IVIG/SCIG Treatment in Patients with Primary Immunodeficiency Diseases

Filiz SADİ AYKANa
aNecmettin Erbakan University Faculty of Medicine, Department of Internal Medicine, Division of Immunology and Allergy Diseases, Konya, Türkiye

Sadi Aykan F. IVIG/SCIG treatment in patients with primary immunodeficiency diseases. Çölkesen F, ed. Primary Immunodeficiency Diseases in Adults. 1st ed. Ankara: Türkiye Klinikleri; 2024. p.105-14.

ABSTRACT
Human immunoglobulin preparations form the basis of human therapy in patients with primary immunodeficiency (PID) in whom the humoral immune system is affected. This immunoglobulin is produced from large plasma pools from 15.000-60.000 individuals. Immunoglobulin replacement therapy (IgRT) helps prevent bacterial severe infections and long-term infection-related complications, especially lung disease, in PID patients. The starting dose is 400-600 mg/kg every four weeks. Stabilization takes up to 3 months. Dosage adjustment should be based on clinical condition and steady-state levels for IgG trough for intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG). Higher IgG trough levels (>800-1000 mg/dL) may be required in selected patients, especially those with chronic lung disease. Differences in product composition and manufacturing may lead to individual side effects and tolerability variations. Therefore, IVIG products should not be used interchangeably. Mild adverse reactions related to the infusion rate are frequently seen with IVIG. Serious systemic adverse events such as renal failure, thromboembolic events and hemolysis are rare and even less frequent with SCIG. SCIG has fewer systemic adverse reactions, while local site reactions are more frequent. After initiating IgRT, follow-up evaluation is recommended every 3-4 months for the first year and every 6-12 months after that. At follow-up, the tolerability and efficacy of treatment should be reviewed and trough or steady-state serum IgG levels should be measured.

Keywords: Primary immunodeficiency; intravenous immunoglobulin; subcutaneous immunoglobulin; advers reaction

