Print this page

Immunoglobulins

Immunoglobulins (Igs) are the natural antibodies made in humans by certain immune system cells in response to infection or a foreign substance. Human Igs have been extracted from plasma and pooled, and used IV to treat several conditions. High dose IVIgs have been used to treat conditions including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and MS. Because they are a natural human product they are virtually free of side-effects, and so offer advantages over some other therapies which affect the immune system. With human products, there is always the minor risk of transmission of infectious agents through the serum.
A large RCT by the Austrian Immunoglobulin in Multiple Sclerosis Study Group published in 1997 looked at a monthly dose of IVIg for two years compared with inactive placebo.1 148 patients with relapsing-remitting MS were enrolled in the study. Results showed that the disability score decreased significantly in the treated group, and got worse in the placebo group, and there was a 59 per cent reduction in the number of relapses in the treated group. Best of all, there were no adverse effects. A Danish study of 26 patients looked at MRI lesions during IVIg treatment.2 There were fewer new MRI lesions with IVIg than on placebo (0.4 versus 1.3). The p value was 0.03. During IVIg treatment, fifteen patients had no relapses compared with only seven on placebo (p = 0.02). Although the study was small, this was useful confirmatory evidence of the Austrian study.

A 2004 study of 91 Israeli people early after an attack suggestive of MS reported the results of treating with IVIgs every six weeks.3 The researchers showed that those treated were only one third as likely as people not treated to progress to definite MS within a year. Further, they had fewer lesions on MRI. There were no significant side effects with the treatment.

Another study from Iran combined IVIg and an immunosuppressant drug called azathioprine.4 Although the study was not an RCT, it followed 38 patients with relapsing-remitting MS for three years of this combined therapy. Before starting therapy, patients had been having an average of 1.7 relapses a year. This fell to none by the end of the study, and the disability scale score improved overall.

There has been speculation that some of the benefits seen with IVIgs may be caused not only by immune system effects, but by improved re-myelination of MS lesions. Certainly, at present, the mechanism by which IVIg works is unclear. Nevertheless, the studies show a significant reduction in relapse rates, and improvements in disability scores. Given the low toxicity of this therapy, it makes a very worthwhile addition to our expanding list of agents which can be used for MS when the disease is very active or severe.

However, a large Dutch study of 318 patients with secondary progressive disease found no clinical benefit from IVIgs.5 There was also no decrease in standard MRI measures of disease progression.6 A 2005 summary of published work on IVIgs concluded that they are a second-line treatment in relapsing-remitting MS when other treatments are not available, that they have no role in progressive MS or acute attacks, but that they may be useful after childbirth to prevent relapses, and can delay the onset of definite MS after a first attack.7Side-effects have been documented. These include fever, chills, fatigue, joint and muscle pain, abdominal pain and headache. Serious side-effects have included seizures, heart failure, and kidney failure, but they have been rare. A 2006 Israeli report on the long term side effects of IVIg therapy reported 293 people with MS treated for up to 10 years.8 The authors showed that the therapy was safe even when given over long periods.

More recently, a large placebo-controlled study in people with primary and secondary progressive MS showed a significant benefit for IVIgs in primary, but not secondary, progressive MS.9 Given how few effective treatments there are for primary progressive MS, this should be investigated further, and offered to people who are deteriorating with this type of MS.
Back to Top

  1. Fazekas F, Deisenhammer F, Strasser-Fuchs S, et al. Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Austrian Immunoglobulin in Multiple Sclerosis Study Group. Lancet 1997; 349:589-593.
  2. Sorensen PS, Wanscher B, Jensen CV, et al. Intravenous immunoglobulin G reduces MRI activity in relapsing multiple sclerosis. Neurology 1998; 50:1273-1281.
  3. Achiron A, Kishner I, Sarova-Pinhas I, et al. Intravenous immunoglobulin treatment following the first demyelinating event suggestive of multiple sclerosis: a randomized, double-blind, placebo-controlled trial. Arch Neurol 2004; 61:1515-1520.
  4. Kalanie H, Tabatabaii SS. Combined immunoglobulin and azathioprine in multiple sclerosis. Eur Neurol 1998; 39:178-181.
  5. Hommes OR, Sorensen PS, Fazekas F, et al. Intravenous immunoglobulin in secondary progressive multiple sclerosis: randomised placebo-controlled trial. Lancet 2004; 364:1149-1156
  6. Fazekas F, Sorensen PS, Filippi M, et al. MRI results from the European Study on Intravenous immunoglobulin in Secondary Progressive Multiple Sclerosis (ESIMS). Mult Scler 2005; 11:433-440
  7. Stangel M, Gold R. [High-dose intravenous immunoglobulins in the treatment of multiple sclerosis An update.]. Nervenarzt 2005
  8. Katz U, Kishner I, Magalashvili D, et al. Long term safety of IVIg therapy in multiple sclerosis: 10 years experience. Autoimmunity 2006; 39:513-517
  9. Pohlau D, Przuntek H, Sailer M, et al. Intravenous immunoglobulin in primary and secondary chronic progressive multiple sclerosis: a randomized placebo controlled multicentre study. Mult Scler 2007; 13:1107-1117