Skip to main content

Advertisement

SpringerLink
Log in

Rapid Subcutaneous IgG Replacement Therapy is Effective and Safe in Children and Adults with Primary Immunodeficiencies—A Prospective, Multi-National Study

  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Sixty patients (16 children, 44 adults) participated in the study aiming at evaluating: (i) IgG levels when switching patients from intravenous IgG (IVIG) infusions in hospital to subcutaneous (SCIG) self-infusions at home using the same cumulative monthly dose, (ii) protections against infections, and (iii) safety of a new, ready-to-use 16% IgG preparation. All children and 33 adults had received IVIG therapy for >6 months at enrolment. Ten adults who had been on SCIG therapy for many years served as controls. Mean serum IgG trough levels increased in the pre-IVIG children from 7.8 to 9.2 g/L (non-inferiority: p < 0.001) and in the adults from 8.6 to 8.9 g/L (non-inferiority: p < 0.001). Totally 114 respiratory tract infections occurred, 90% of them mild. One serious bacterial infection (pneumonia) was reported for one adult. The annualized rate of serious infections was 0.04 episodes/patient. In total 2297 infusions were given and 28 (1%) systemic adverse reactions occurred, none of them severe. Local tissue reactions declined over time, this being particularly distinct after 8 to 10 weeks. In conclusion, the SCIG administration route was safe. High IgG levels were easily maintained resulting in a very good protection against infections.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.

Similar content being viewed by others

REFERENCES

  1. Rosen FS, Eibl M, Roifman C, Fischer A, Volanakis J, Aiuti F, Notarangelo L, Kishimoto T, Resnick IB, Hammarström L, Seger R, Chapel H, Cooper MD, Geha RS, Good RA, Waldmann TA, Wedgwood RJP: Primary immunodeficiency diseases. Report of an IUIS Scientific Committee. Clin Exp Immunol 118(Suppl. 1):1–28, 1999

    Google Scholar 

  2. Chapel HM for the Consensus Panel for the diagnosis and management of primary antibody deficiencies: Consensus on diagnosis and management of primary antibody deficiencies. BMJ 308:581–585, 1994

    PubMed  CAS  Google Scholar 

  3. Gardulf A, Hammarström L, Smith CIE: Home treatment of hypogammaglobulinaemia with subcutaneous gammaglobulin by rapid infusion. Lancet 338:162–166, 1991

    Article  PubMed  CAS  Google Scholar 

  4. Gardulf A, Andersen V, Björkander J, Ericson D, Frøland SS, Gustafson R, Hammarström L, Jacobsen MB, Jonsson E, Möller G, Nyström T, Soeberg B, Smith CIE: Subcutaneous immunoglobulin replacement in patients with primary antibody deficiencies: Safety and costs. Lancet 345:365–369, 1995

    Article  PubMed  CAS  Google Scholar 

  5. Thomas MJ, Brennan VM, Chapel HM: Rapid subcutaneous immunoglobulin infusions in children. Lancet 342:1432–1433, 1993

    Article  PubMed  CAS  Google Scholar 

  6. Abrahamsen TG, Sandersen H, Bustnes A: Home therapy with subcutaneous immunoglobulin infusions in children with congenital immunodeficiencies. Pediatrics 98:1127–1131, 1996

    PubMed  CAS  Google Scholar 

  7. Gaspar J, Gerritsen B, Jones A: Immunoglobulin replacement therapy by rapid subcutaneous infusions. Arch Dis Child 79:48–51, 1998

    Article  PubMed  CAS  Google Scholar 

  8. Chapel HM, Spickett GP, Ericson D, Engl W, Eibl M, Björkander J: The comparison of the efficacy and safety of intravenous versus subcutaneous immunoglobulin replacement therapy. J Clin Immunol 20:94–100, 2000

    Article  PubMed  CAS  Google Scholar 

  9. Stiehm ER, Casillas AM, Finkelstein JZ, Gallagher K, Groncy PM, Kobayashi RH, Oleske JM, Roberts RL, Sandberg ET, Wakim ME: Slow subcutaneous human intravenous immunoglobulin in the treatment of antibody immunodeficiencies: Use of an old method with a new product. J Allergy Clin Immunol 101:848–849, 1998

    Article  PubMed  CAS  Google Scholar 

  10. Radinsky S, Bonagura VR: Subcutaneous immunoglobulin infusion as an alternative to intravenous immunoglobulin. J Allergy Clin Immunol 112:630–633, 2003

    Article  PubMed  CAS  Google Scholar 

  11. Duff KA, Roy S, Poll J, Berger M: IgG replacement by the subcutaneous route using preparations licensed in the USA for administration by other routes. J Allergy Clin Immunol 113:S43, 2003

