Intravenous immunoglobulins as therapeutic option in the treatment of multiple sclerosis

Abstract

Treatment of neurological disorders with intravenous immunoglobulin (IVIG) is an increasing feature of practice for an expanding range of indications. This article reviews the current literature regarding the role of IVIG treatment in multiple sclerosis (MS) and summarizes recommendations for the use of IVIG in different courses and clinical subsets of the disease. Principally based on the results of four randomized, double-blind, placebo-controlled trials (RCTs) and a corresponding meta-analysis, the amount of evidence for the efficacy of IVIG treatment is currently most convincing for the relapsing-remitting course of MS (RRMS); nevertheless, it lags clearly behind that for beta interferon due to smaller study sizes, partial deficits in study design and not established optimal dosage. This prompted the basis for a consensus statement in some countries to recommend IVIG as second-line treatment in RRMS, when other licensed therapies (i. e., beta interferon, glatiramer acetate) are individually not tolerated due to side effects or concomitant disease. Recent evidence indicates that IVIG is also effective in clinically isolated syndrome (CIS) and should be considered as a therapeutic option, particularly when licensed immunotherapy can not be offered. During an acute relapse additional IVIG administration to established steroid treatment showed no benefit. Despite promising experimental data on promotion of remyelination, fixed chronic deficits were not reversed or improved by long-term IVIG treatment either. Currently there is no indication for IVIG treatment in the chronic progressive disease stages, since a large and well-designed RCT failed to show any beneficial effect in patients with secondary progressive MS (SPMS) and data derived from primary progressive MS (PPMS) are still pending. However, preliminary results of a so far unpublished RCT including patients with PPMS and SPMS suggest a strong trend towards a beneficial effect in PPMS. So far, IVIG is the only therapy investigated for reducing postpartum relapses, whereas immunomodulatory drugs are contraindicated during pregnancy and lactation period. Data evaluating the peripartal use of IVIG along with the positive results of the trials in RRMS justify postpartal IVIG treatment particularly for mothers, who choose to breastfeed, under consideration of the recommendations specified for the relapsing-remitting disease course. As recently shown IVIG administration right from the early weeks of pregnancy appears to be a promising strategy, but cannot be recommended from the viewpoint of evidence-based medicine.