ARTICLE IN BRIEF
Investigators reported that oral steroids were not inferior to intravenously-administered steroids for reducing multiple sclerosis relapses.
A small but well-designed randomized clinical trial indicates that multiple sclerosis (MS) patients who are experiencing a relapse can fare just as well by taking high-dose oral methylprednisolone as they would by getting the steroid intravenously.
Many physicians administer steroids intravenously for MS relapses, in part because high doses of oral drugs can cause gastrointestinal problems.
The new study, conducted in Spain, used clinical assessments of patient disability and findings from magnetic resonance imaging (MRI) brain scans to conclude that oral steroids provide the same treatment benefits as high-dose IV steroids for MS patients in relapse. In addition, the high-dose oral steroid was well tolerated by study participants.
“We have been using the oral route for some time now and we already had the impression that we were gaining good results. With this trial we have been able to demonstrate that objectively,” the lead study author Cristina Ramo-Tello, MD, PhD, told Neurology Today.
Dr. Ramo-Tello, a neurologist at Hospital Germans Trias i Pujol in Badalona, Spain, said the benefits of oral steroids go beyond favorable treatment effects.
“The oral route is less invasive and more convenient than the intravenous route. Patients can take the treatment at home and do not have to travel to a medical facility to have it administered,” she wrote in an e-mail to Neurology Today. “There is less interference with their work and social life. Moreover, the costs for the health system as a whole are significantly reduced.”
The authors of the study, which was published in the June edition of Multiple Sclerosis Journal, noted that “several studies have consistently demonstrated that steroids improve clinical recovery and reduce brain magnetic resonance imaging (MRI) activity,” when MS patients have a relapse. “The therapeutic window and the optimal choice of drug, dose, frequency, treatment duration and administration route remain uncertain.”
The study, which was conducted at seven MS units in the Catalonia region of Spain, included 49 adult MS patients who met the 2005 McDonald criteria for relapsing-remitting MS and experienced a moderate to severe relapse within the previous 15 days. Their Expanded Disability Status Scale (EDSS) score prior to relapse was in the range of 0 (normal neurological exam) to 5 (able to walk short distances without help, but daily activities impaired). Participants were randomly assigned to one of two treatment arms: IV methylprednisolone (1,000 mg a day for three days) and oral placebo; or an oral 1250-mg dose of methlyprednisolone (12 100-mg capsules and one 50-mg capsule each day for three days) and an IV placebo. The high-dose pills had to be specially formulated for the study.
Clinical visits to evaluate the patients for an EDSS score were held at baseline and at one, four, and 12 weeks after the first treatment dose. Brain MRI scans were done at baseline at one and four weeks.
The primary outcome was an improvement on the EDSS score at four weeks. The researchers statistically designed the trial to be a “noninferiority study” of the oral steroid, and they defined improvement as a reduction of at least one point on the EDSS score. The brain MRI scans were evaluated for the number and volume of T2 lesions and the number of gadolinium enhancement (Gd+) T1 lesions.
The researchers reported that 46 percent of patients who got the oral steroid and 39 percent who received the IV at one week improved by at least one point on the EDSS score; at four weeks, that was true for 68 percent and 65 percent respectively of the patients; at 12 weeks, 73 percent and 70 percent respectively improved.
There were no differences between the two groups on MRI as measured by the number of Gd+ T1 lesions or the number and volume of T2 lesions.
“This study provides evidence that oMP [oral methylprednisolone] is not inferior to ivMP [intravenous methylprednisolone] in reducing EDSS and MRI lesions at four weeks for MS relapses and is equally well tolerated and safe,” the researchers concluded.
The most commonly reported side effects were headache, mood disorder, and insomnia. Other side effects included a metallic taste in the mouth, nausea, stomach pain, diarrhea, rash, edema and palpations. The GI complications that many physicians fear did not happen.
The researchers noted that the clinical trial had limitations. It was fairly small, and the period of clinical and radiological follow-up was relatively short. They said differences between oral and IV steroids may have emerged over time. They said that stricter criteria of less than a one-point improvement on the EDSS could have led to a difference between the two groups.
While some physicians have already begun moving toward the use of oral steroids to treat moderate to severe MS relapses, most still rely on IV administration for high doses.
David Mattson, MD, a professor of neurology at Indiana University School of Medicine and director of the Neuroimmunology/Multiple Sclerosis Program, said he uses low-dose oral corticosteroids for mild relapses but tends to use high-dose IV when the symptoms are more disabling or for optic neuritis.
“I don't know why I as an individual practitioner and the medical community in general have not switched,” Dr. Mattson told Neurology Today, though habit and lingering concerns about tolerability factor in.
“In general, people have been skittish about doing high doses of oral corticosteroids because they worry about GI complications in particular,” Dr. Mattson said, but he agreed that the results from this latest study do not support that worry. He said that “it would be much cheaper to do three days to five days of high-dose oral corticosteroids and much more convenient for the patients.”
Jeffrey A. Cohen, MD, a professor of medicine (neurology) and director of the Mellen Center for MS Treatment and Research at Cleveland Clinic, said the study from Spain is “the most rigorous assessment yet of whether oral and intravenous steroids are equivalent” in treating MS relapses.
He cautioned, however, that the study was statistically designed to show that oral steroids are not inferior to the IV version, as opposed to determining whether IV steroids were better. He said that a more stringent definition by the researchers of what was considered “noninferior” could have led to a different result.
Still, all things being fairly equal, it's hard to make a case for using IV steroids,” said Dr. Cohen, who said he tends to fall in about the 50–50 range.
“Right now the decision is somewhat arbitrary, but I think the trend over time is going to be to use high-dose oral steroids,” to treat relapses, though he said the ultimate goal needs to be good management of MS to prevent relapses from occurring in the first place.
Brian Weinshenker, MD, a professor of neurology at Mayo Clinic in Rochester, MN, said the debate over oral versus IV is a worthwhile one because corticosteroids are considered standard treatment for MS attacks.
“If a patient has a disabling attack we know we can speed up their recovery substantially by giving steroids,” he said, though “we don't think it does much in terms of preventing further relapses.”
Dr. Weinshenker said that “making commonly used treatments more acceptable and less expensive are laudable goals.” But he noted that comparative studies of different ways of administering steroids are difficult to conduct and statistically power because “most patients recover no matter what you do,” even with no treatment at all.
“Non-inferiority studies, such as the Spanish study, are difficult to interpret for this reason,” he said.
Dr. Weinshenker said previous research has indicated that there may be a subset of MS patients with severe attacks of MS who might be better off with steroid treatment than without it and possibly with IV treatment instead of oral.
“Post-hoc analysis of the Optic Neuritis Treatment Trial data suggested oral steroids might be associated with a higher frequency of relapse, which curtailed the use of oral steroids for the past decade, at last in lower doses than studied in the Spanish study.”
He said the findings from the new study, along with those from other studies that established the safety of high-dose oral steroids, “might reassure clinicians who want to consider this approach to treating MS attacks.”
EXPERTS: ON ORAL VS. IV STEROIDS FOR MS