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Off-Label Use of Intravenous Immunoglobulin for Neurological Conditions: A Review of Clinical Effectiveness

Last updated: March 14, 2018
Project Number: RC0962-000
Product Line: Rapid Response
Research Type: Drug
Report Type: Summary with Critical Appraisal
Result type: Report


  1. What is the clinical effectiveness of the off-label use of intravenous immunoglobulin for the treatment of neurological or neuromuscular conditions?

Key Message

Sixteen systematic reviews (SRs; five with meta-analyses) and eight randomized controlled trials were identified regarding the clinical effectiveness of off-label use of intravenous immunoglobulin (IVIG) for the treatment of neurological or neuromuscular conditions. There were mixed results regarding the impact of IVIG on epilepsy (from four SRs) and chronic inflammatory demyelinating polyneuropathy (from three SRs). In addition, there was insufficient evidence from three SRs to assess the effectiveness of IVIG in acute disseminated encephalomyelitis, and insufficient evidence from one SR to comment on the effectiveness of IVIG for the treatment of IgM anti-MAG paraprotein-associated demyelinating peripheral neuropathy.IVIG was reported to be no better than placebo or plasma exchange for the treatment of myasthenia gravis in three SRs, while one SR concluded that IVIG may improve response in patients with myasthenia gravis. For patients with encephalitis, one meta-analysis showed no difference between IVIG and placebo for disability outcomes or adverse events, and three other SRs did not find sufficient evidence of an effect after treatment with IVIG to provide strong conclusions. IVIG was no better than placebo for Alzheimer’s Disease, but was associated with fewer adverse events. IVIG was also no better than placebo for postpolio syndrome and reporting of adverse events was lacking. For patients with Rasmussen Syndrome, one SR did not identify sufficient data regarding IVIG use, and another SR found that IVIG was no better than tacrolimus for the treatment of this condition.Evidence from three SRs suggested that IVIG may be better than plasma exchange for the treatment of pediatric Guillain-Barré Syndrome; however, one SR suggested that plasma exchange resulted in better outcomes than IVIG for children with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections. One SR suggested that some immunosuppressant agents (rituximab, mycofenolate) were better than IVIG for neuromyelitis optica, while others (mitoxantrone, cyclophosphamide, natalizumab) were better than IVIG in pediatric multiple sclerosis. However, IVIG was shown to be more effective than placebo for the treatment of multiple sclerosis in adults, while another SR found insufficient data comparing IVIG with placebo for the treatment of neuromyelitis optica to make a strong conclusion regarding its effectiveness.While several studies concluded that off-label IVIG treatments of neurological or neuromuscular conditions may be promising compared with placebo or alternative treatments, many of the identified studies on were at high risk of bias due to rarity of disease (or outcome), small sample size (low power), open-label design, short follow-up, high involvement of industry, and lack of protocol registration. Therefore, results should be interpreted with caution. Additional high quality data from larger, long-term studies are required to make stronger conclusions.