Benefits and Risks of Low-dose Glucocorticoid Treatment in the Patient With Rheumatoid Arthritis

Arthur Kavanaugh; Alvin F. Wells


Rheumatology. 2014;53:1742-1751. 

In This Article

Abstract and Introduction


Glucocorticosteroids (GCs) have been employed extensively for the treatment of rheumatoid arthritis (RA) and other autoimmune and systemic inflammatory disorders. Their use is supported by extensive literature and their utility is reflected in their incorporation into current treatment guidelines for RA and other conditions. Nevertheless, there is still some concern regarding the long-term use of GCs because of their potential for clinically important adverse events, particularly with an extended duration of treatment and the use of high doses. This article systematically reviews the efficacy for radiological and clinical outcomes for low-dose GCs (defined as ≤10 mg/day prednisone equivalent) in the treatment of RA. Results reviewed indicated that low-dose GCs, usually administered in combination with synthetic DMARDs, most often MTX, significantly improve structural outcomes and decrease symptom severity in patients with RA. Safety data indicate that GC-associated adverse events are dose related, but still occur in patients receiving low doses of these agents. Concerns about side effects associated with GCs have prompted the development of new strategies aimed at improving safety without compromising efficacy. These include altering the structure of existing GCs and the development of delayed-release GC formulations so that drug delivery is timed to match greatest symptom severity. Optimal use of low-dose GCs has the potential to improve long-term outcomes for patients with RA.


The Role of Glucocorticoids in the Treatment of RA

Glucocorticosteroids (GCs) have a long history of good efficacy and safety in the treatment of RA. This has resulted in their inclusion in guidelines for the management of this disease. For example, the European League Against Rheumatism (EULAR) guidelines recommend that GCs be added at low to moderately high doses to synthetic DMARD monotherapy (or combinations of synthetic DMARDs) since they have been shown to provide benefit as an initial short-term treatment. However, it is also generally recommended that GCs should be tapered as rapidly as clinically feasible.[1] The Canadian Rheumatology Association treatment recommendations state that GCs (oral, intramuscular or intra-articular) can be added to DMARD therapy as part of the initial treatment strategy for patients with RA, and may be an option for managing flares as bridge therapy while waiting for a DMARD to take effect, or for symptom control if no other options exist.[2]

While the use of GCs in patients with RA is supported by clinical trial results, there is still some concern surrounding their use because of potential associations with clinically important adverse events, particularly when they are administered at high doses and/or for long duration.[3–5] While caution is certainly warranted in the use of GCs in patients with RA, results from a large number of studies have indicated that combination of low doses of these agents with DMARDs may have significant benefit with respect to joint preservation and also acceptable safety. In addition, new GC molecules are being developed in an effort to improve their efficacy and tolerability.

The aim of this article was to systematically review the efficacy (radiological and clinical outcomes) and safety of low-dose GCs when used as part of treatment regimens for patients with RA. The analysis included studies in which GCs were administered at low doses (≤10 mg/day prednisone equivalent). In some trials, GCs were delivered at higher doses for a short interval prior to tapering to a dose ≤10 mg/day.