Corticosteroids or ACTH for acute exacerbations in multiple sclerosis

Article type
Authors
Filippini G, Brusaferri F, Citterio A, Ciucci G, Midgar R, Sibley W
Abstract
Background: To examine the efficacy of corticosteroids in reducing the short and long-term morbidity from Multiple Sclerosis (MS). Primary outcomes were: a) no improvement or worsening in disability grade on Expanded Disability Status Scale (EDSS) or equivalent score within a period no longer than 12 weeks from randomisation; b) proportion of patients who relapsed at 6 months, 1 year, 2 years, 3 years since randomisation; c) proportion of patients who had disability progression from 12 weeks until the end of the follow-up period.

Methods: A search strategy developed for the Cochrane MS Group completed with handsearching and personal contacts with trialists and pharmaceutical companies were used. All unconfounded, randomised controlled trials comparing corticosteroids or ACTH to placebo in patients with MS, treated for acute exacerbation, without any age or severity restrictions, were evaluated. Two authors independently assessed trials' quality and extracted data. A third author checked them. Data analysis was performed using Review Manager 4.0.4.

Results: Six trials contributed to this review; a total of 377 participants (199 treatment, 178 placebo) were randomised. The drugs analysed were methylprednisolone (MP) (four trials, 140 patients) and ACTH (two trials, 237 patients). One trial of intramuscular ACTH accounted for 197 of the total 377 subjects studied (52%). Overall, methylprednisolone or ACTH showed a protective effect against the disease getting worse or stable within five weeks from randomisation (odds ratio [OR]= 0.37, 95% confidence interval [CI] 0.24-0.57) with some but non significant greater effect for MP and intravenous administration. Short (five days) or long (15 days tapering) duration of treatment with MP did not show any significant difference. In one study (total n=51) no difference between steroids and control in the prevention of new exacerbations or improvement in long-term disability was detected. No data are available beyond one year of follow-up to indicate whether steroids have any effect on long-term progression. Adverse events were reported in four trials. Gastrointestinal symptoms occurred significantly more often in the oral, high-dose MP treated group (38.0%) than in the placebo group (8.0%). Minor psychic disorders including insomnia were significantly more frequent in patients treated with steroids than in controls (OR=4.47, 95% CI 1.91-10.46). Treatment with oral, high-dose MP greatly accounted for this adverse event. Hypertension was not reported in the three trials with MP. Development of infections was never reported in the four trials reporting adverse events.

Conclusions: We found evidence favouring steroids for acute exacerbation in MS patients. However, gastrointestinal symptoms and minor psychic disorders are associated with oral, high-dose MP administered for 15 days. Judicious use of this best available evidence should lead to better informed decisions both by physicians and patients. Data are insufficient to reliably estimate effect of steroids on other important outcomes, including prevention of new exacerbations and long-term disability. A subsequent Cochrane review will review trials involving "head to head" comparisons of different corticosteroids in order to identify risk/benefit ratio of different drugs, regimen and administration routes. Moreover, studies assessing long term risk/benefit and adverse effects of corticosteroids in MS patients are urgently needed.