Now, 75 years after the first presentations were made on the “sensational” effects of cortisone in the treatment of rheumatoid arthritis (RA), glucocorticoids (GCs) are still highly relevant and widely used in the management of RA and other immune-mediated inflammatory diseases.
“It makes me smile because this is such an old drug, and we need it still so much. It still hasn’t been replaced,” Josef S. Smolen, MD, observed at annual European Congress of Rheumatology.
At low doses, GCs are highly effective as anti-inflammatory and anti-destructive agents in RA and many other diseases, said Dr. Smolen, a rheumatologist and immunologist and professor emeritus at the Medical University of Vienna, Austria.
But even after all this time, the mechanisms that lead to efficacy vs toxicity have yet to be clarified. “Such separation may provide further insights into future treatment options,” said Dr. Smolen.
Dr. Josef S. Smolen
His comments, made during a special session on the 75th anniversary of GCs at EULAR 2024, underscore the endless saga to manage GCs while finding better alternatives. Opinions differ on what the research says on toxicity and dosage and whether a long-term, low-dose option is viable. Alternative therapies are being studied, but those endeavors are still in the early stages of development.
While GCs are still used chronically in many patients, clinicians should always attempt to discontinue them whenever possible, Frank Buttgereit, MD, professor of rheumatology and deputy head of the Department of Rheumatology and Clinical Immunology at Charité – Universitätsmedizin Berlin, Germany, told attendees at the congress. Up to 60% of patients in registries use GCs, and many patients with early or established RA enter randomized controlled trials on GCs as maintenance therapy.
Sara Freeman/MDedge News
Dr. Frank Buttgereit
The ubiquity of GC usage stems in part from overprescribing by non-rheumatologist physicians who might not have access to or aren’t aware of newer biologics or disease-modifying antirheumatic drugs (DMARDs). “We see a lot of patients on long-term glucocorticoids, chronic use for years and years, decades of glucocorticoids,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Italy, who has coauthored several studies on the use of GCs.
Dr. Giovanni Adami
Societies Agree: Discontinue as Fast as Possible
GCs have been associated with a long list of adverse events, most notably Cushing syndrome, hypertension, cardiovascular disease, osteoporosis, myopathy, peptic ulcer, adrenal insufficiency (AI), infections, mood disorders, ophthalmologic disorders such as cataracts, skin disorders, menstrual septic necrosis, and pancreatitis.
Dose matters, Dr. Smolen said, citing studies that found that cumulative GC doses of 1000 or 1100 mg increase risks. One study by German researchers found that doses above 10 mg/d significantly raised the hazard ratio for death.
Because high disease activity is also associated with an equally high mortality risk, “we have to balance this out: Active disease vs glucocorticoid use, especially in countries that have less access to modern therapies than we have in the more affluent Western regions,” Dr. Smolen said.
Rheumatology societies generally agree that clinicians should try to minimize GC use or eventually discontinue the therapy.
The American College of Rheumatology recommends not using GCs as part of the first-line treatment of RA. “And if you want to use [them], you should do that for less than 3 months, taper and discontinue as fast as possible, and use the lowest dose possible,” Dr. Adami said.
EULAR’s recommendation is more nuanced in that it allows for a lower dose but gives physicians more choice in how they want to handle GCs, Dr. Adami said. The task force added that all patients should try to taper down or discontinue as fast as possible, he said.
For GCs in the management of systemic lupus erythematosus, a EULAR task force recommended that the type and severity of organ involvement should determine dose, with a long-term goal of maintaining the dose < 5 mg/d or possibly withdrawing it.
EULAR also recommends GC bridging when initiating or changing conventional synthetic (cs) DMARDs. This effectively dismisses the use of GCs when using biologic DMARDs or targeted synthetic DMARDs. As a bridging therapy, EULAR recommends either a single parenteral dose of GC or a predefined tapering or discontinuation scheme within 3 months, when starting an oral GC.