Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Review: Low-dose, short-term corticosteroids reduce joint tenderness and pain in adults who have rheumatoid arthritis

ACP J Club. 1998 Sep-Oct;129:39. doi:10.7326/ACPJC-1998-129-2-039


Source Citation

Gøtzsche PC, Johansen HK. Meta-analysis of short term low dose prednisolone versus placebo and non-steroidal anti-inflammatory drugs in rheumatoid arthritis. BMJ. 1998 Mar 14;316:811-8.


Abstract

Question

In adults with rheumatoid arthritis, can low-dose, short-term corticosteroids (equivalent to prednisolone, ≤ 15 mg/d) reduce joint tenderness and pain and increase grip strength better than placebo or nonsteroidal anti-inflammatory drugs (NSAIDs)?

Data sources

Studies were identified by searching MEDLINE (1966 to September 1997) using the terms glucocorticoids, rheumatoid arthritis, and placebo or comparative study. The Cochrane Controlled Trials Register, bibliographies of relevant studies, and collections of articles of 1 reviewer were also examined.

Study selection

Randomized controlled trials were selected if they studied patients with rheumatoid arthritis; if outcomes were measured within 1 month of treatment initiation; and if oral medication did not exceed the equivalent of prednisolone, 15 mg/d. Studies of combinations of medications were excluded.

Data extraction

Data were extracted in duplicate on the number of patients, nature and dose of treatments, randomization and blinding techniques, inclusion and exclusion criteria, and outcomes (joint tenderness, pain, and grip strength).

Main results

10 studies were included. Approximately two thirds of patients were women, mean age was 55 years, and mean duration of disease was 6 years (range, 2 to 10 y). Prednisolone was used in 6 trials, and prednisone was used in 4 trials; but all analyses assumed that the drugs were equivalent and were reported as prednisolone. Doses were 2.5, 3.0, and 7.5 mg in 1 study each; 10 mg in 3 studies; and 15 mg in 4 studies. 7 trials lasted 7 days; the others varied in length from 5 to 14 days. Meta-analysis that used standard mean differences showed that prednisolone reduced joint tender-ness and pain more than placebo and NSAIDs and increased grip strength more than placebo (Table). Few data on adverse effects were reported.

Conclusions

Low-dose, short-term (≤ 14 d) prednisolone or prednisone therapy for rheumatoid arthritis reduces joint tenderness and pain and increases grip strength better than placebo. It also reduces joint tenderness and pain better than nonsteroidal anti-inflammatory drugs.

Source of funding: Danish Medical Research Council.

For correspondence: Dr. P.C. Gøtzsche, Nordic Cochrane Centre, Rigshospitalet, Department 7112, Tagensvej 18 B, DK-2200 Copenhagen N, Denmark. FAX 45-3545-7007.


Table. Short-term, low-dose prednisolone vs placebo or nonsteroidal anti-inflammatory drugs (NSAIDs) in rheumatoid arthritis

Outcomes Number of studies Comparison Standard mean differences (95% CI)
Joint tenderness 7 Prednisolone vs placebo -1.31 (-1.83 to -0.78)
4 Prednisolone vs NSAIDs -0.63 (-1.16 to -0.11)
Pain 6 Prednisolone vs placebo -1.75 (-2.64 to -0.87)
3 Prednisolone vs NSAIDs -1.25 (-2.24 to -0.26)
Grip strength 6 Prednisolone vs placebo 0.41 (0.13 to 0.69)
4 Prednisolone vs NSAIDs 0.31 (not significant)

Commentary

The meta-analysis by Gøtzsche and Johansen reflects what is seen in clinical practice: A short course of low-dose corticosteroids reduces joint tenderness and pain in adults with rheumatoid arthritis. However, this may not be the most pertinent issue in the corticosteroid debate. Rheumatoid arthritis is a chronic disease with a generally poor long-term outcome. This meta-analysis deals with responses in the first week of treatment and does not address treatment effects thereafter. Moreover, effectiveness, and not adverse effects, was the principal focus of this study. For clinicians prescribing short-term, low-dose prednisone, very little doubt exists about the potent anti-inflammatory actions of corticosteroids. However, there is almost always concern about the difficulty of tapering the dose and the risk for potential adverse effects when maintaining initial doses (1). Therefore, although Gøtzsche and Johansen's meta-analysis concludes that prednisone in low doses may be used intermittently to reduce disease activity, such evidence alone should not promote an exclusive use of this approach. Instead, the use of prednisone in the treatment of patients with rheumatoid arthritis should continue to play a role in a longer-term management strategy that also includes disease-modifying antirheumatic drugs (2).

It is also important to recognize that prolonged use of prednisolone, which is often inevitable when treating rheumatoid arthritis, is frequently associated with such side effects as cataracts, alterations in glucose metabolism, susceptibility to infections, and osteoporosis (3), all of which might require additional management (4).

Johannes W. Bijlsma, MD
University HospitalUtrecht, The Netherlands


References

1. Dennison EM, Cooper C. Corticosteroids in rheumatoid arthritis. BMJ. 1998;316:789-90.

2. Bijlsma JW, Everdingen AA, Jacobs JW. Corticosteroids in rheumatoid arthritis; how best to use them? Clin Immunotherapy. 1995;3:271-86.

3. Saag KG, Kochnke R, Caldwell JR, et al. Low dose long-term corticosteroid therapy in rheumatoid arthritis: an analysis of serious adverse events. Am J Med. 1994;96:115-23.

4. Bijlsma JW. Prevention of glucocorticosteroid induced osteoporosis. Ann Rheum Dis. 1997;56:507-9.