Off-Label Use of Intravenous Immunoglobulin (IVIG)

Key Messages

Off-label IVIG for Neurological Conditions:

• Studies suggest that IVIG treatment for neurological conditions is promising, but compelling evidence that IVIG works to improve most neurological conditions is lacking.
• Evidence suggests that IVIG may be better than plasma exchange for the treatment of pediatric Guillain-Barré Syndrome, and IVIG is shown to be more effective than placebo for the treatment of multiple sclerosis in adults.
• IVIG is no better than placebo for Alzheimer disease, encephalitis, or post-polio syndrome.
• The results for epilepsy, myasthenia gravis, and chronic inflammatory demyelinating polyneuropathy are mixed, making it unclear whether or not IVIG is an effective treatment.

Off-label IVIG for Hematological Conditions:

• No evidence was found for aplastic anemia, autoimmune neutropenia, hyperhemolysis after transfusion, and acquired hemophilia.
• A limited amount of evidence was found for blood conditions affecting a fetus or newborn. Overall, the evidence on IVIG for these specific conditions compared with other treatment options was mixed.

Off-label IVIG for Autoimmune or Inflammatory Conditions:

• Evidence indicates that the off-label use of IVIG may be effective in some autoimmune diseases but not in others.
• IVIG improves outcomes for patients with systemic lupus erythematosus, and it improves cardiac outcomes in infants of mothers with antiphospholipid syndrome during pregnancy.
• Limited evidence does not show a benefit with IVIG for dermatomyositis, myasthenia gravis, polymyositis, Kawasaki disease, Sydenham chorea, or cardiac complications of acute rheumatic fever.

Off-label IVIG for Non-neurological Paraneoplastic Disorders:

• No evidence was found, so it is not known whether or not IVIG is effective in treating non-neurological paraneoplastic disorders.

Off-label IVIG for Dermatological Conditions:

• Evidence is scarce and based mainly on non-randomized studies or small randomized controlled studies.
• For Stevens-Johnson syndrome or toxic epidermal necrolysis, IVIG treatment — alone or combined with corticosteroids — did not show survival benefit, but there may be a positive correlation between high-dose IVIG and some clinical benefits.
• For bullous pemphigoid, IVIG reduces the time-to-treatment reduction compared with placebo.
• For polymyositis or dermatomyositis, IVIG with corticosteroids improves muscle strength and the biochemical profile compared with placebo or corticosteroids alone (IVIG alone compared with placebo does not).

Off-label IVIG for Recurrent Spontaneous Abortion:

• Whether IVIG improves the chances of live birth in women who have experienced repeated miscarriage is unclear.
  • Some studies show no difference in live birth rates with IVIG compared with placebo and other treatments.
  • Other studies show a significant improvement in rates of live birth with IVIG compared with no IVIG.
• Studies that included obstetrical, perinatal, and neonatal outcomes found no important differences between groups treated with IVIG and those not treated with IVIG.

Off-label IVIG for Solid Organ Transplant Rejection:

• Limited evidence shows no difference in renal effect with IVIG and rituximab compared with placebo in patients with chronic, antibody-mediated rejection following renal transplant.
• Limited evidence shows an improvement in renal function in patients with chronic, antibody-mediated rejection following renal transplant with IVIG versus methylprednisolone.