Rationale opf the cyclosporine and methotrexate combination to control aggressive rheumatoid arthritis

The therapy of rheumatoid arthritis (RA) has undergone profound changes over the last five years. What was once an approach based on clinical practice without any strong biological or pharmacological roots has now become directed towards questions of the cell populations and molecules involved in the various phases of joint and bone damage. This has led to the introduction of innovative therapeutic combinations based on a pivotal drug such as methotrexate (MTX), which is effective on activated T cells and macrophagic-monocytic cytokines, and drugs that act another targets such as cyclosporine (CsA). CsA is an immunosuppressant of the genes of interleukin 2 (Il2) and interferon g that is also capable of depressing other phlogosis-mediating genes by blocking the nuclear migratuon of NF-AT, a crucial transcription factor. The domonstrated efficacy of CsA (and MTX) on the progression of erosions make it one of the most attactive therapeutic combinations. This paper discusses the characteristics of the patients for whom the CsA + MTX combination is most suited as well as its medium-term safety profile.