Meta-analysis of short term low dose prednisolone versus placebo and non-steroidal anti-inflammatory drugs in rheumatoid arthritis

BMJ 1998;316:811-818 ( 14 March )

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Meta-analysis of short term low dose prednisolone versus placebo and non-steroidal anti-inflammatory drugs in rheumatoid arthritis

Editorial by Dennison and Cooper

Peter C Gøtzsche, director, Helle Krogh Johansen, senior researcher.

Nordic Cochrane Centre, Rigshospitalet, Department 7112, Tagensvej 18 B, DK-2200 Copenhagen N, Denmark

Correspondence to: Dr Gøtzsche p.c.gotzsche{at}cochrane.dk

Objective: To determine whether short term, oral low dose prednisolone ( $=<$ 15 mg daily) is superior to placebo and non-steroidalanti-inflammatory drugs in patients with rheumatoid arthritis.
Design: Meta-analysis of randomised trials of oral corticosteroids compared with placebo or a non-steroidal anti-inflammatorydrug.
Setting: Trials conducted anywhere in the world.
Subjects: Patients with rheumatoid arthritis.
Main outcome measures: Joint tenderness, pain, and grip strength. Outcomes measured on different scales were combinedby using the standardised effect size (difference in effect dividedby SD of the measurements).
Results: Ten studies were included in the meta-analysis. Prednisolone had a marked effect over placebo on joint tenderness(standardised effect size 1.31; 95% confidence interval 0.78 to1.83), pain (1.75; 0.87 to 2.64), and grip strength (0.41; 0.13to 0.69). Measured in the original units the differences were12 (6 to 18) tender joints and 22 mm Hg (5 mm Hg to 40 mm Hg)for grip strength. Prednisolone also had a greater effect thannon-steroidal anti-inflammatory drugs on joint tenderness (0.63;0.11 to 1.16) and pain (1.25; 0.26 to 2.24), whereas the differencein grip strength was not significant (0.31; $-$ 0.02 to 0.64). Measuredin the original units the differences were 9 (5 to 12) tenderjoints and 12 mm Hg ( $-$ 6 mm Hg to 31 mm Hg). The risk of adverseeffects during moderate and long term use seemed acceptable.
Conclusion: Prednisolone in low doses ( $=<$ 15 mg daily) may be used intermittently in patients with rheumatoid arthritis,particularly if the disease cannot be controlled by other means.

Key messages

Prednisolone in low doses $---$ that is, no more than 15 mg daily $---$ is highly effective in patients with rheumatoid arthritis
The risk of adverse effects is acceptable in short, moderate, or long term use
Oral low dose prednisolone may be used intermittently in patients with rheumatoid arthritis, particularly if the disease cannot be controlled by other means
Further short term placebo controlled trials to study the clinical effect of prednisolone or other oral corticosteroids are no longer necessary

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