A randomized trial of intravenous immunoglobulin in inflammatory demyelinating optic neuritis

Abstract

Several immunomodulatory agents have been shown to favorably influence the short-term natural history of multiple sclerosis. Corticosteroids may shorten the duration of clinical and magnetic resonance imaging evidence of recent clinical worsening in multiple sclerosis and optic neuritis, but their effect is incomplete and transient. No treatment has been identified to reverse long-standing neurologic dysfunction in demyelinating disease. Remyelination is seen in established multiple sclerosis plaques, raising the possibility that therapeutic intervention could enhance clinical recovery. Studies in animal models of demyelinating disease have shown that administration of immunoglobulin (Ig) induces central nervous system remyelination. The purpose of this study was to determine whether intravenous immunoglobulin (IVIg) reverses chronic visual impairment in multiple sclerosis patients with optic neuritis. In this double blind, placebo-controlled Phase II trial, 55 patients with persistent acuity loss after optic neuritis were randomized to receive either IVIg 0.4 g/kg daily for five days followed by three single infusions monthly for three months, or placebo. The trial was terminated by the National Eye Institute because of negative results when 55 of the planned 60 patients had been enrolled. Fifty-two patients completed the scheduled infusions, and 53 patients completed 12 months of follow-up. Analysis of this data indicated that a difference between treatment groups was not observed for the primary outcome measure, improvement in logMAR visual scores at 6 months (p = 0.766). Exploratory secondary analyses suggested that IVIg treatment was associated with improvement in visual function (including logMAR visual scores at 6 months and visual fields at 6 and 12 months) in patients with clinically stable multiple sclerosis during the trial. The authors conclude that IVIg administration does not reverse persistent visual loss from optic neuritis to a degree that merits general use.—Nancy J. Newman