Corticosteroids--from an idea to clinical use.

Corticosteroids form the basis of treatment in many inflammatory rheumatic diseases, both as systemic treatment and as treatment with local injections to reduce inflammation. In 1948 the first systemic treatment of a patient with a rheumatic disease was given to a woman with severe rheumatoid arthritis (RA); the impressive effect in this patient, and in another 15 patients, was reported by Dr Hench and co-workers in 1949. Systemic corticosteroid treatment was rapidly adopted and used not only for patients with RA but also for those with other rheumatic diseases such as systemic lupus erythematosus-as well as other disorders such as asthma-with a similar positive effect. In the following year, 1950, the Nobel Prize was awarded for the discovery of the structure and biological effects of the adrenal cortex hormones. This open trial was followed by several controlled trials conducted in the UK in which the effects of cortisone were compared with the effects of aspirin in patients with RA-interestingly, without any significant clinical benefit for the cortisone-treated patients. It was not until 1959, in yet another multi-centre trial in Britain, that a significant effect on functional capacity and general well-being was reported after 2 years of treatment with prednisolone, compared to aspirin, in patients with early RA. Despite the dramatic effects that were observed in the severely ill RA patients reported by Hench and co-workers it took 10 years to demonstrate that this effect was superior to the effect of aspirin when the two compounds were compared in controlled trials. Why was this so? One explanation could be in the study designs and the different outcome measures used in the various studies. Perhaps the results in the first comparative studies would have been different if individual response criteria had been used. This is discussed in this chapter.