A Rational Approach to the Treatment of Rheumatoid Arthritis: Introduction

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RHEUMATOID ARTHRITIS is a highly complex systemic disorder of unknown etiology. It is characterized by great variations in disease activity and therapeutic response which make it difficult to evaluate the results of treatment. As yet no treatment has proved to be consistently effective. The favorable results that have been achieved with various therapeutic agents often are only temporary and, when relapse occurs, unfortunately an increased dosage of the therapeutic agent does little more than produce toxic reactions.

We have investigated during the past six years the effects of drugs on rheumatoid arthritis of varying severity. The effects of intravenous nitrogen mustard* have been studied for six years (part I), intraarticular nitrogen mustard* for two years (part II), the hydrazides isoniazid and iproniazid** for five years (part III), and the antimalarial agents hydroxychloroquine sulfate and chloroquine phosphate†† for two years (part IV). The drugs were administered singly and also in combination with corticotropin (ACTH) and various corticosteroidsagcortisone acetate,a hydrocortisone,b prednisone,c prednisolone,d hydrocortisone acetate,e hydrocortisone tertiary-butylacetate,f and prednisolone tertiary-butylacetate,g In combination, each drug usually was administered in a dose that alone had little suppressing effect on disease activity. The effects of each drug were observed for one year or longer, during which time the desirable and undesirable actions were evaluated. Combinations of drugs, dosages, and routes of administration were determined which would most effectively suppress disease activity and cause the least number of toxic reactions. Corticotropin and corticosteroid were used sparingly and temporarily in an attempt to avoid undesirable side . . .



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