There is conflicting evidence regarding the efficacy of oral steroids in the treatment of exacerbations. In the optic neuritis study referred to previously, there were more relapses in subsequent months in the oral prednisone group than in either the placebotreated or the IVMP-treated group. Many people who have examined these data, however, reject the conclusion of the authors that oral prednisone was responsible for the increased later exacerbation rate.

A Danish study demonstrated the efficacy of oral methylprednisolone (MP) as a treatment for exacerbations. It compared the effects of oral MP therapy and placebo in patients with an episode lasting less than four weeks. 25 patients received placebo, and 26 patients were given 500 mg oral MP once a day for five days, followed by a 10-day drug tapering period. Patients receiving MP did consistently better than those receiving placebo. At eight weeks after the start of treatment, 32 percent of patients in the placebo group had improved by one Expanded Disability Status Scale (EDSS) point, whereas 65 percent of patients taking MP had a similar improvement.

Another study, performed in the United Kingdom, compared oral MP with IVMP: 80 patients with MS were treated within four weeks of the start of an exacerbation. Of these patients, 38 received IVMP (1000 mg/day for three days) and 42 received oral MP (48 mg/day for 7 days, followed by 24 mg/day for seven days and 12 mg/day for the final seven days). Hence, the cumulative dose of methylprednisolone was 3000 mg in the IV group and 588 mg in the oral group. The primary outcome was the difference between the two groups in improvement in the EDSS score of at least one full point after four weeks. No significant difference was found either with respect to this primary outcome or in any other measurement at any stage of the study. The main concerns regarding this study are that there was only a modest effect of treatment in both arms and that therefore a statistical type II error (real difference not being detected) is quite likely to occur. One must remember in this respect that statistical methods are tools that are predominantly developed to detect differences rather than to prove similarities: the absence of proof of difference is not equal to the proof of absence of difference.

It is extremely important that oral treatment with steroids not be prolonged because the complications of long-term treatment are well established. Complications include generalised puffiness, “moon face,” psychosis, peptic ulceration, infections, and acne. Long-term use may even result in serious side effects, such as fractures related to bone softening, aseptic necrosis of bone, cataracts, hypertension, and adrenal insufficiency.

In the opinion of the Committee, treatment with oral steroids, even though it has recently gained some support, is not the preferred treatment for exacerbations, because only rather small studies (applying very different dosages) have been performed and it is not clear whether oral treatment, which in many regimens has to be prescribed longer than intravenous treatment, might increase the risk of side-effects.