This is a review of the evolution of the use prednisone in the treatment of rheumatoid arthritis (RA). Cortisone was introduced in 1949 and shortly thereafter, the Mayo investigators found that low divided doses with slow tapering were effective and caused fewer side effects. In 1959, a British double blind 2 year study of prednisolone treatment in early RA demonstrated effectiveness and reduced bony erosions. This experience was lost over time and empiricism and efforts to reduce side effects dominated practice for the next 35 years. Since 1995, a number of controlled studies of low single daily doses of prednisone in early RA have been reported by European investigators. They have shown clinical improvement, reduced bony erosions, augmentation of the effect of dmards and few side effects. During the last 25 years, the molecular actions of glucocorticoids have been elucidated. The time relationship of the dose to the biologic and clinical effects has been established. As a result of the information on the diurnal effect of glucocorticoids and the documentation of the effect occurring 5-6 hours after the dose and dissipating by 24 hours, a delayed release preparation of prednisone has been developed. With the rediscovery of the effectiveness of low single daily morning dose of prednisone in early RA by controlled studies and the demonstration of the onset and duration of the clinical effect of low dose of prednisone, it is now possible to use low doses of prednisone rationally and effectively in the treatment of RA. It remains to be determined whether a single morning, single evening or a twice a day low dose is the most effective and safe. It is doubtful if the new delayed release prednisone is any more effective than the usual immediate release prednisone if given at the same time.
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