glucocorticoids.
Strong side effects
Numerous studies over the past 5 years have provided new data on the risk of side effects from glucocorticoid use. These include a study that showed a 15% higher risk of cardiovascular events, one that indicated a 59% higher risk of clinical vertebral fractures and a study showing overall higher mortality rates in RA and comorbid diabetes.
According to Bathon, that isn’t all — and the risk extends even to low dosages of steroids.
“Large doses of steroids over a prolonged period of time (more than a month) may cause weight gain and Cushing’s syndrome, elevation of blood pressure, elevation of blood glucose, infection, myopathy, cataracts, and depressive or manic or even psychotic like symptoms,” Bathon said. “Fortunately, most RA patients don’t require these high doses as there is a panoply of other effective therapies at our disposal. However, even lower doses of steroids (< 10 mg of prednisone or equivalent daily), that on the surface may seem more benign, may still lead over years of use to toxicities including osteoporosis with fractures, increased risk of infection and increased risk of cardiovascular events.”
Bathon said that developing a safe equivalent moving forward will depend on being able to separate the drugs’ positive and negative effects, and while there is progress in that direction, a solution is still years away.
“Glucocorticoids have profound suppressive effects on multiple inflammatory pathways, but have equally profound adverse side effects,” Bathon said. “Dissociating these two pathways is key to the development of a novel safe glucocorticoid equivalent. Efforts are underway to develop selective glucocorticoid receptor modulators (SGRM) that favor suppression of proinflammatory modulators (such as nuclear factor kB and AP-1) over activation of genes that influence metabolic responses (such as hyperglycemia, adipogenesis and muscle wasting). However, these are still far from clinical development.”
COVID-19 concerns
Meanwhile, the continuing COVID-19 pandemic — which recently has hit another wave of infections — provides another potential risk for patients with RA using glucocorticoids.
“Regarding COVID, there is concern that glucocorticoid use may not only make patients more susceptible to COVID infection by impairing natural antibody responses, but may also impair their ability to mount an antibody response to COVID vaccines,” Bathon said. “Although there are not good studies on exact doses, doses of 20 mg or higher have been suggested as those that will impair autoantibody responses.”
An Italian study published in January 2021 supported these conclusions, suggesting that use of glucocorticoids and other immunosuppressive medications carried with it a higher risk for COVID-19 infection.
Collapse
Read more about
Click Here to Manage Email Alerts