Intravenous Immunoglobulin Offers New Treatment Opportunities for Neurological Diseases

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Although it is currently used off-label for many neuroinflammatory and neurodegenerative disorders, intravenous immunoglobulin is showing promise for a growing number of neurological diseases.

Because of its anti-inflammatory efficacy in autoimmune conditions, intravenous immunoglobulin (IVIG) is also being investigated for, and has shown efficacy in, the treatment of a growing number of neurological diseases. A new paper published in Neurotherapeutics outlines these emerging data.

IVIG preparations contain antibodies directed against a broad range of pathogens, according to the authors, as well as against numerous foreign and self-antigens. Based on the known heterogeneity of the various autoimmune disease conditions that respond to IVIG, the authors said it seems likely that different disease-specific pathways mediate the clinical efficacy of this agent for a given disease. Because of this, it has been difficult to find a general mechanism for the anti-inflammatory or immunomodulating efficacy of IVIG, according to the study.

In some case series, IVIG has also shown promise in treating various neuroinflammatory, painful, or even neurodegenerative disorders; however, for these diseases, use of IVIG is off label.

Numerous randomized controlled trials have shown that IVIG has efficacy in acute and chronic demyelinating neuropathies, in worsening myasthenia gravis as a short-term therapy, in some inflammatory myopathies, and in stiff-person syndrome. The investigators outlined the potential uses of IVIG in several diseases, including Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), and several other therapeutic areas.

Several randomized trials of GBS have compared the use of IVIG with plasmapheresis. Two trials found that 1 dose of IVIG was comparable to plasmapheresis in outcome measures, including time to unaided walking and discontinuation of ventilation. In GBS variants, such as the acute axonal motor or motor sensory forms, Miller-Fisher syndrome, or acute dysautonomia, IVIG appeared to be helpful, although controlled studies have not been conducted.

In CIDP, controlled studies have found that steroids, plasmapheresis, and IVIG are equally effective on a short-term basis. The ICE trial, the largest ever conducted in CIDP, also found that IVIG is safe and effective in the long term, leading to the first FDA-approved indication for a brand of IVIG.

In practice, the investigators said they have noted that some patients respond predominantly to IVIG, others to prednisone, and others to plasmapheresis. Although the reasons for these differences remain unclear, patients more likely to respond to IVIG appear to have a disease duration of less than 1 year, a relapsing course, and electrophysiological signs of demyelination with conduction block.

Unlike GBS and CIDP, the investigators said MMN does not respond to steroids or plasmapheresis, only to IVIG. Efficacy of IVIG in MMN has been established in a number of controlled trials, resulting in approval of Baxter’s IVIG product for the treatment of MMN. Improvement following treatment typically lasts from 3 to 6 weeks, requiring reinfusion at almost predictable time periods. According to the paper, therapy starts with 2 g/kg but the response can be maintained with 1 g/kg.

Other neuropathies have seen varying results with IVIG. It has been unsuccessful in anti-myelin-associated glycoprotein demyelinating neuropathy based on 2 controlled trials. It has also been anecdotally tried in diabetic amyotrophy, vasculitic neuropathy, and in some painful sensory neuropathies, such as those associated with Sjogren syndrome, all with varying results. At this point, the authors said the evidence of efficacy is insufficient to earn recommendation for use of IVIG in any of these conditions.

REFERENCE

Lunemann J, Quast I, Dalakas M. Efficacy of Intravenous Immunoglobulin in Neurological Diseases. Neurotherapeutics; September 2015. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4720677/. Accessed May 6, 2021.

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