Although there have been previous studies suggesting no difference between oral and IV high-dose steroids in the management of multiple sclerosis (MS) relapses, they have been methodologically flawed and inadequately powered. The authors of the current study sought to address these previous limitations, taking into account the recommendations on methodology made in a 2012 Cochrane review on this subject.
Their study involved 13 centres in France and enrolled adults with relapsing-remitting MS who were randomised to double-blind treatment with oral or IV methylprednisolone (1000mg daily for 3 days), starting within 15 days of the onset of relapse (which had to be preceded by a period of stability of at least 1 month). The primary endpoint of the study – improvement by day 28 – was defined as a decrease of at least one point in most affected score on Kurtzke Functional System Scale [KFSS], without need for retreatment with corticosteroids (a relapse, required for trial entry, was defined as an increase of the same magnitude in one or more scores on KFSS).
In order to determine that oral was non-inferior to IV methylprednisolone in this setting, the lower 90% CI of the difference between the groups had to be no worse than -15%. This predefined criterion was met, as the absolute difference between the groups was 0.5%, and the lower bound of the CI was -9.5%. Side-effects were similar overall; however insomnia was reported more frequently in the oral group (77% v 64% in the IV group; p=0.039).
The authors suggest that their findings could have implications for patient convenience, cost and speed of access to treatment for MS relapses. They do however caution that oral treatment may increase use by non-specialists, without thorough consideration of the indication.
NICE issued a clinical guideline on MS in 2014. This recommends the following in terms of treating a relapse:
• Offer treatment with oral methylprednisolone 0.5g daily for 5 days (lower doses not recommended)
• Consider intravenous methylprednisolone 1g daily for 3–5 days as an alternative for people with MS in whom oral steroids have failed or not been tolerated or who need admitting to hospital for a severe relapse or monitoring of medical or psychological conditions such as diabetes or depression.
• Do not give people with MS a supply of steroids to self-administer at home for future relapses.
The dose of oral MP used in this study is different to that recommended in the NICE guideline, which was published prior to the results of this study being available. In the full version of the guideline, the Guideline Development Group (GDG) notes that the available studies used different doses of steroids (typically 500-1000mg/day for IV and 500mg/day for oral) and that there was no clear evidence on the most effective to use. Specialist opinion was that the standard regimen is 1g intravenous methylprednisolone for 3 days or 500mg oral methylprednisolone for 5 days, regardless of patient weight. The GDG noted two ongoing studies – the current one and another (OMEGA trial) which is evaluating doses of 1400mg/day oral and 1000mg/day IV. Based on the evidence considered, the GDG concluded that oral steroids were appropriate unless the patient was having a severe relapses or when oral steroids have failed or not been tolerated. Oral treatment can be given to patients at home, which may be helpful for patients who are at some distance from specialist care.