Cortisone and Its Analogues in the Treatment of the Rheumatic Diseases

Cortisone and ACTH have been the focus of high hopes and grave fears and the centre 'of heated argument ever since their dramatic effect on rheumatoid arthritis was first announced by Philip Hench of the Mayo Clinic in I949. Because of the suffering caused by rheumatoid arthritis and the long history of frustration and failure to find a cure, they were hailed at first with little critical assessment. Though the reports from the Mayo Clinic spoke always of ' investigation' never of ' treatment,' in the first wave of enthusiasm this discrimination was ignored. Medical judgment was hampered by the scarcity of cortisone. When supplies increased it became evident that the drug was a suppressive agent, not a cure, and that its use was complicated by side effects. The first trial of cortisone resulted from years of study of rheumatoid arthritis by Philip Hench. He had been impressed by the fact that the symptoms and signs of the disease were alleviated irk pregnancy and an attack of jaundice. Hench had come to the conclusion that there might be an anti-rheumatic substance ' X' stimulated by these two conditions. E. C. Kendall, also of the Mayo Clinic, had isolated, among other adrenal cortical steroids, compound E, later called cortisone, and a small amount was available for trial. Together Hench and Kendall decided to investigate the effect of cortisone in rheumatoid arthritis. Originally cortisone was manufactured from ox bile and the expense of commercial preparations was high. Continuous efforts have been made by pharmaceutical firms all over the world to use cheaper starting materials and less expensive processes. They have succeeded and the cost of cortisone has been lowered. In I949 Hench, Kendall, Slocumb and Polley published their first account of the effects of cortisone and ACTH in rheumatoid arthritis and in rheumatic fever. During the next few years, as physicians began to weigh up the clinical value of cortisone and ACTH in the treatment of rheumatoid arthritis, a wide divergence of opinion became apparent. Reports of large series of cases treated satisfactorily with cortisone over long periods were published from Denmark (Fischer and BrochnerMortensen, 1953), France (Coste et al., 1953), the United States (Ward et al., 1953; Boland, I955; and Bunim et al., 1955), and Great Britain (Copeman et al., 1952). In 1954, I955 and 1957 the Medical Research Counciland Nuffield Joint Committee published the results of trials in which they compared the effects of cortisone and aspirin in early cases of rheumatoid arthritis. They found that there was no difference between the two groups. In 1957 the Empire Rheumatism Council published the results of a three-year trial of cortisone and aspirin, given cont-inuously in later cases of rheumatoid arthritis. They also found no statistical difference between the effects of the two drugs. These trials have been criticized on the grounds that with the techniques used it was perfectly possible for some patients to respond to cortisone and for others to respond to aspirin, and yet for there to be no statistical difference between the two groups as a whole. Physicians who have used cortisone and ACTH for some years in the treatment of rheumatoid arthritis and have reached the conclusion that they have a practical place in therapy have recognized that up to date there are two outstanding limitations: