What is Intravenous Immunoglobulin (IVIG)?

What is Intravenous Immunoglobulin (IVIG)?

IVIG is a biological product comprised of pooled immunoglobulin G (IgG) antibodies harvested from the plasma of thousands of healthy blood donors and prepared for intravenous administration. 1

Composition and Source

• IVIG contains predominantly pooled IgG antibodies extracted from plasma of 1,000+ donors 1, 2
• The product is manufactured from pooled donor plasma, with potentially important differences existing between manufacturers 1
• It contains anti-idiotypic antibodies that can inhibit HLA-specific alloantibodies both in vitro and in vivo 1

Mechanisms of Action

The immunomodulatory mechanisms of IVIG are not fully understood, but multiple pathways have been identified: 1

• Blockade of Fc-γ receptors on leukocytes and endothelial cells 1, 2
• Inhibition of the complement system 1
• Modulation of B- and T-lymphocyte activity and effector functions, impacting antigen presentation 1
• Downregulation of the B-cell receptor 1
• Neutralization of pathogenic autoantibodies and cytokines 1
• Modulation of cytokine and chemokine synthesis and release 2
• Augmentation of regulatory T-cell activity 1
• Suppression of antibody synthesis 1

Clinical Indications

FDA-Approved Uses

• Primary immunodeficiencies (IgG replacement therapy) 3, 4, 5
• Immune thrombocytopenic purpura (ITP) 4, 5
• Kawasaki disease 1, 5
• Bone marrow transplantation in patients aged >20 years 5
• Chronic B-cell lymphocytic leukemia 5
• Pediatric AIDS 5

Off-Label Uses in Autoimmune/Inflammatory Conditions

• Neurologic conditions: Guillain-Barré syndrome, myasthenia gravis, neuropathies 1
• Dermatologic conditions: Pemphigus vulgaris, pemphigoid, blistering disorders 1, 5
• Rheumatologic conditions 1
• Immune hematologic conditions 1
• Transplant-related: Antibody-mediated rejection, desensitization protocols 1
• Immunotherapy-related adverse events (steroid-refractory cases) 1
• Enterovirus radiculoneuropathy in immunosuppressed patients 6

Dosing Regimens

Standard Dosing Protocols

• High-dose therapy: 2 g/kg as a single infusion over 10-12 hours 1
• Alternative regimen: 1-2 g/kg divided over 2-5 days 1, 6
• ITP dosing: 0.4 g/kg daily for 2-5 consecutive days 4
• Immunodeficiency replacement: 0.2-0.3 g/kg monthly 4

Maintenance Therapy

• Treatment may require monthly intervals for sustained effect 1, 6
• Multiple treatments needed if used to maintain remission 1

Adverse Effects

Common Side Effects

• Headache 1, 6
• Chills, rigors, fever, myalgia 1
• Volume overload 1, 6
• Nausea 1

Serious Adverse Effects

• Aseptic meningitis (resolves quickly without neurological sequelae) 1, 6
• Anaphylaxis (particular risk in IgA-deficient patients with IgE anti-IgA antibodies) 1, 6, 3, 4
• Coombs-positive hemolytic anemia (especially in AB blood type individuals) 1

Important Clinical Considerations

Vaccination Timing

• Measles, mumps, and varicella immunizations should be deferred for 11 months after receiving high-dose IVIG 1
• Children at high risk of measles exposure may receive earlier vaccination with re-immunization at least 11 months post-IVIG 1

Monitoring Requirements

• Monitor IgG levels if hypogammaglobulinemia present (target ≥400 mg/dL) 6
• Assess for adverse effects during and after infusion 6
• Blood glucose monitoring during concurrent corticosteroid therapy 1

Contraindications

• Selective IgA deficiency with detectable IgA antibodies 4

Cost Considerations

• IVIG is expensive (cost category: $$$$) 1
• Worldwide shortage of IVIG is predicted, necessitating judicious use 2