Failure to Recognize Efficacious Treatments: A History of Salicylate Therapy in Rheumatoid Arthritis

FAILURE TO RECOGNIZE EFFICACIOUS TREATMENTS: A HISTORY OF SALICYLATE THERAPYIN RHEUMATOID ARTHRITIS JAMES S. GOODWIN* andJEAN M. GOODWINf Although we live in an age of scientific medicine, it is important to recognize that decisions regarding the therapy of specific diseases are sometimes made as much on an irrational basis as they are on a logical, scientific one. How else can one explain the sustained popularity of injections of antibiotics or vitamin B- 12 as a treatment for the common cold despite the entire body of medical knowledge and the current pressures of peer review? Thus it is important to try to understand the "nonscientific" reasons certain therapies gain early and universal acceptance , while others are ignored. Throughout the long history of medicine there has been a trail of useless and sometimes dangerous remedies for various diseases. The concept of the "placebo effect" is familiar to most physicians; therefore, it is easy for us to understand how our predecessors, and even we, might fool ourselves into supporting an inefficacious treatment. The subject of this paper is a phenomenon which is the converse of the persistent use of inefficacious drugs or treatments, namely, the persistent failure to use a drug that is ultimately shown to be efficacious. To illustrate this phenomenon we will describe the history of the use of high-dose salicylates for the treatment of rheumatoid arthritis. While there is universal agreement today that high-dose salicylate treatment is highly efficacious and, indeed, is the backbone of the treatment of rheumatoid arthritis [1, 2], this idea did The authors thank Drs. Jonathon Abrams, Richard Goldman, William Hardy, David Law, John Samet, Robert Senescu, R. G. Strickland, Ralph Williams, and Walter Winslow for their helpful criticisms of early versions of this paper, and Mrs. Kathleen Aragon for her assistance in preparation of the manuscript. *Division of Gerontology, Department of Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131. tDepartment of Psychiatry, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131.© 1981 by The University of Chicago. All rights reserved 0031-5982/82/2501-0252$01.00 78 I James S. Goodwin andJean M. Goodwin ¦ Salicylate Therapy in Rheumatoid Arthritis not evolve until the mid-1950s—70 years after the introduction and widespread use of salicylates in clinical medicine. History of Salicylates Extracts of the willow tree (Latin, salix) had been used and endorsed by Hippocrates, Pliny, Galen, and other ancient practitioners for the relief of pain and fever [3]. In 1763 Reverend Stone reported to the British Royal Society that willow bark extract (salicylate) could be substituted for the more expensive cinchona bark extract (quinine) in the treatment of pain and fever [4]. Whether because of difficulties in obtaining the drug or for other reasons, salicylates were never in widespread use until the last quarter of the nineteenth century, when simple and inexpensive ways of synthesizing the agents were discovered. Several investigators in the 1870s reported on the use of salicylates for analgesia [5], antipyresis [6], and in the treatment of rheumatic fever [5, 7]. Within a very few years high-dose salicylates were the treatment of choice for acute rheumatic fever. Between 1888 and the present, all medical textbooks we reviewed recommended high-dose salicylates for rheumatic fever (10—30 grains every 3-4 hr in adults [8-10]). Indeed, Osier wrote in 1905 that "the majority of observers agree that they [salicylates] also protect the heart, shorten the course, and render relapse less likely" [10]. Salicylates in the Treatment of Rheumatoid Arthritis While it is relatively easy to trace the use of salicylates back into antiquity , it is difficult to find convincing evidence for the existence of rheumatoid arthritis before the seventeenth century. After reviewing medical writings, literature, painting, and paleopathology for clinical descriptions or pathologic changes of rheumatoid arthritis, Short proposed that the disease may have evolved in the past 300 yr [H]. In any case, by 1800 the disease was differentiated from the infectious (gonorrhea, lues, tuberculosis), acute (gout, rheumatic fever), and degenerative forms of arthritis. In 1859 Garrod first introduced the term "rheumatoid arthritis" and provided an excellent clinical description of the disease [12]. During the early nineteenth century the most...