Objectives: To perform a systematic review of low-dose corticosteroid efficacy in the moderate term for the treatment of rheumatoid arthritis (RA).
Search strategy: We conducted a search in MEDLINE from 1966 to 1998, using the keywords "corticosteroids" and "rheumatoid arthritis". We also handsearched all issues of Arthritis and Rheumatism and the Scandinavian Journal of Rheumatology from their dates of first publication to 1994. Furthermore, we examined all Arthritis and Rheumatism abstracts over the 15 year period preceding 1994. References of all identified studies were searched for relevant trials. Authors of unpublished manuscripts were contacted.
Selection criteria: Studies were selected by two independent reviewers (LC, KS) using a set of predetermined criteria. Specifically, we required that trials be randomized or cross-over and report at least one of the following outcome measures in a quantitative manner: joint tenderness, joint swelling, grip strength, or erythrocyte sedimentation rate (ESR). We also required that trials be of at least three months duration and use prednisone (or a comparable corticosteroid preparation) at a mean dosage of less than or equal to 15 mg/day. We included studies that used either placebo or active drug controls (i.e., comparative studies).
Data collection and analysis: We compared the effectiveness of prednisone to placebo and/or active controls using a fixed effects model for continuous data. A chi square test for homogeneity was performed, and where heterogeneity existed a random effects model was used. We reported results for all available outcomes recommended by the Outcome Measures for Rheumatology Trials (OMERACT) group. These included the number of tender and swollen joints, pain, functional status and ESR. Grip strength was also evaluated. Standardized mean differences (SMD) were used for outcomes assessing the same concept with different scales (eg. swollen joint counts).
Main results: Very few studies directly assessed the effectiveness of corticosteroids for RA treatment and many were of poor methodologic quality. Only seven of 34 studies identified by our search met criteria for inclusion. Our results indicated that corticosteroids were significantly more effective than placebo controls for four of six outcomes assessed [standardized mean difference for tender joints = -0.37 (95%CI: -0. 59, -0.14), swollen joints = -0.41 (-0.67, -0.16), pain = -0.43 (-0. 74, -0.12), and functional status = -0.57 (-0.92, -0.22)]. The results for grip strength and ESR were not significant [GS = +0.30 (-0.19, +0.80), weighted mean difference (WMD) for ESR = -7.03 (-18. 06, +4.01)]. The single trial that compared prednisone to aspirin indicated no statistically significant difference between these groups for joint tenderness (0.10 (-0.35, +0.55) and for ESR [0.00 (-11.09, +11.09]. Overall, the four outcomes assessed in the single trial that compared prednisone to chloroquine suggested that the effectiveness of these two agents is similar [SMD for joint tenderness = +0.23 (-0.30, +0.75), swollen joints = +0.43 (-0.11, +0. 96), functional status = -0.27 (-0.80, +0.26), and WMD for ESR = -16. 00 (-30.58, -1.42)].
Reviewer's conclusions: Based on the limited data available, moderate-term prednisone treatment of RA appears to be superior to placebo and comparable to treatment with aspirin or chloroquine in improving several common rheumatoid arthritis disease activity measures.