Referanslar

  1. Perez EE, Orange JS, Bonilla F, Chinen J, Chinn IK, Dorsey M, et al. Update on the use of immunoglobulin in human disease: A review of evidence. J Allergy Clin Immunol. 2017;139(3S):S1-S46. [Crossref]  [PubMed]
  2. Ammann AJ, Ashman RF, Buckley RH, Hardie WR, Krantmann HJ, Nelson J, et al. Use of intravenous gamma-globulin in antibody immunodeficiency: results of a multicenter controlled trial. Clin Immunol Immunopathol. 1982;22(1):60-7. [Crossref]  [PubMed]
  3. Buckley RH, Schiff RI. The use of intravenous immune globulin in immunodeficiency diseases. N Engl J Med. 1991;325(2):110-7. [Crossref]  [PubMed]
  4. Stiehm ER, Orange JS, Ballow M, Lehman H. Therapeutic use of immunoglobulins. Adv Pediatr. 2010;57(1):185-218. [Crossref]  [PubMed]  [PMC]
  5. Quartier P, Debré M, De Blic J, de Sauverzac R, Sayegh N, Jabado N, et al. Early and prolonged intravenous immunoglobulin replacement therapy in childhood agammaglobulinemia: a retrospective survey of 31 patients. J Pediatr. 1999;134(5):589-96. [Crossref]  [PubMed]
  6. Lederman HM, Winkelstein JA. X-linked agammaglobulinemia: an analysis of 96 patients. Medicine (Baltimore). 1985;64(3):145-56. [Crossref]
  7. Liese JG, Wintergerst U, Tympner KD, Belohradsky BH. High- vs low-dose immunoglobulin therapy in the long-term treatment of X-linked agammaglobulinemia. Am J Dis Child. 1992;146(3):335-9. [Crossref]  [PubMed]
  8. Buckley RH. B-cell function in severe combined immunodeficiency after stem cell or gene therapy: a review. J Allergy Clin Immunol. 2010;125(4):790-7. [Crossref]  [PubMed]  [PMC]
  9. Serana F, Sottini A, Chiarini M, Zanotti C, Ghidini C, Lanfranchi A, et al. The different extent of B and T cell immune reconstitution after hematopoietic stem cell transplantation and enzyme replacement therapies in SCID patients with adenosine deaminase deficiency. J Immunol. 2010;185(12):7713-22. [Crossref]  [PubMed]
  10. Cunningham-Rundles C, Siegal FP, Smithwick EM, Lion-Boulé A, Cunningham-Rundles S, O'Malley J, et al. Efficacy of intravenous immunoglobulin in primary humoral immunodeficiency disease. Ann Intern Med. 1984;101(4):435-9. [Crossref]  [PubMed]
  11. Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92(1):34-48. [Crossref]  [PubMed]
  12. Winkelstein JA, Marino MC, Ochs H, Fuleihan R, Scholl PR, Geha R, et al. The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients. Medicine (Baltimore). 2003;82(6):373-84. [Crossref]  [PubMed]
  13. Bonilla FA, Bernstein IL, Khan DA, Ballas ZK, Chinen J, Frank MM, et al.; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol. 2005;94(5 Suppl 1):S1-63. Erratum in: Ann Allergy Asthma Immunol. 2006;96(3):504. [Crossref]  [PubMed]
  14. Orange JS, Ballow M, Stiehm ER, Ballas ZK, Chinen J, De La Morena M, et al. Use and interpretation of diagnostic vaccination in primary immunodeficiency: a working group report of the Basic and Clinical Immunology Interest Section of the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2012;130(3 Suppl):S1-24. [Crossref]  [PubMed]
  15. Schroeder HW Jr, Dougherty CJ. Review of intravenous immunoglobulin replacement therapy trials for primary humoral immunodeficiency patients. Infection. 2012;40(6):601-11. [Crossref]  [PubMed]  [PMC]
  16. Dorsey MJ, Orange JS. Impaired specific antibody response and increased B-cell population in transient hypogammaglobulinemia of infancy. Ann Allergy Asthma Immunol. 2006;97(5):590-5. Erratum in: Ann Allergy Asthma Immunol. 2006;97(6):819. [Crossref]  [PubMed]
  17. Kaplan B, Kopyltsova Y, Khokhar A, Lam F, Bonagura V. Rituximab and immune deficiency: case series and review of the literature. J Allergy Clin Immunol Pract. 2014;2(5):594-600. [Crossref]  [PubMed]
  18. Al-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, Cunningham-Rundles C, et al. Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency. Front Immunol. 2014;5:162. Erratum in: Front Immunol. 2014;5:460. [Crossref]  [PubMed]
  19. Barlan IB, Geha RS, Schneider LC. Therapy for patients with recurrent infections and low serum IgG3 levels. J Allergy Clin Immunol. 1993;92(2):353-5. [Crossref]  [PubMed]
  20. Litzman J, Jones A, Hann I, Chapel H, Strobel S, Morgan G. Intravenous immunoglobulin, splenectomy, and antibiotic prophylaxis in Wiskott-Aldrich syndrome. Arch Dis Child. 1996;75(5):436-9. [Crossref]  [PubMed]  [PMC]
  21. Bonagura VR. Using intravenous immunoglobulin (IVIG) to treat patients with primary immune deficiency disease. J Clin Immunol. 2013;33 Suppl 2:S90-4. [Crossref]  [PubMed]
  22. Berger M. Subcutaneous administration of IgG. Immunol Allergy Clin North Am. 2008;28(4):779-802, viii. [Crossref]  [PubMed]
  23. Peter JG, Chapel H. Immunoglobulin replacement therapy for primary immunodeficiencies. Immunotherapy. 2014;6(7):853-69. [Crossref]  [PubMed]
  24. Kaveri SV. Intravenous immunoglobulin: exploiting the potential of natural antibodies. Autoimmun Rev. 2012;11(11):792-4. [Crossref]  [PubMed]
  25. Wasserman RL. Progress in gammaglobulin therapy for immunodeficiency: from subcutaneous to intravenous infusions and back again. J Clin Immunol. 2012;32(6):1153-64. [Crossref]  [PubMed]
  26. Hoefferer L, Glauser I, Gaida A, Willimann K, Marques Antunes A, Siani B, et al. Isoagglutinin reduction by a dedicated immunoaffinity chromatography step in the manufacturing process of human immunoglobulin products. Transfusion. 2015;55 Suppl 2:S117-21. [Crossref]
