Corticosteroids or ACTH for acute exacerbations in multiple sclerosis

Abstract

Background: Corticosteroids are commonly used to improve the rate of recovery from acute exacerbation in multiple sclerosis (MS) patients. However, it is unclear just how effective these agents are and which is the best treatment schedule (type of drug, dose, frequency, duration of treatment and route of administration). This review is un update of the Cochrane Review, "Corticosteroids or ACTH for acute exacerbations in multiple sclerosis," first published in The Cochrane Library 2000, Issue 4. Objectives: Primary objectives were to determine the effects of corticosteroids and ACTH for the treatment of MS patients with acute exacerbation in terms of improvement of disability; reduction of risk of new exacerbations during follow-up; and prevention of disability progression at long-term follow-up. Secondary objectives included the frequency and severity of adverse effects and their acceptability in the light of benefits; the different effects of corticosteroids according to different doses and drugs, routes of administration, length of treatment and interval of time between onset of symptoms and randomisation, based on indirect comparisons; the different treatment effects according to disease course and the effect of corticosteroids or ACTH on magnetic resonance imaging as a surrogate marker of disease activity. Search methods: The Trials Search Co-ordinator of the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group searched the Group's Specialised Register, which, among other sources, contains the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 2), MEDLINE, EMBASE, CINAHL, LILACS, PEDro and clinical trials registries (31 March 2013). The review authors undertook handsearching and contacted trialists and pharmaceutical companies. Selection criteria: All randomised, double-blind trials comparing corticosteroids or ACTH versus placebo in MS participants during acute exacerbations, regardless of age or severity, were evaluated. Data collection and analysis: Two review authors selected trials for inclusion, assessed the risk of bias and extracted data independently. Disagreements were resolved by consensus among review authors. Study authors were contacted for additional information. Main results: Six trials, published between 1961 and 1998, contributed to this review. The current update did not identify new trials. A total of 377 participants (199 treatment, 178 placebo) were randomly assigned. The drugs analysed were methylprednisolone (MP) (four trials, 140 participants) and ACTH (two trials, 237 participants). Overall, administration of MP or ACTH favoured recovery from acute exacerbation in MS participants: use of either agent decreased by more than 60% the probability of the condition getting worse or stable within the first five weeks of treatment (odds ratio (OR) 0.37, 95% confidence interval (95% CI) 0.24 to 0.57; reduced disability of 1.5 points in the Kurtzke Expanded Disability Status Scale (EDSS) score at the first week of therapy, mean difference -1.47, 95% CI -2.25 to -0.69). The overall quality of evidence according to GRADE levels was moderate. Evidence was insufficient to show whether steroids or ACTH treatment prevented new exacerbations and worsening of long-term disability. Indirect comparisons suggest a significantly greater effect of MP versus ACTH, with MP conferring greater benefit compared with ACTH (OR 0.20, 95% CI 0.09 to 0.45 vs OR 0.46, 95% CI 0.28 to 0.77), and with intravenous MP proving more effective than oral MP (OR 0.12, 95% CI 0.04 to 0.42 vs OR 0.29, 95% CI 0.10 to 0.89) in decreasing the risk of getting worse or stable within the first five weeks of treatment. The time interval from onset of exacerbation to start of treatment administration does not seem to influence the outcome. Short-term (five days) courses of intravenous MP seem to be more effective than long-term treatment (15 days) (OR 0.13, 95% CI 0.02 to 0.75 vs OR 0.22, 95% CI 0.09 to 0.57). No data are available beyond one year of follow-up to allow evaluation of any effect on long-term progression. One study reported that short-term treatment with intravenous high-dose MP was not associated with adverse events. However, gastrointestinal symptoms and affective disorders were significantly more common in the oral high-dose MP group than in the placebo group. Weight gain and edema were significantly more frequent in the ACTH group than among controls. Authors' conclusions: We found evidence that corticosteroids, notably MP, are effective in the treatment of acute exacerbation, increasing the probability of ameliorating the episode and speeding up patient recovery. Data were insufficient to permit reliable estimation of the effects of corticosteroids on prevention of new exacerbations and long-term disability.