Corticosteroid Use In Rheumatoid Arthritis
Corticosteroids have a complicated role in treating RA. How are researchers working to find the balance between the benefits and risks?
Cortisone – the original corticosteroid – was considered a miracle drug when it was first used in 1949 to treat rheumatoid arthritis. Newer treatments for the disease have since come along, but corticosteroids – also commonly referred to as glucocorticoids – remain a powerful, if somewhat flawed, weapon in the anti-inflammatory arsenal, and there’s emerging evidence they do more than just provide symptomatic relief.
In fact, a study from the Netherlands, published in 2012 in the Annals of Internal Medicine, found that adding prednisone to a methotrexate regimen early in the disease process had numerous positive effects versus using methotrexate alone, including less joint damage, less physical disability and reduced disease activity.
“The correct use of [corticosteroids] will help to protect the joints from future damage and will mean that some patients will not need to go on to other treatments, such as biological agents, which are more dangerous and much more expensive,” says John R. Kirwan, MD, of the University of Bristol Academic Rheumatology Unit, Bristol, United Kingdom.
Dr. Kirwan suggests that therapy with corticosteroids – specifically, prednisone – in conjunction with another disease-modifying antirheumatic drug (DMARD), should be considered the “gold standard” for early treatment of RA. And yet, Dr. Kirwan admits some doctors avoid using corticosteroids for RA, primarily because of concern about side effects.
The Ups and Downs of Corticosteroids
Without a doubt, prednisone and other drugs in the class do come with a substantial number of possible side effects – most of which are dose-related.
“Some of the side effects include weight gain and thinning of the skin, which can lead to increased bruising,” says Stanley Cohen, MD, clinical professor of medicine at the University of Texas Southwestern Medical School in Dallas. “There’s acceleration of bone loss with higher risk of fracture, increases in blood sugar and in every clinical trial, the group of patients on prednisone always had a greater risk of infection.”
Elena M. Massarotti, MD, rheumatologist and associate professor at Harvard Medical School in Boston, calls the use of prednisone and other corticosteroids “the classic double-edged sword.”
“There’s some evidence prednisone in low doses may improve the radiographic features of rheumatoid arthritis,” Dr. Massarotti says. "The general teaching in the management of patients with rheumatoid arthritis has been to minimize corticosteroid use and preferably to eliminate it altogether.”
Dr. Massarotti says prednisone’s primary utility in RA is as a “bridge” drug – one which can provide relief for a short time while other, safer drugs are taking effect – or one which can be used if a patient experiences a flare. “So they might need a short course of corticosteroids to quiet symptoms down,” she says.
Corticosteroids reduce inflammation because they are chemically similar to the body’s natural anti-inflammatory substance, cortisol, which is produced by the adrenal glands. In RA, the inflammatory response within the joints is greatly exaggerated – such that the body’s natural supply of cortisol is insufficient to relieve symptoms.
Aside from side effects, one of the dangers of using glucocorticoids is sudden withdrawal. As the body gets used to what it senses as extra “cortisol,” it slows down production of the real thing. Gradually lowering the dose of the corticosteroid gives the adrenal glands time to step-up natural production, thus preventing such withdrawal symptoms as severe weakness and fatigue.
While some RA patients may be leery of corticosteroids, others embrace them – and no wonder, says Dr. Cohen. “They make the patient feel tremendously better.”
Building a Better Corticosteroid
Efforts are underway to develop better and safer corticosteroids. A delayed-release form of prednisone, Rayos, is now available. This preparation, taken before bedtime, releases its prednisone into the system at a time during the night when the adrenal glands are at their lowest activity. The result for patients is an improvement in early morning stiffness.
“People with RA know that symptoms are usually much worse in the mornings,” says Dr. Kirwan. “This delayed release formulation has been shown to get better control of morning stiffness compared to taking corticosteroids in the morning.”
Dr. Kirwan says researchers are looking for other ways to mitigate side effects of corticosteroids without sacrificing therapeutic effects. “One option is to find a new type of substance, called a SEGRA, or selective glucocorticoid receptor agonist, which only affects the inflammation action, not the metabolic one.”
Another involves creating what might be called “smart” corticosteroid injections. “The [corticosteroid] is attached to liposomes (basically a protective enclosure) which naturally home in on places where inflammation is happening,” he says.
As flawed as these drugs may be, clinicians and patients agree, they work.