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Steroids for Multiple Sclerosis Relapses: Pills or IV?

Alexis A. Lizarraga, MD, MS

Relapses are new or worsening symptoms caused by MS. They can lead to a temporary or permanent increase in disability. Until recently, high doses of intravenous methylprednisolone, a type of steroid, were the standard treatment for relapses in MS. Steroids are thought to work in MS relapse due to their ability to change the immune system. Steroids may help to reduce the active inflammation seen in MS attacks by preventing movement of immune cells from the body’s circulation to the brain and spinal cord areas.

Intravenous (IV) steroids, or steroids administered via a needle placed in the vein, were found to hasten recovery after an MS attack in several placebo-controlled studies. The largest of these clinical trials was the Optic Neuritis Treatment Trial (ONTT) in 1994 which evaluated people with a first episode of optic neuritis, or inflammation of the optic nerve, a typical relapse in people with MS. In the ONTT, subjects were treated with either 3 days of IV methylprednisolone at a dose of 1 gm per day or low-dose oral steroids at a dose of 1 mg of prednisone per kg of body weight for 14 days. This study suggested that subjects receiving this low dose of oral steroids recovered more slowly than those treated with the high dose of IV steroids. Moreover, the study indicated that frequency of relapse was higher in the low dose oral steroid-treated group than those treated with high dose IV steroids.

The ONTT had its limitations, however. The doses of oral steroids were much lower than the doses of IV steroids. Also, subjects with optic neuritis, but not necessarily a diagnosis of MS, were included in the study. Other studies comparing oral and IV steroids had similar problems in design. Nevertheless, these studies provided a rationale for the preference of treatment of MS relapse with high-dose IV steroids rather than oral steroids for the next 20 years.

In 2012, an expert evaluation of several studies concluded that there was not enough evidence to decide whether or not oral steroids are effective for MS relapses, particularly if high-dose oral steroids are used. In 2015, the landmark French COPOUSEP trial “cleared the air”. This study of 200 people with relapsing remitting MS was designed specifically to decide if oral steroids were as effective as IV steroids. In contrast to the ONTT, a similar dose of steroids was administered either orally or intravenously within 2 weeks of onset of relapse symptoms. Both the subjects and examiners did not know which treatment participants received, and subjects were randomly chosen for each group.

The primary outcome studied was to see if disability scores 1 month after treatment were different between subjects treated with equivalent doses of IV versus oral steroids. Results of the trial showed that 81% of people in the oral group and 80% of people in the IV group improved at least one point in their disability score. The results confirmed that oral methylprednisolone at a dose of 1 gm/day for 3 days was not inferior to treatment with the same dose of IV methylprednisolone. Other outcomes examined include recovery at 6 months after treatment and frequency of new relapses for up to 6 months after treatment, which were also similar between the oral group and the IV group. Side effects for each treatment were also compared via questionnaire and were essentially the same, except for a slightly higher risk for insomnia for the oral regimen. The authors recommend taking oral steroids in the morning to avoid insomnia.

These results are very important for MS management. We now have solid evidence that the appropriate dose of steroid pills is just as effective for MS relapse as IV steroids. Advantages of pills include ease of dosing, ability to take the medication in the comfort of home, and excellent and quick availability in pharmacies of oral steroids.

It is important to remember that steroids, either IV or pills, have the potential for side effects. Side effects of steroids include allergic reactions, depression, and mood changes which can include psychosis, insomnia, swelling, headache, increased appetite, increased blood sugar levels, increased blood pressure, lower resistance to infection, stomach irritation or, even rarely, changes in the rhythm of the heart. Treatment with steroids should only be undertaken under the care of a medical professional with expertise in treating MS to ensure that the benefits of steroids outweigh the risks in your particular case. If you are receiving IV steroids and are interested in receiving the medication orally, talk to your provider.