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


Oral and intravenous methylprednisolone were equally efficacious for relapses in multiple sclerosis

ACP J Club. 1997 Sep-Oct;127:38. doi:10.7326/ACPJC-1997-127-2-038

Source Citation

Barnes D, Hughes RA, Morris RW, et al. Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis. Lancet. 1997 Mar 29;349:902-6.



To compare the efficacy of intravenous and oral methylprednisolone for patients with acute relapses of multiple sclerosis.


24-week randomized, double-blind, placebo-controlled trial.


6 hospitals in the United Kingdom.


80 patients (median duration of multiple sclerosis 6 y; mean age 38 y; 64% women) with clinically definite multiple sclerosis confirmed by magnetic resonance imaging or evoked potential response. Inclusion criteria were a relapse within the previous 4 weeks that was serious enough to require steroids and age > 16 years. Exclusion criteria were use of steroids or other immunosuppressive drugs in the previous month, pregnancy, inability to give consent, or contraindications to steroids. Follow-up was 85%.


38 patients were allocated to intravenous methylprednisolone, 1 g/d in 100 mL 5% dextrose given over 30 minutes for 3 days, and 42 patients were allocated to oral methylprednisolone, 48 mg/d for 7 days followed by 24 mg/d for 7 days and 12 mg/d for 7 days.

Main outcome measures

The primary outcome measure was a difference between groups of ≥ 1 grade in Kurtzke expanded disability status scale (EDSS) score at 4 weeks. Secondary outcomes were changes in Hauser Ambulatory Index scores and arm-function index scores at 4 weeks. Changes were also measured at 1, 12, and 24 weeks.

Main results

The study had 90% power to detect differences. No difference in recovery was seen between the 2 groups; limited recovery was noted in both groups in the arm-function index. With adjustment for baseline EDSS scores, the mean differences at 4 weeks between the groups in median scores was 0.01 grades (95% CI - 0.46 to 0.60; P = 0.8). The groups did not differ for changes from baseline to 1, 4, 12, and 24 weeks for median EDSS, Hauser Ambulatory Index, or arm-function index scores. The groups also did not differ for cumulative rates of discharge from the hospital. No serious adverse effects were reported by either group.


Oral and intravenous methylprednisolone were equally efficacious for patients who required steroid treatment for relapses of multiple sclerosis.

Sources of funding: Multiple Sclerosis Society of Great Britain and Northern Ireland and, in part, Upjohn (treatment packs).

For article reprint: Dr. D. Barnes, Department of Neurology, Atkinson Morley's Hospital, Wimbledon, London SW20 ONE, England, UK. FAX 44-181-725-4700.


For over 3 decades, arguments have centered around the best route and dose of steroid therapy for acute attacks of multiple sclerosis. These arguments are based on studies that showed a significant but small benefit of cortiocotropin and intravenous methylprednisolone. Short courses of oral steroids have been used, more from convenience and familiarity than from evidence that they are beneficial. Thus, comparison of intravenous and oral methylprednisolone is welcome.

The authors conclude that oral therapy is as effective as the more widely used (at least in North America) intravenous methylprednisolone, when the conclusion could have been that both had an equally minor benefit. Perhaps the limitation of these therapies is best seen in the small change in the Kurtzke EDSS score, a coarse but reasonably reproducible and universally used evaluation tool in clinical trials. The EDSS score (which is heavily weighted for ambulation) increased only 0.5 of a grade in each group by 4 weeks, and 0.5 in the intravenous group and 0.75 in the oral group by 24 weeks. Moreover, 18 of the 36 patients (50%) receiving intravenous therapy and 20 of the 42 patients (48%) receiving oral therapy had no improvement in their EDSS scores—"small change" indeed. In fact, the change was less than in other studies (1, 2), perhaps because this study had a surprisingly large number of very disabled patients in whom change is more difficult to measure and chronicity makes change less likely.

Many of us who have been unconvinced about the benefits of oral therapy from previous studies and experiences will be reluctant to accept the authors' suggestion that we switch from intravenous to oral steroids based on these results. Because the issues are of great practical and financial concern, further studies are urgently needed.

T. Jock Murray, OC, MD
Dalhousie UniversityHalifax, Nova Scotia, Canada


1. Thompson AJ, Kennard C, Swash M, et al. Relative efficacy of intravenous methylprednisolone and ACTH in the treatment of acute relapse in MS. Neurology. 1989;39:969-71.

2. Milligan NM, Newcombe R, Compston DA. A double-blind controlled trial of high dose methylprednisolone in patients with multiple sclerosis: 1. Clinical effects. J Neurol Neurosurg Psychiatry. 1987;50:511-6.