  27. Sriaroon P, Ballow M. Immunoglobulin Replacement Therapy for Primary Immunodeficiency. Immunol Allergy Clin North Am. 2015;35(4):713-30. [Crossref]  [PubMed]
  28. Hernandez-Trujillo HS, Chapel H, Lo Re V 3rd, Notarangelo LD, Gathmann B, Grimbacher B, et al. Comparison of American and European practices in the management of patients with primary immunodeficiencies. Clin Exp Immunol. 2012;169(1):57-69. [Crossref]  [PubMed]  [PMC]
  29. Özen AO, Kıykım A, İkicioğulları KA, Metin A, Aytekin C, Aydoğmuş Ç, ve ark. Primer İmmün Yetmezliklerde İmmünoglobulin Replasman Tedavisi: Güncel Durum Raporu 2019. Özen A, Karakoç Aydıner E, editörler. Ankara: Buluş Yayınevi; 2020.
  30. Roifman CM, Schroeder H, Berger M, Sorensen R, Ballow M, Buckley RH, et al. Comparison of the efficacy of IGIV-C, 10% (caprylate/chromatography) and IGIV-SD, 10% as replacement therapy in primary immune deficiency. A randomized double-blind trial. Int Immunopharmacol. 2003;3(9):1325-33. [Crossref]  [PubMed]
  31. Bonagura VR, Marchlewski R, Cox A, Rosenthal DW. Biologic IgG level in primary immunodeficiency disease: the IgG level that protects against recurrent infection. J Allergy Clin Immunol. 2008;122(1):210-2. [Crossref]  [PubMed]
  32. Quinti I, Soresina A, Guerra A, Rondelli R, Spadaro G, Agostini C, et al.; IPINet Investigators. Effectiveness of immunoglobulin replacement therapy on clinical outcome in patients with primary antibody deficiencies: results from a multicenter prospective cohort study. J Clin Immunol. 2011;31(3):315-22. [Crossref]  [PubMed]
  33. Brennan VM, Salomé-Bentley NJ, Chapel HM; Immunology Nurses Study. Prospective audit of adverse reactions occurring in 459 primary antibody-deficient patients receiving intravenous immunoglobulin. Clin Exp Immunol. 2003;133(2):247-51. [Crossref]  [PubMed]  [PMC]
  34. Pruzanski W, Sussman G, Dorian W, Van T, Ibanez D, Redelmeier D. Relationship of the dose of intravenous gammaglobulin to the prevention of infections in adults with common variable immunodeficiency. Inflammation. 1996;20(4):353-9. [Crossref]  [PubMed]
  35. Misbah SA. Effective dosing strategies for therapeutic immunoglobulin: managing wear-off effects in antibody replacement to immunomodulation. Clin Exp Immunol. 2014;178 Suppl 1(Suppl 1):70-1. [Crossref]  [PubMed]  [PMC]
  36. Immune Deficiency Foundation. Immune Deficiency Foundation Patient Survey. [Link]
  37. Burks AW, Sampson HA, Buckley RH. Anaphylactic reactions after gamma globulin administration in patients with hypogammaglobulinemia. Detection of IgE antibodies to IgA. N Engl J Med. 1986;314(9):560-4. [Crossref]  [PubMed]
  38. Bonilla FA. Intravenous immunoglobulin: adverse reactions and management. J Allergy Clin Immunol. 2008;122(6):1238-9. [Crossref]  [PubMed]
  39. Brown HC, Ballas ZK. Acute thromboembolic events associated with intravenous immunoglobulin infusion in antibody-deficient patients. J Allergy Clin Immunol. 2003;112(4):797-9. [Crossref]  [PubMed]
  40. Gardulf A, Hammarström L, Smith CI. Home treatment of hypogammaglobulinaemia with subcutaneous gammaglobulin by rapid infusion. Lancet. 1991;338(8760):162-6. [Crossref]  [PubMed]
  41. Abolhassani H, Sadaghiani MS, Aghamohammadi A, Ochs HD, Rezaei N. Home-based subcutaneous immunoglobulin versus hospital-based intravenous immunoglobulin in treatment of primary antibody deficiencies: systematic review and meta analysis. J Clin Immunol. 2012;32(6):1180-92. [Crossref]  [PubMed]
  42. Berger M, Rojavin M, Kiessling P, Zenker O. Pharmacokinetics of subcutaneous immunoglobulin and their use in dosing of replacement therapy in patients with primary immunodeficiencies. Clin Immunol. 2011;139(2):133-41. [Crossref]  [PubMed]
  43. Gardulf A, Nicolay U, Asensio O, Bernatowska E, Böck A, Carvalho BC, et al. Rapid subcutaneous IgG replacement therapy is effective and safe in children and adults with primary immunodeficiencies--a prospective, multi-national study. J Clin Immunol. 2006;26(2):177-85. [Crossref]  [PubMed]
  44. Shapiro RS. Subcutaneous immunoglobulin therapy given by subcutaneous rapid push vs infusion pump: a retrospective analysis. Ann Allergy Asthma Immunol. 2013;111(1):51-5. [Crossref]  [PubMed]
  45. Bonilla FA. Pharmacokinetics of immunoglobulin administered via intravenous or subcutaneous routes. Immunol Allergy Clin North Am. 2008;28(4):803-19, ix. [Crossref]  [PubMed]
  46. Wasserman RL, Melamed I, Stein MR, Gupta S, Puck J, Engl W, et al.; IGSC, 10% with rHuPH20 Study Group. Recombinant human hyaluronidase-facilitated subcutaneous infusion of human immunoglobulins for primary immunodeficiency. J Allergy Clin Immunol. 2012;130(4):951-7.e11. [Crossref]  [PubMed]
  47. Stein MR, Koterba A, Rodden L, Berger M. Safety and efficacy of home-based subcutaneous immunoglobulin G in elderly patients with primary immunodeficiency diseases. Postgrad Med. 2011;123(5):186-93. [Crossref]  [PubMed]
  48. Quinti I, Soresina A, Agostini C, Spadaro G, Matucci A, Sfika I, et al. Prospective study on CVID patients with adverse reactions to intravenous or subcutaneous IgG administration. J Clin Immunol. 2008;28(3):263-7. [Crossref]  [PubMed]
  49. Ochs HD, Gupta S, Kiessling P, Nicolay U, Berger M; Subcutaneous IgG Study Group. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases. J Clin Immunol. 2006;26(3):265-73. [Crossref]  [PubMed]
  50. Berger M. Adverse effects of IgG therapy. J Allergy Clin Immunol Pract. 2013;1(6):558-66. [Crossref]  [PubMed]