    Article  Google Scholar 

  12. Berger M: Subcutaneous immunoglobulin replacement in primary immunodeficiencies. Clin Immunol 112:1–7, 2004

    Article  PubMed  CAS  Google Scholar 

  13. Gustafson R, Gardulf A, Granert C, Hansen S, Hammarström L: Prophylactic therapy for selective IgA deficiency. Lancet 350:865, 1997

    Article  PubMed  CAS  Google Scholar 

  14. Berger M, Duff K, Poll J, Roy S: IgG replacement by the subcutaneous route using preparations licensed in the US for administration by other routes. In Intravenous immunoglobulins in the third millennium. Proceedings of the 5th International Symposium on IVIG, MC Dalakas, PJ Späth (eds). New York, USA, The Parthenon Publishing Group, 2004, pp 77–80

    Google Scholar 

  15. Gardulf A, Björvell H, Andersen V, Björkander J, Ericson D, Frøland S, Gustafson R, Hammarström L, Nyström T, Søeberg B, Smith CIE: Lifelong treatment with gammaglobulin to patients with primary antibody deficiencies: The patients' experiences of subcutaneous self-infusions and home therapy. J Adv Nurs 21:917–927, 1995

    Article  PubMed  CAS  Google Scholar 

  16. Gardulf A, Nicolay U, Asensio O, Bernatowska E, Böck A, Costa-Carvalho BT, Granert C, Haag S, Hernández D, Kiessling P, Kus J, Matamoros N, Niehues T, Schmidt S, Schulze I, Borte M: Children and adults with primary antibody deficiencies gain quality of life by subcutaneous IgG self-infusions at home. J Allergy Clin Immunol 114:936–941, 2004

    Article  PubMed  CAS  Google Scholar 

  17. Waniewski J, Gardulf A, Hammarström L: Bioavailability of gammaglobulin after subcutaneous infusions in patients with common variable immunodeficiency. J Clin Immunol 14:90–97, 1994

    Article  PubMed  CAS  Google Scholar 

  18. Gustafson R, Hammarström L: Subcutaneous immunoglobulin replacement therapy. Ellipse 18:45–48, 2002

    Google Scholar 

  19. Högy B, Keinecke H-O, Borte M: Pharmacoeconomic evaluation of immunoglobulin treatment in patients with antibody deficiencies from the perspective of the German Statutory Health Insurance. Eur J Health Econom 50:24–29, 2005

    Article  Google Scholar 

  20. Gardulf A: Rapid subcutaneous immunoglobulin replacement therapy in patients with primary antibody deficiency. Aspects of effectiveness, safety, home therapy, quality of life and costs. Stockholm, Sweden, Karolinska Institutet, 1994 (ISBN 91-628-1403-6)

  21. Bristol DR: Clinical equivalence. J Biopharm Stat 9:561, 1999

    Article  Google Scholar 

  22. Yu Z, Lennon VA: Mechanism of intravenous immune globulin therapy in antibody-mediated autoimmune diseases. N Engl J Med 340:227–228, 1999

    Article  PubMed  CAS  Google Scholar 

  23. Wells JV: Metabolism of immunoglobulins. In Basic and Clinical Immunology, 2nd edn. HH Fudenberg, DP Stites, JL Caldwell, JV Wells (eds). Los Altos, CA, USA, Lange Medical Publishing, 1999, pp 237–245

    Google Scholar 

  24. Ochs HD, Pinciaro PJ and the Octagam Study Group: Octagam 5%, an intravenous IgG product, is efficacious and well tolerated in subjects with primary immunodeficiency diseases. J Clin Immunol 24:309–314, 2004

    Article  PubMed  CAS  Google Scholar 

  25. Adams PF, Hendershot GE, Marano MA: Current estimations from the National Health Interview Study, 1996. National Center for Health Statistics. Vital Health Stat 10(200): 1999

  26. Borte M, Oertelt C, Högy B: Behandlung von patienten mit primären antikörpermangelsyndromen in Deutschland. (Treatment of patients with primary antibody deficiencies in Germany). Klein Pädiatr 217:276–280, 2005 (Abstract in English)

    Article  CAS  Google Scholar 

  27. Gardulf A, Björvell H, Gustafson R, Hammarström L, Smith CIE: Safety of rapid subcutaneous gammaglobulin infusions in patients with primary antibody deficiency. Immunodeficiency 4:81–84, 1993

    PubMed  CAS  Google Scholar 

  28. Björkander J, Wadsworth C, Hansson L-Å: 1040 prophylactic infusions with an unmodified intravenous immunoglobulin product causing few side-effects in patients with antibody deficiency syndromes. Infection 13:102–110, 1985

