Review: New advances in the treatment of neurological diseases using high dose intravenous immunoglobulins

Abstract

Since the incidental discovery in 1981 that intravenous immunoglobulins (IVIg) are immunomodulatory, they have been investigated in a large number of putative autoimmune diseases. This has led to licensing for idiopathic thrombocytopenic purpura, Kawasaki disease, and in neurological disorders for Guillain-Barré syndrome (GBS). Although not licensed, randomized controlled trials have also shown IVIg efficacy in other neuroimmunological diseases such as multifocal motor neuropathy (MMN), chronic inflammatory demyelinating neuropathy (CIDP), myasthenia gravis, dermatomyositis, and stiff-person syndrome. However, other indications are currently being explored including Alzheimer's disease, postpolio syndrome, and narcolepsy. There are even reports from experimental studies in stroke. The results of recently published clinical trials in both the classical neuroimmunological disorders as well as for new indications are reported and their role in clinical practice is discussed.

Immunoglobulins for primary or secondary immunodeficiency or for immunomodulation in neurological autoimmune diseases: insights from the prospective SIGNS registry

“…Clinical studies have shown efficacy of high dose intravenous IG (IVIG) in Guillain Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), or multifocal motoric neuropathy (MMN) and provided the basis for regulatory approval of some preparations in these indications (Elovaara et al 2008;Stangel and Gold 2010). In other neurological AID such as myasthenia gravis, dermatomyositis or stiffperson syndrome efficacy of intravenous IG has been shown in controlled studies, but agents are used as second line, in case of non-response to other immunotherapeutics or intolerability to these drugs (Gold et al 2007;Stangel 2008).…”

Clinical applications of immunoglobulin in neuromuscular diseases: focus on inflammatory myopathies

“…However, it is not established the advantage of one method instead of the other in cases of recurrence or no response if another course should be given or plasma exchange performed 2, 22 . In MMN, it is established in different randomized controlled trials the first-line treatment function of IVIg, using the same initial dose of GBS, irrespective of the presence of positivity for anti-GM1 ganglioside antibody or conduction block 2, 22 . Refractory cases or partial responses are indicative of the possible use of immunomodulatory drugs.…”

“…Among all peripheral neuropathy and polyradiculoneuropathy, most studies with promising and positive results with immunoglobulin involved patients with multifocal motor neuropathy (MMN), Guillain-Barré syndrome (GBS) and variants, and CIDP. In CIDP with moderate to severe motor disability, IVIg is proven as the first-line immunotherapy, including for maintenance treatment associated with immunomodulatory drugs 2, 13,22 . In GBS, similarly to the observed effect of plasma exchange therapy, equal responses and effects are observed with IVIg in the standard classical dose of 400 mg/kg per day for 5 days.…”

“…cases without response to steroid immunosupressive treatment 2 . In sporadic inclusion body myositis, it has been proved that cases with severe dysphagia could benefit from intravenous immunoglobulin, even though a formal recommendation is still needed 2,22,30,31,32 . Although clinical response was noticed in the cases described, molecular immune mechanisms, activated immune cells and hystopathological muscle changes were still equally represented before and after immunoglobulin therapy 33 .…”

“…The same results were less pronounced and evinced for polymyositis, in which few studies showed the importance for reduction of corticosteroid dosage in chronic refractory disease, especially in Table 3. Major groups of neurological diseases for which intravenous immunoglobulin has been studied in clinical trials, case reports and currently used in practice 2,18,21,22,23,24,25,26 . cases without response to steroid immunosupressive treatment 2 .…”