New perspectives of secondary and tertiary therapy for rheumatoid arthritis.

Rheumatoid arthritis continues to be recognised as a disorder with a variable prognosis, but recent studies have emphasised its potential for shortening life span. Epidemiological, genetic, and natural history studies have helped to identify patients who are at risk for the development of more aggressive disease earlier in their clinical course, and rheumatologists are willing to be more aggressive in their treatment now as their armamentarium expands. Earlier separation of drugs into anti-inflammatory and immunomodulatory agents becomes irrelevant as these concepts change and drugs fulfil both definitions. Sequences of therapy continue to be dictated by the potential of toxicity and generally follow rather than precede disease progression. The addition of several new agents to the algorithms of therapy against rheumatoid arthritis raises questions about their effects and place in therapeutic regimens, especially as concerns auranofin, sulphasalazine, methotrexate and cyclosporin. Combination therapy is currently at the end of the drug line, but the therapeutic horizon beckons with the potential of biological agents aimed at the restoration of immune balance.