"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. "Basically you want as low a dose as possible of corticosteroids and for as short a duration as possible.”

Dr. Massarotti says prednisone’s primary utility in rheumatoid arthritis 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 is extra “cortisol” on board, 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

Given that, efforts are underway to develop a better and safer corticosteroid – and with some recent success. Horizon Pharma just received Food and Drug Administration approval for a delayed-release form of prednisone, Rayos. This preparation, dosed 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 sitffness, one of the hallmarks of RA.

“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.” In June 2012, Dr. Kirwan co-authored a review of time-released prednisone for Therapeutic Advances In Musculoskeletal Disease.

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.

“If you can develop a safe steroid, that would be phenomenal,” Dr. Cohen says.

Because flawed as these drugs may be, clinicians and patients agree, they work.