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Are Long-Term Very Low Doses of Prednisone for Patients with Rheumatoid Arthritis as Helpful as High Doses Are Harmful?
- Theodore Pincus, MD;
- Tuulikki Sokka, MD, PhD; and
- C. Michael Stein, MD
- Vanderbilt University Medical Center Nashville, TN 37232
Treatment of rheumatoid arthritis with corticosteroids has evoked controversy for half a century. Extremely successful initial clinical results (1) led to the awarding of the 1950 Nobel Prize in Medicine to Kendall, Reichstein, and Hench. Some early clinical trials indicated that corticosteroids had “disease-modifying” properties in retarding radiographic progression (2). However, it was soon recognized that severe toxicities associated with the long-term pharmacologic doses of prednisone used at that time (20 to 40 mg) almost invariably outweighed any benefits (3). By the late 1950s, clinicians were taught that while occasional corticosteroids might be needed for acute life-threatening rheumatoid vasculitis or severe disease flares, long-term corticosteroid treatment had no place in the management of most patients with rheumatoid arthritis.
A reassessment began during the 1980s, based in part on recognition of severe long-term outcomes of rheumatoid arthritis (4, 5). A small clinical trial indicated a nonsignificant advantage with 5 mg of prednisone versus placebo (6). A more recent clinical trial reported by Kirwan (7) has confirmed that corticosteroid dosages as low as 7.5 mg/d for 2 years have “disease-modifying” properties in slowing radiographic progression. Nonetheless, corticosteroids continue to be regarded generally as temporary “bridge” therapy rather than as a long-term therapy in rheumatoid arthritis, particularly because high doses have been associated with higher mortality rates (8, 9) and doses as low as 10 mg have been associated with bone loss (10).
Clinical practice and the medical literature are not always congruent. In 1990, 75% of 532 patients monitored in seven U.S. private practices were taking low-dose corticosteroids (11). Patients who receive corticosteroids have more severe disease, confounding retrospective assessment of their long-term risks. Furthermore, patients in earlier studies (8, 9) had …
