The intelligent use of systemic glucocorticoids in rheumatoid arthritis

Abstract

Glucocorticoids (GC) have potent anti-inflammatory and immunomodulatory effects and are widely used in the management of rheumatoid arthritis in combination with other disease-modifying anti-rheumatoid drugs. Concern about the risk of adverse effects may be to some extent misplaced as low to moderate doses of GC have different mechanisms of action and risk profiles compared with high doses. This review discusses the current understanding about the different modes of action of GC, their strong disease-modifying properties and the efforts at improving the therapeutic ratio of GC through the development of new drugs which promise greater safety such as selective GC receptor agonists, liposomal GC and modified-release (MR) prednisone.

Keywords::

• glucocorticoids
• liposomal delivery
• modified-release prednisone
• nitrosteroids
• rheumatoid arthritis
• selective glucocorticoid receptor agonists

Financial & competing interests disclosure

Horizon Pharma have paid less than GB£10,000 to JR Kirwan to pay for travel costs to attend meetings and as an educational grant to support research on modified-release prednisone. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Glucocorticoids (GC) exert their anti-inflammatory and immunosuppressive effect at cellular and molecular level through various mechanisms, which can be broadly defined into genomic and non-genomic.

• Low- and high-dose GC have different mechanisms of action and consequently different therapeutic and adverse effects.

• Low-dose GC reduce the acute phase response and inhibit radiographic joint damage in early rheumatoid arthritis (which may persist after discontinuation of therapy) and may be considered the strongest disease-modifying anti-rheumatoid drugs.

• Optimal use of GC with other disease-modifying anti-rheumatoid drugs such as methotrexate may prevent or delay the need for costly biologic therapies.

• Patients at risk of GC-induced osteoporosis should receive appropriate bone protection.

• Patients with rheumatoid arthritis on low to medium doses of prednisone who still experience a long duration of morning stiffness, may benefit from modified-release prednisone.

Notes