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An Overview of Intravenous and Subcutaneous Immunoglobulin (IVIG/SCIG) In Immunology

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IVIG and SCIG are pinnacle therapies for the treatment of primary humoral immunodeficiencies and are gaining utility across the scope of immunology.

Immunoglobulin may be used to increase serum IgG, modulate the immune system, and help prevent recurrent infections.1 Depending on the specific indication, immunoglobulin therapy may be FDA approved or used off-label with recommendations from clinical guidelines.

Indications with FDA approval for IVIG2

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Indications with off-label use for IVIG

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Monitoring

Monitoring for IVIG patients typically includes:

  • Blood pressure before, during and after the infusion2
    • - IVIG may cause hypotension or hypertension
  • Renal function3
    • - Monitor before initiating therapy, and then at appropriate intervals.
    - IVIG has a US boxed warning for renal dysfunction.
  • IgG concentrations2,11,12
    • - Monitor before initiating therapy, and then every 4-6 months. Measure every 2-3 months if switching from IV to SC IG.
    - IgG reference level: 700-1600 mg/dL
    - Goal trough level: >600 mg/dL OR at least as high as the previous trough level from the previous IVIG dose.
  • IgA concentrations2,11
    • - Low levels of IgA may lead to the formation of IgA antibodies.
    - Patients with IgA antibodies are at a greater risk of infusion reactions from IVIG.
    - Use low IgA IVIG for patients with low IgA and monitor closely for infusion reactions.
    - IgA reference level: 70-400 mg/dL
  • Signs of thrombosis2
    • - IVIG has box warning for increased risk of thrombosis.
    - Patients who have difficulties ambulating may be at a greater risk of thrombosis events.
  • Clinical response

The role of subcutaneous immunoglobulin (SCIG)

SCIG offers several benefits for patients who receive immunoglobulin therapy. The primary benefit is convenience, as the patient may be trained to self-administer SCIG or be able to have a caregiver trained to administer at home. Patients who have a busy schedule, live far away from infusion centers or who have transportation barriers may find great freedom in switching from IVIG to SCIG. SCIG produces a less dramatic spike in serum IgG levels which is beneficial in reducing systemic side effects. Additionally, more frequent dosing of SCIG has been shown to produce higher trough levels and patients may experience less variations in clinical response.13

The main limitations of SCIG are increased infusion-site reactions, increased dosing frequency and less opportunity for healthcare monitoring during infusions. For these reasons, SCIG should be reserved for patients whose disease states are well controlled. If patients experience a decrease in therapeutic response while on SCIG, they may need to be switched back to IVIG therapy.

SCIG therapy is currently FDA approved for primary immunodeficiencies.2 Refer to each product’s prescribing information leaflet for dosing guidance.

Final considerations

The use of IVIG and SCIG in immunology is an evolving topic with new research conducted on a regular basis. Consult your institution’s clinical databases to stay up to date with the latest information regarding IVIG in specific indications.

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References

  1. Perez EE, Orange JS, Bonilla F, et al. Update on the use of immunoglobulin in human disease: A review of evidence. J Allergy Clin Immunol. 2017;139(3S):S1-S46. doi:10.1016/j.jaci.2016.09.023 

  2. Lexi-Drugs. [cited 2020 June 23] In Lexicomp Online [Internet]. Hudson, Ohio: Wolters Kluwer Clinical Drug Information, Inc. Available from:Available from: http://online.lexi.com.

  3. Boughton BJ, Jackson N, Lim S, Smith N. Randomized trial of intravenous immunoglobulin prophylaxis for patients with chronic lymphocytic leukaemia and secondary hypogammaglobulinaemia. Clin Lab Haematol. 1995;17(1):75-80.

  4. Chapel HM, Lee M, Hargreaves R, Pamphilon DH, Prentice AG. Randomised trial of intravenous immunoglobulin as prophylaxis against infection in plateau-phase multiple myeloma. The UK Group for Immunoglobulin Replacement Therapy in Multiple Myeloma. Lancet. 1994;343(8905):1059-1063.

  5. Intravenous immunoglobulin for the prevention of infection in chronic lymphocytic leukemia. A randomized, controlled clinical trial. Cooperative Group for the Study of Immunoglobulin in Chronic Lymphocytic Leukemia (CGSIGCLL). N Engl J Med. 1988;319(14):902-907.

  6. Griffiths H, Brennan V, Lea J, Bunch C, Lee M, Chapel H. Crossover study of immunoglobulin replacement therapy in patients with low-grade B-cell tumors. Blood. 1989;73(2):366-368.

  7. Anderson D, Ali K, Blanchette V, et al. Guidelines on the use of intravenous immune globulin for hematologic conditions. Transfus Med Rev. 2007;21(2)(suppl 1):s9-s56

  8. Feasby T, Banwell B, Benstead T, et al. Guidelines on the Use of Intravenous Immune Globulin for Neurologic Conditions. Transfus Med Rev. 2007;21(2)(suppl 1):57-107.

  9. Jahnke L1, Applebaum S, Sherman LA, et al. An evaluation of intravenous immunoglobulin in the treatment of human immunodeficiency virus-associated thrombocytopenia. Transfusion. 1994;34(9):759-764

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