Home-Based Subcutaneous Immunoglobulin Versus Hospital-Based Intravenous Immunoglobulin in Treatment of Primary Antibody Deficiencies: Systematic Review and Meta Analysis
First Online: 23 June 2012 Received: 25 January 2012 Accepted: 04 June 2012 DOI:
Cite this article as: Abolhassani, H., Sadaghiani, M.S., Aghamohammadi, A. et al. J Clin Immunol (2012) 32: 1180. doi:10.1007/s10875-012-9720-1 Abstract
Immunoglobulin replacement by the subcutaneous route (SCIg) for the prophylactic treatment of primary or secondary antibody deficient patients has been introduced as an alternative to conventional intravenous administration (IVIg). This is a systematic review of all eligible studies comparing efficacy and safety of IVIg and SCIg. Retrospective and prospective cohort studies and randomized, controlled trials comparing SCIg to IVIg were identified from MEDLINE, EMBASE, CINAHL, AMED, CSR, ISI and Cochrane Database without restriction on publication date and language. If possible, meta-analysis was performed by using the Review Manager software. A total of 47 articles with 1,484 compared cases were reviewed. Subcutaneous immunoglobulin replacement achieved acceptable IgG trough level, low incidence of side effects, efficacy similar to IVIg infusions, better health related quality of life and treatment satisfaction, and faster functional recovery with less time off work. Because of the heterogeneity of the reports, meta-analysis had to be performed by random effect method for IgG trough levels [OR (odds ratio) = 1.00, range = 0.84–1.15;
p < 0.01], infection rates (OR = 0.59, range = 0.36–0.97; p = 0.04), and adverse events (OR = 0.09, range = 0.07–0.11; p < 0.001), which showed significant preference of SCIg over IVIg. Based on the analysis of published reports, changing immunoglobulin replacement therapy from IVIg to SCIg may be of benefit to qualified patients with primary immunodeficiency. These advantages, having been demonstrated in numerous studies,make medical, practical and economic sense to consider switching patients with antibody deficiency from IVIg to SCIg. Keywords Immunoglobulin replacement therapy intravenous subcutaneous efficacy Abbreviations SCIg
Primary antibody deficiency
Radosevich M, Burnouf T. Intravenous immunoglobulin G: trends in production methods, quality control and quality assurance. Vox Sang. 2010;98:12–28.
Rezaei N, Abolhassani H, Aghamohammadi A, Ochs HD. Indications and safety of intravenous and subcutaneous immunoglobulin therapy. Expert Rev Clin Immunol. 2011;7:301–16.
Berger M, Cupps TR, Fauci AS. Immunoglobulin replacement therapy by slow subcutaneous infusion. Ann Intern Med. 1980;93:55–6.
Cunningham-Rundles C, Siegal FP, Smithwick EM, Lion-Boule A, Cunningham-Rundles S, O'Malley J, et al. Efficacy of intravenous immunoglobulin in primary humoral immunodeficiency disease. Ann Intern Med. 1984;101:435–9.
Quartier P, Debre 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;134:589–96.
Webb DB, Kendra JR, Gross E, Stamatakis JD. Infusion of intravenous immunoglobulin via implantable subcutaneous catheter. Lancet. 1991;337:1617–8.
Gaspar J, Gerritsen B, Jones A. Immunoglobulin replacement treatment by rapid subcutaneous infusion. Arch Dis Child. 1998;79:48–51.
Arora R, Newton TC, Nelson MR. Subcutaneous immunoglobulin therapy in an 11-year-old patient with common variable immunodeficiency and von Willebrand disease. Ann Allergy Asthma Immunol. 2007;99:367–70.
Gardulf A, Hammarstrom L, Smith CI. Home treatment of hypogammaglobulinaemia with subcutaneous gammaglobulin by rapid infusion. Lancet. 1991;338:162–6.
Chapel HM, Spickett GP, Ericson D, Engl W, Eibl MM, Bjorkander J. The comparison of the efficacy and safety of intravenous versus subcutaneous immunoglobulin replacement therapy. J Clin Immunol. 2000;20:94–100.
