CHLOROQUINE COMBINED WITH CYCLOSPORINE IN RHEUMATOID-ARTHRITIS - MORETHAN THE ADDITION OF 2 DRUGS ALONE

Combination therapy in rheumatoid arthritis (RA) with 2 or more diseas e modifying antirheumatic drugs (DMARD) is theoretically attractive if the drugs exert additional or even synergistic effects and have diffe rent toxicity patterns to avoid cumulative toxicity. The combination o f cyclosporin A (CsA) with chloroquine has shown in in vitro studies a synergistic ability to inhibit the proliferation of peripheral blood mononuclear cells and clonal T cells and the production of interferon gamma by clonal T cells. This synergy is probably based on different m echanisms of action of the 2 drugs: CsA primarily inhibits the product ion of interleukin 2 (IL-2) (and other cytokines) at the level of tran scription, whereas chloroquine primarily inhibits the responsiveness o f T cells to IL-2 stimulation. To evaluate whether these in vitro data can be extrapolated in vivo, a large 2 phase trial has been initiated in the Netherlands in which the combination of CsA with chloroquine i s evaluated in patients with RA.