Immunoglobulins

Immunoglobulins are the natural antibodies made in humans by certain immune system cells in response to infection or a foreign substance.

Immunoglobulins (Igs) are natural antibodies made in the body by certain immune system cells in response to infection or foreign matter. Human Igs have been extracted from plasma and pooled, and used intravenously 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 multiple sclerosis.

Because they are a natural human product, they are virtually free of side effects and offer advantages over some other therapies that affect the immune system.

With human products, there is always the minor risk of transmission of infectious agents through the serum.

Research on immunoglobins

A large immunoglobulin MS study (published in 1997 by the Austrian Immunoglobulin in Multiple Sclerosis Study Group) offered patients a monthly dose of IVIgs for 2 years, as compared with inactive placebo.  Among the 148 patients with relapsing-remitting MS who enrolled in the study, disability scores decreased significantly in the treated group and got worse in the placebo group. There was a 59% reduction in the number of relapses in the treated group. Best of all, there were no adverse effects.

A Danish study of 26 patients found fewer new MRI lesions with IVIgs than on placebo (0.4 versus 1.3).During the treatment, 15 patients had no relapses compared with only seven on placebo. Although the study was small, this was useful confirmation 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. The researchers showed that those treated were one-third as likely as those not treated to progress to definite MS within a year. Further, they had fewer lesions and no significant side effects.

A study from Iran combined IVIgs and an immunosuppressant drug called azathioprine. The study (which was not a randomized controlled trial) followed 38 patients with relapsing-remitting MS for 3 years of this combined therapy. Before starting IVIgs, patients had been averaging 1.7 relapses a year. This fell to none by the end of the study, and the disability scale scores improved overall.

A 2006 Israeli report on the long-term side effects of IVIgs followed 293 people with MS treated for up to 10 years. The authors showed that the therapy was safe even when given over long periods.

There is speculation that some of the benefits seen with IVIgs may be caused not only by their effects on the immune system, but by improved remyelination of MS lesions. At present, the mechanism by which IVIgs work is unclear. Nevertheless, the studies show significantly reduced relapse rates and improved disability scores. Given their low toxicity, IVIgs are worth considering when MS is very active or severe.

However, a large Dutch study of 318 patients with secondary progressive disease found no clinical benefit from IVIgs. There was also no decrease in standard MRI measures of disease progression. A 2005 summary of published work on IVIgs concluded they:

  • Are a second-line treatment in relapsing-remitting MS when other treatments are unavailable
  • Have no role in progressive MS or acute attacks
  • May be useful after childbirth to prevent relapses
  • Can delay the onset of definite MS after a first attack

Side effects of immunoglobulins

Documented side effects include fever, chills, fatigue, joint and muscle pain, abdominal pain and headache. Serious side effects, which have been rare, include seizures, heart and kidney failure.

More recently, a large placebo-controlled study in people with primary and secondary progressive MS showed significant benefit from IVIgs in primary, but not secondary, progressive MS. 

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.

Unfortunately, they are not licensed for use in MS in most countries outside of Europe.


References

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