Thomas MJ, Brennan VM, Chapel HH. Rapid subcutaneous immunoglobulin infusions in children. Lancet. 1993;342:1432–3.
Abrahamsen TG, Sandersen H, Bustnes A. Home therapy with subcutaneous immunoglobulin infusions in children with congenital immunodeficiencies. Pediatrics. 1996;98:1127–31.
Nicolay U, Kiessling P, Berger M, Gupta S, Yel L, Roifman CM, et al. Health-related quality of life and treatment satisfaction in North American patients with primary immunedeficiency diseases receiving subcutaneous IgG self-infusions at home. J Clin Immunol. 2006;26:65–72.
Ochs HD, Gupta S, Kiessling P, Nicolay U, Berger M. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases. J Clin Immunol. 2006;26:265–73.
Eibl MM. History of immunoglobulin replacement. Immunol Allergy Clin North Am. 2008;28:737–64.
Gardulf A, Nicolay U. Replacement IgG therapy and self-therapy at home improve the health-related quality of life in patients with primary antibody deficiencies. Curr Opin Allergy Clin Immunol. 2006;6:434–42.
Jolles S, Sleasman JW. Subcutaneous immunoglobulin replacement therapy with Hizentra, the first 20 % SCIG preparation: a practical approach. Adv Ther. 2011;28:521–33.
Liu Z, Albon E, Hyde C. The effectiveness and cost effectiveness of immunoglobulin replacement therapy for primary immunodeficiency and chronic lymphocytic leukaemia: a systematic review and economic evaluation. West Midlands Health Technology Assessment Collaboration. 2005;54:1–154.
Ho C, Membe SK, Cimon K. An overview of subcutaneous vs. intravenous immunoglobulin for primary immunodeficiencies: systematic review and economic analysis. Canadian Agency for Drugs and Technologies in Health HTA. 2008;36:1–8.
Berger M. Subcutaneous administration of IgG. Immunol Allergy Clin North Am. 2008;28:779–802.
Moore ML, Quinn JM. Subcutaneous immunoglobulin replacement therapy for primary antibody deficiency: advancements into the 21st century. Ann Allergy Asthma Immunol. 2008;101:114–21.
Kittner JM, Grimbacher B, Wulff W, Jager B, Schmidt RE. Patients' attitude to subcutaneous immunoglobulin substitution as home therapy. J Clin Immunol. 2006;26:400–5.
Hoffmann F, Grimbacher B, Thiel J, Peter HH, Belohradsky BH. Home-based subcutaneous immunoglobulin G replacement therapy under real-life conditions in children and adults with antibody deficiency. Eur J Med Res. 2010;15:238–45.
Thepot S, Malphettes M, Gardeur A, Galicier L, Asli B, Karlin L, et al. Immunoglobulin dosage and switch from intravenous to subcutaneous immunoglobulin replacement therapy in patients with primary hypogammaglobulinemia: decreasing dosage does not alter serum IgG levels. J Clin Immunol. 2010;30:602–6.
Jolles S, Bernatowska E, de Gracia J, Borte M, Cristea V, Peter HH, et al. Efficacy and safety of Hizentra((R)) in patients with primary immunodeficiency after a dose-equivalent switch from intravenous or subcutaneous replacement therapy. Clin Immunol. 2011;141:90–102.
Fasth A, Nystrom J. Quality of life and health-care resource utilization among children with primary immunodeficiency receiving home treatment with subcutaneous human immunoglobulin. J Clin Immunol. 2008;28:370–8.
Gardulf A, Andersen V, Bjorkander J, Ericson D, Froland SS, Gustafson R, et al. Subcutaneous immunoglobulin replacement in patients with primary antibody deficiencies: safety and costs. Lancet. 1995;345:365–9.
Fasth A, Nystrom J. Safety and efficacy of subcutaneous human immunoglobulin in children with primary immunodeficiency. Acta Paediatr. 2007;96:1474–8.
Berger M, Murphy E, Riley P, Bergman GE. Improved quality of life, immunoglobulin G levels, and infection rates in patients with primary immunodeficiency diseases during self-treatment with subcutaneous immunoglobulin G. South Med J. 2010;103:856–63.
