Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis. A randomised controlled trial comparing rehabilitation against standard therapy in multiple sclerosis patients receiving intravenous steroid treatment. Methylprednisolone in multiple sclerosis: a comparison of oral with intravenous therapy at equivalent high dose. A placebo-controlled, randomized, double-masked, variable dosage, clinical trial of azathioprine with and without methylprednisolone in multiple sclerosis.
An intravenous rather than oral course of methylprednisolone is often prescribed for treating acute relapses in multiple sclerosis (MS) despite the lack of evidence to support this route of administration. Our double-blind placebo-controlled randomised trial was designed to compare the efficacy of commonly used intravenous and oral steroid regimens in promoting recovery from acute relapses in MS.
                42 patients with clinically definite relapse in MS received oral, and 38 intravenous, methylprednisolone. Clinical measurements at entry and at 1 week, 4 weeks, 12 weeks, and 24 weeks included Kurtzke's expanded disability status scale (EDSS), Hauser's Ambulatory Index, and an arm-function index. The primary outcome criterion was a difference between the two treatment groups of one or more EDSS grades at 4 weeks.
                There were no significant differences between the two groups at any stage of the study in any measurement taken: the mean difference in EDSS at 4 weeks (adjusted for baseline level) was 0.07 grades more in those taking oral steroids (95% CI -0.46 to 0.60). The most optimistic outcome for intravenous therapy is an average benefit of less than half a grade improvement on EDSS over oral treatment.
                Since our study did not show any clear advantage of the intravenous regime we conclude that it is preferable to prescribe oral rather than intravenous steroids for acute relapses in MS for reasons of patient convenience, safety, and cost. There is evidence to support both the use of intravenous methylprednisolone (IVMP) in multiple sclerosis (MS) relapse and physiotherapy in the management of MS, but no studies have investigated the combination of steroids and rehabilitation together.
                To evaluate the benefits of IVMP with planned, comprehensive multidisciplinary team (MDT) care compared to IVMP with standard care.
                In this randomised controlled trial, patients confirmed to have had a definite MS relapse severe enough to warrant IVMP (1 g daily for three days) were randomised to two groups. The control group was managed according to the standard ward routine; the treatment group received planned coordinated multidisciplinary team assessment and treatment. Baseline assessments, including demographics and Expanded Disability Status Scale (EDSS) were carried out on both groups. The primary outcome measures were Guy's Neurological Disability Scale (GNDS), and Amended Motor Club Assessment (AMCA). The secondary measures were the Barthel Index (BI), Human Activity Profile (HAP), and Short Form Item 36 Health Survey (SF-36). All measures have published data on reliability and validity. Measures were administered at one and three months.
                Forty subjects, including 27 females, completed data collection. There were no significant differences between the two groups at baseline. Results showed statistically significant differences in GNDS (p = 0.03), AMCA (p = 0.03), HAPM (p < 0.01), HAPA (p = 0.02), and BI (p = 0.02) at three months in favour of planned MDT care.
                This study indicates that combining steroids with planned MDT care is superior to administering them in a standard neurology or day ward setting. Further research is necessary in order to confirm this finding. A randomised double-blind placebo-controlled trial of intravenous methylprednisolone versus oral methylprednisolone at equivalent high dose was carried out on 35 patients with an acute relapse of multiple sclerosis (MS). After baseline evaluation each was randomly allocated to oral treatment and intravenous placebo or intravenous treatment and oral placebo, receiving 500 mg of methylprednisolone for five consecutive days and with reassessment at days five and twenty-eight. There was no significant difference in response when disability or functional scores were compared in the two groups. Adverse effects were minor and equally distributed. In this study oral treatment with methylprednisolone was as effective as intravenous treatment in acute relapse of MS. Ninety-eight patients with multiple sclerosis (MS) in the chronic progression phase entered a 3-year clinical trial to determine if azathioprine (AZ) alone or with adrenal cortical steroids stabilizes the course of MS. In group AM, the patients took AZ throughout and methylprednisolone (MP) for the first 36 weeks. Group AP received AZ and placebo instead of MP. Group PP took placebos for both drugs. We adjusted the AZ to maintain the total white blood cell count within 3,000 to 4,000/mm3; we gave the MP in a fixed dose "pulse" and alternate-day regimen. The "intent-to-treat" groups had no statistically significant differences in the rates of progression among the 3 treatments. Subgroup analysis suggests that patients in the AM group who completed treatment exactly according to protocol did statistically significantly better than the placebo recipients using the sum of Standard Neurological Examination scores, slightly better using the quantitative neuro-performance tests, but no better using Mickey's Illness Severity Scores or Kurtzke's Disability Status Scale. Also, the AZ-treated groups had half the relapse rate of the placebo-treated group. Adverse reactions to AZ accounted for most withdrawals. Hematologic and hepatic abnormalities were significantly associated with AZ, but serious non-MS abnormalities were uncommon and were equally distributed among the 3 groups. Addition of MP to the AZ slightly improved the efficacy of the treatment, but also increased the adverse effects. The benefits of AZ with or without steroids did not outweigh the risks, and therefore we do not recommend this treatment for patients with chronic progressive MS.
The analysis of the five included trials comparing intravenous versus oral steroid therapy for MS relapses do not demonstrate any significant differences in clinical (benefits and adverse events), radiological or pharmacological outcomes. Based on the evidence, oral steroid therapy may be a practical and effective alternative to intravenous steroid therapy in the treatment of MS relapses.