Intravenous immunoglobulin (IVIG) is pooled human IgG that is presumed to alter the immune system by various mechanisms. Whereas some smaller studies initially failed to reveal clear evidence of efficacy, an Austrian multicentre study provided evidence that monthly-administered, low-dose IVIG is effective and well tolerated. A group of 148 patients with RRMS (EDSS 1–6) were randomised to receive monthly doses of IVIG (0.15–0.20 g/kg) or placebo for two years. Primary outcome measures were the effect of treatment on clinical disability, measured by the change in EDSS, and the proportion of patients with improved, stable, or worse disability (at least 1 point on the EDSS scale). Intent-to-treat analysis showed that IVIG had a significant, albeit small, beneficial effect on the EDSS end points. In addition, it reduced relapse rates by about half without having an apparent effect on relapse severity. However, it is possible that blinding was not optimal, and this may have biased the study results. Unfortunately, MRI examinations were not obtained in this study and no data on three-month or six-month “confirmed” EDSS changes were presented.

In another study, involving 26 patients, an effect of higher doses of IVIG (2.0 g/kg monthly for six months) on MRI activity could be established, but in this study there were a high number of drop-outs because of adverse events.

In an Israeli double-blind study of 40 patients with RRMS, people were randomly assigned to receive a loading dose of IVIG (0.4 mg/kg/day for 5 days), followed by single boosters (0.4 mg/kg) or placebo once every two months for two years. Annual exacerbation rate was reduced by about 40 percent and there was an effect on EDSS scores. However, total lesion score on brain MRI did not show a significant difference between groups.

A phase three trial of IVIG in 318 patients with SPMS did not show any clinical benefit on relapse rate or disability progression.

Severe side-effects of treatment with IVIG are uncommon, but can include thromboembolism, aseptic meningitis, renal failure, viral infection, eczema, and anaphylaxis. Another potential problem associated with the use of IVIG is that a number of studies have shown that the constituents present in commercially available IVIG preparations can be quite variable.

In addition to having immunoregulatory capacity (by suppressing production of pro-inflammatory cytokines or by containing anti-idiotypic antibodies), some studies suggest that IVIG might be able to promote remyelination. However, small clinical studies performed at the Mayo Clinic do not support the hypothesis that IVIG might be effective in reversing long-standing neurologic and visual deficits.

In the opinion of the Committee, the results of the studies that have been published are controversial. Results of further studies should be awaited before a clear recommendation can be made. Therefore, routine use of IVIG is not currently advised.