This study describes the subjective and objective responses of 14 patients following treatment with Compound E. Improvement was noted in muscle and joint pain, functional status, appetite, strength and overall sense of well-being—including the first description of steroid-associated euphoria. In addition, reductions in erythrocyte sedimentation rate and serum gamma globulin were reported, as well as improvement in disease-associated anemia. The biologic effect of Compound E was further supported by studies of drug withdrawal and subsequent re-institution upon disease flare.
Impact on Rheumatology
This landmark study provided the first evidence that corticosteroids could significantly improve the lives of patients suffering from RA, and its results suggested an alternative to the microbial theory of disease pathogenesis. This latter discovery shaped research in the decades to follow, helping steer the field away from viewing RA as primarily the result of an infectious agent and shifting the focus toward therapeutics without anti-microbial properties. The experiments described in this study also relied upon collaboration with industry partners (i.e., Merck and Co.), a foreshadowing of the academic-industry relationship that drives many drug discoveries today.
Following the improvement seen in patients with RA, Hench et al. then began to administer Compound E to lupus patients, with “encouraging results,” and described a patient with myasthenia gravis who improved following treatment with adrenocorticotropic hormone. These point to the widespread applicability of corticosteroids in inflammatory/autoimmune disease.
Chances in the Tournament
Do we love this study? Let us count the ways: the discovery of the therapeutic potential of steroids, evidence of a biochemical basis of RA, initial descriptions of steroid-related side effects, and application to other diseases such as lupus and myasthenia gravis. Oh, and yes, the authors were awarded the Nobel Prize (the following year!) as a result of their decades-long work in this area.
While we believe this study is a clear favorite to win the tournament, it may also be viewed by some readers as a blue blood that needs to step aside and make way for new therapies. Just as many fans have become tired of seeing Duke basketball play in the past 25 NCAA tournaments or Southeastern Conference football teams annually winning the championship game, some may feel that prednisone has already had its day in the sun.
It may also be tempting to overlook this study due to the side effects associated with corticosteroids, as well as numerous studies investigating the ability to reduce our dependence on them.4-6 Even so, it’s important to recognize that all medications have side effects, and as with any drug, medication risk can be mitigated by a cautious, conscientious prescriber and balanced against the potential benefit. With this said, let’s recognize the many positives this precious gift provides to our patients with rheumatic disease and give credit where it’s due.
