Benefit of IVIG for Relapsing Remitting Multiple Sclerosis

Source: Fazekas F, et al. Randomized placebo-controlled trial of monthly intravenous immunoglobulin (IVIG) therapy in relapsing-remitting multiple sclerosis. Lancet 1997;349:589-593.

In this double-blinded study of 150 relapsing remitting multiple sclerosis (RRMS) patients, expanded disability status scale (EDSS) 1-6 (mean, 3.3), 75 patients were treated either with monthly IVIG (0.15-0.2 g/kg) or placebo for two years. The primary outcome measure of clinical disability showed that the IVIG-treated patients had a decrease in their EDSS of -0.23 (95% CI - 0.43 to -0.03) vs. an increase in the placebo group EDSS of 0.12 (95% CI -0.13 to -0.37; P = 0.008). In the IVIG group, the percentage of patients with improved, stable, or worse clinical disability were 31%, 53%, and 16%, respectively, compared with 14%, 63%, and 17% in the placebo group.

Evaluation of secondary outcome measures found fewer confirmed relapses in the IVIG group vs. placebo (62 vs 116) and more relapse-free patients in the treated group (53% vs 36%; P = 0.03).


This is the first large-scale controlled trial of the efficacy of long-term monthly doses of IVIG in the treatment of relapsing remitting MS. The results indicate a modest benefit in improved clinical disability (final EDSS IVIG 3.09 vs placebo 3.49; P = 0.008) and reduced relapse frequency. This intention-to-treat analysis demonstrates effectiveness of IVIG comparable to that seen with interferon or copolymer-1 (see Neuro Alert 1996;10:74-75), although differences in study design make a strict comparison impossible. The benefits of IVIG for a variety of autoimmune or inflammatory, demyelinating disorders of the peripheral nervous system have previously been demonstrated (see pages 75-76). A previous one-year open trial of IVIG in 10 patients with RRMS also showed a reduction in exacerbation rate and disability (Achiron, et al. Arch Neurol 1992;49:123-126).

Given that gadolinium-enhanced brain MRIs have been established as an objective and quantifiable measure of disease activity in MS, it is disappointing that this study did not include serial brain MRIs as a confirmatory index of clinical response. Despite the broad empiric use of IVIG for autoimmune disorders, the mechanism by which IVIG might exert its benefits is unknown. Our experience at the New York Hospital suggests that monthly IVIG (0.4 mg/kg) is a safe adjunctive therapy for RRMS patients with clinical exacerbations and increasing clinical disability who are not adequately controlled by treatment with interferon-beta and IV corticosteroids. Thus, in patients with more severe disease refractory to conventional therapy, IVIG may provide a measure of control of disease activity. The expense of IVIG therapy may cause many insurers to refuse payment. Large-scale use will undoubtedly be restricted by the plethora of managed health care companies, but a cost-benefit analysis of IVIG with other expensive therapies such as interferon-beta deserves evaluation. —ba