Clinical Question: Does intravenous immunoglobulin delay the development of multiple sclerosis following an initial neurologic event associated with demyelination?
Setting: Outpatient (specialty)
Study Design: Randomized controlled trial (double-blinded)
Synopsis: Patients were eligible for this study if they were between 15 and 50 years of age and had a first well-defined neurologic event consistent with multiple sclerosis that was confirmed by neurologic examination and brain magnetic resonance imaging in the preceding 90 days. They also had to experience complete or partial regression of symptoms.
Patients were assigned randomly (method of allocation concealment not described) to receive a loading dose of 0.4 g per kg intravenous immunoglobulin for five consecutive days followed by 0.4 g per kg once every six weeks for one year (n = 45). The control group received disguised normal saline infusions (n = 46). A neurologist unaware of treatment assignment examined each patient every three months. If a relapse was suspected, two neurologists would independently examine the patient. On confirmation of a relapse by one of the two neurologists, the patient was withdrawn from the study. Relapse was defined as the onset of new neurologic symptoms suggestive of white matter involvement occurring for a period of at least 48 hours and accompanied by objective neurologic findings.
The primary end point, assessed by intention to treat, was defined as the number of patients who experienced a second attack within one year. This criterion establishes the diagnosis of multiple sclerosis. At the end of one year, 26 percent of patients treated with intravenous immunoglobulin developed a second event compared with 50 percent of patients treated with placebo (P = .03). In other words, four patients would need to be treated with intravenous immunoglobulin for one year to delay one patient from developing a second event (95 percent confidence interval, three to 30).
Bottom Line: Over one year, intravenous immunoglobulin delays a second neurologic event consistent with multiple sclerosis in patients presenting with an initial event of demyelination. The effect beyond one year is unknown. (Level of Evidence: 1b)