6-Methyl Prednisolone in the Treatment of Rheumatoid Arthritis

IN recent years synthetic analogues of cortisone and hydrocortisone have been employed in the treatment of rheumatoid arthritis. Prednisone and prednisolone were first used by Bunim, Pechet, and Bollet in 1955, and since then further reports Although the greater anti-rheumatic effects and lessened risks of sodium retention in these compounds have been advantageous, most workers have been concerned by the increased incidence of dyspepsia and gastro-(luodenal ulceration which attended their use. Because of this and other disadvantages, the search for newer compounds with fewer impleasant side-effects has continued, and recently two new steroids, triamcinolone and 6-methyl prednisolone have been discovered. 6-Methyl prednisolone (Medrone Upjohn), which is the subject of this report, is 6-methyl-A 1-hydrocortisone and differs from prednisolone only in the substitution of a methyl group for an H atom in the 6 alpha position. By means of animal experiments Lyster et al. (1957) have shown it to be three times as potent as prednisolone using the glycogen deposition assay, and twice as potent in anti-inflammatory activity by the granuloma pouch assay. No measurable sodium or water retention was found;, and in fact, a sodium and water diuresis was observed in the experimental animal. 6-Methyl predisolone has also been shown to be less susceptible to enzvmatic reduction bv the liver than prednisolone (Glen et al., 1957). In spite of these encouraging findings the earliest published report of the use of 6-methyl prednisolone in rheumatoid arthritis was disappointing. Boland and Liddle (1957) stated that it possessed no obvious advantage over prednisolone and that both drugs exerted identical effects in equivalent doses. These findings are, however, at variance with the results of Bilka and Melby (1958), who believed that 6-methyl prednisolone was 25 per cent. more effective than prednisolone, while Grater (1958) thought it was one and a half times more potent in the treatment of allergic disorders. Because of these conflicting opinions it was decided to carry out a clinical trial of 6-methyl prednisolone with the object of answering the following questions: 1. What is the potency of 6-methyl prednisolone in comparison with pred-nisolone ? 2. Does 6-methyl prednisolone possess any advantage over prednisolone in the treatment of rheumatoid arthritis? 130