Preliminary clinical trials with 9-alpha-fluoro hydrocortisone acetate in rheumatoid arthritis.

That the properties of adrenal cortical hormones may be modified by relatively minor alterations in their structural formulae is well known. Addition or removal of various chemical radicals and groupings at one or another carbon position in the steroid nucleus may enhance or lessen one or more of the physiological activities of the parent compound. The imagination of chemists has been so stimulated by this fact that literally hundreds of synthetic steroid preparations have been made, and at a rate more rapid than they can be tested therapeutically or experimentally in animals. Because hydrocortisone and cortisone have definite limitations as treatment agents for rheumatoid arthritis, investigators have continued to search for substitutes which might be applied with greater success. We have screened a number of esterified preparations of hydrocortisone and have made clinical comparisons of their anti-rheumatic activity. Recently our attention was attracted to a halogen derivative, 9-alpha-fluoro hydrocortisone acetate, which, though probably not destined as a practical agent for systemic therapy in rheumatoid arthritis, is of interest because it exhibits far greater antirheumatic potency, milligram for milligram, than any steroid we have tested heretofore. Clinical interest in the halogenated derivatives of hydrocortisone was stimulated by results of animal studies which indicated that these compounds possess unusually high glycogenic activity as measured by rat liver glycogen assays for 11-oxygenated corticoids. Fried and Sabo (1953, 1954), Borman and Singer (1954), and Borman, Singer, and Numerof (1954) determined that the 9-alpha-halo derivatives (chloro, fluoro, iodo, and bromo) manifest both