    Article  PubMed  Google Scholar 

  29. Thampakkul S, Ballow M: Replacement intravenous immune serum globulin therapy in patients with antibody deficiency. Immunol Allergy Clin North Am 21:165–184, 2001

    Article  Google Scholar 

  30. Hansen S, Gustafson R, Smith CIE, Gardulf A: Subcutaneous IgG infusions in patients with primary antibody deficiencies: Decreased time of delivery with maintained safety. Clin Immunol 104:237–241, 2002

    Article  PubMed  CAS  Google Scholar 

  31. Note for guidance on the clinical investigation of human normal immunoglobulin for intravenous administration (IVIg) (CPMP/BPWG/388/95 rev. 1): The European Agency for the Evaluation of Medical Products; Human Medicines Evaluation Unit. Committee for Proprietary Medicinal Products, 1999

  32. Note for guidance on the clinical investigation of human normal immunoglobulin for subcutaneous and intramuscular use (CPMP/BPWG/283/00): The European Agency for the Evaluation of Medical Products; Human Medicines Evaluation Unit. Committee for Proprietary Medicinal Products, 2002 (operation date 2003)

Download references

ACKNOWLEDGMENTS

We are grateful to all the nurses at the local study centers who helped with the study by training and supervising the patients and collecting blood samples and questionnaires. We sincerely thank Cordula Massion at Accovion GmbH, Marburg, Germany for the statistical support. We are also grateful to Hilary Hocking, Östersund, Sweden, for her help with the language revision. This study was supported by ZLB Behring, Marburg, Germany.

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine, Section of Clinical Immunology, The Swedish Centre for Immunodeficiencies, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden

    Ann Gardulf

  2. Department of Laboratory Medicine, Section of Clinical Immunology, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden

    Uwe Nicolay

  3. Servicio de Immunologicia Clinica, Consorcio Hospitalari del Parc Tauli, Sabadell, Spain

    Oscar Asensio

  4. Department of Immunology, Children Memorial Health Institute, Warsaw, Poland

    Ewa Bernatowska

  5. Universitätsklinik für Kinder- und Jugendheilkunde, Vienna, Austria

    Andreas Böck

  6. Department of PediatricsDivision of Allergy, Clinical Immunology and Rheumatology, Federal University of São Paolo, São Paolo, Brazil

    Beatriz Costa Carvalho

  7. Immunodeficiency Unit, Section of Clinical Immunology, Karolinska University Hospital Huddinge, Stockholm, Sweden

    Carl Granert

  8. ZLB Behring GmbH, Marburg, Germany

    Stefan Haag & Peter Kiessling

  9. Department of Allergy, Hospital Universitario La Fe, Valencia, Spain

    Dolores Hernández

  10. National Research Institute of Tuberculosis and Lung Diseases, Warsaw, Poland

    Jan Kus

  11. Servicio de Immunologia, Hospital Universitario Son Dureta, Palma de Mallorca, Spain

    Jaune Pons

  12. Universitätsklinikum Düsseldorf, Heinrich-Heine-Universität, Klinik für Kinder-Onkologie, -Hämatologie und -Immunologie, Düsseldorf, Germany

    Tim Niehues

  13. Medizinische Universitätsklinik, Abteilung Rheumatologie und Klinische Immunologie, Freiburg, Germany

    Sigune Schmidt

  14. Charité Berlin, Humboldt-Universität, Klinik für Pädiatrie mit Schwerpunkt Pneumologie/Immunologie, Berlin, Germany

    Ilka Schulze

  15. Klinik für Kinder- und Jugendmedizin am Städtischen Klinikum, “St. Georg” Leipzig, Akademisches Lehrkrankenhaus der Universität Leipzig, Leipzig, Germany

    Michael Borte

  16. Karolinska University Hospital Huddinge, M 96, SE-141 86, Stockholm, Sweden

    Ann Gardulf

Authors
  1. Ann Gardulf
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Uwe Nicolay
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Oscar Asensio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ewa Bernatowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andreas Böck
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Beatriz Costa Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Carl Granert
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Stefan Haag
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dolores Hernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Peter Kiessling
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jan Kus
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jaune Pons
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Tim Niehues
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Sigune Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Ilka Schulze
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Michael Borte
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ann Gardulf.

Additional information

The first two authors have contributed equally to the manuscript

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gardulf, A., Nicolay, U., Asensio, O. 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 26, 177–185 (2006). https://doi.org/10.1007/s10875-006-9002-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10875-006-9002-x

KEY WORDS:

Search

Navigation