Intervention review. Corticosteroids for the long-term treatment in multiple sclerosis

Abstract

Background: Short term high dose corticosteroid treatment improves symptoms and short term disability after an acute exacerbation of multiple sclerosis (MS) but it is unknown whether its long-term use can reduce the accumulation of disability.

Objectives: To determine the efficacy and safety of long-term corticosteroid use in MS.

Search strategy: We searched the following bibliographic databases: CENTRAL (Issue 1, 2007), MEDLINE (1966 to February 2007) and EMBASE (1980 to February 2007). In an effort to identify further published, unpublished and ongoing trials we searched reference lists and contacted trial authors and one pharmaceutical company.

Selection criteria: We considered controlled, randomised trials (RCTs), with or without blinding, of long term treatment (i.e. longer than 6 months) of any type of corticosteroid in MS, irrespective of disease course.

Data collection and analysis: Reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information.

Main results: Three trials, all classified at high risk of bias, contributed to this review (Miller 1961; BPSM 1995; Zivadinov 2001) resulting in a total of 183 participants (91 treated). Corticosteroid therapy did not reduce the risk of being worse at the end of follow-up (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.26 to 1.02) but there was a substantial heterogeneity between studies (I(2): 78.4%). I. v. periodic high dose methylprednisolone (MP) was associated with a significant reduction in the risk of disability progression at 5 years in relapsing-remitting (RR) MS (OR 0.26, 95% CI 0.10 to 0.66), while oral continuous low dose prednisolone was not associated with any risk reduction in disability progression at 18 months (OR 1.23, 95% CI 0.43 to 3.56). Risk of experiencing at least one exacerbation at end of follow-up was not significantly reduced with corticosteroid treatment (OR 0.36; 95% CI 0.10 to 1.25).Only one study recorded adverse events: in one patient i. v. MP was discontinued after the fourth pulse when he developed acute glomerulonephritis; a second patient was removed from the study after the fifth i. v. MP pulse because of severe osteoporosis.

Authors' conclusions: There is no enough evidence that long-term corticosteroid treatment delays progression of long term disability in patients with MS. Since one study at high risk of bias showed that the administration of pulsed high dose i. v. MP is associated with a significant reduction in the risk of long term disability progression in patients with RR MS, an adequately powered, high quality RCT is needed to investigate this finding.

Plain language summary

The long-term use of anti-inflammatory corticosteroids for treating multiple sclerosis
Multiple sclerosis is an inflammatory disease affecting the brain and spinal cord. It results in episodes of neurological deficit which recover (relapses) as well as accumulation of sustained disability with the passage of time. Corticosteroids are potent anti-inflammatory drugs. It is postulated that long-term use of steroids may reduce the accumulation of disability. The reviewers found three studies addressing this issue. A meta-analysis showed a trend towards a beneficial effect of long-term corticosteroids on accumulation of disability; however only two small studies contributed to this result. It was not possible to reliably comment on the effect of long-term corticosteroids on the frequency of relapses. Side effects were poorly documented. Therefore rigorous randomised controlled trials of this treatment are warranted.

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ORCID for Ian Galea: orcid.org/0000-0002-1268-5102

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