Melamed I, McDonald A, Neff A, Beck A. An analysis of safety and tolerability data on 10%, 16%, and 20% formulations of subcutaneous immunoglobulin (IGSC). J Allergy Clin Immunol. 2011;127:AB16.
Stiehm ER. Human intravenous immunoglobulin in primary and secondary antibody deficiencies. Pediatr Infect Dis J. 1997;16:696–707.
Chouksey A, Duff K, Wasserbauer N, Berger M. Subcutaneous immunoglobulin-g replacement therapy with preparations currently available in the United States for intravenous or intramuscular use: reasons and regimens. Allergy Asthma Clin Immunol. 2005;1:120–30.
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;26:177–85.
Ratko TA, Burnett DA, Foulke GE, Matuszewski KA, Sacher RA. Recommendations for off-label use of intravenously administered immunoglobulin preparations. JAMA. 1995;273:1865–70.
Eijkhout HW, van den Broek PJ, van der Meer JW. Substitution therapy in immunodeficient patients with anti-IgA antibodies or severe adverse reactions to previous immunoglobulin therapy. Neth J Med. 2003;61:213–7.
Sundin U, Nava S, Hammarstrom L. Induction of unresponsiveness against IgA in IgA-deficient patients on subcutaneous immunoglobulin infusion therapy. Clin Exp Immunol. 1998;112:341–6.
Borte M, Oertelt C, Hogy B. Treatment of patients with primary antibody deficiencies in Germany. Klin Padiatr. 2005;217:276–80.
Beauté J, Levy P, Millet V, Debré M, Dudoit Y, Le Mignot L, et al. Economic evaluation of immunoglobulin replacement in patients with primary antibody deficiencies. Clin Exp Immunol. 2010;160:240–5.
Membe SK, Ho C, Cimon K, Morrison A, Kanani A, Roifman CM. Economic assessment of different modalities of immunoglobulin replacement therapy. Immunol Allergy Clin North Am. 2008;28:861–74.
Hogy B, Keinecke H, Borte M. Pharmacoeconomic evaluation of immunoglobulin treatment in patients with antibody deficiencies from the perspective of the German statutory health insurance. Eur J Health Econ. 2005;6:24–9.
Berger M. Subcutaneous immunoglobulin replacement in primary immunodeficiencies. Clin Immunol. 2004;112:1–7.
Ochs H, Fischer S, Lee M, Delson E, Kingdon H, Wedgwood R. Intravenous Ig home treatment for patients with primary immunodeficiency diseases. Lancet. 1986;1:610–1.
Ashida E, Saxon A. Home intravenous Ig therapy by self-administration. J Clin Immunol. 1986;6:306–9.
Gardulf A, Bjorvell H, Gustafson R, Hammarstrom L, Smith CI. Safety of rapid subcutaneous gammaglobulin infusions in patients with primary antibody deficiency. Immunodeficiency. 1993;4:81–4.
Chapel H, Brennan V, Delson E. Immunoglobulin replacement therapy by self-infusion at home. Clin Exp Immunol. 1988;73:160–2.
Quinti I, Pierdominici M, Marziali M, Giovannetti A, Donnanno S, Chapel H, et al. European surveillance of immunoglobulin safety–results of initial survey of 1243 patients with primary immunodeficiencies in 16 countries. Clin Immunol. 2002;104:231–6.
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;139:133–41.
Koleba T, Ensom M. Pharmacokinetics of intravenous immunoglobulin: a systematic review. Pharmacotherapy. 2006;26:813–27.
Gustafson R, Gardulf A, Hansen S, Leibl H, Engl W, Linden M, et al. Rapid subcutaneous immunoglobulin administration every second week results in high and stable serum immunoglobulin G levels in patients with primary antibody deficiencies. Clin Exp Immunol. 2008;152:274–9.
Notarangelo LD, Plebani A, Mazzolari E, Soresina A, Bondioni MP. Genetic causes of bronchiectasis: primary immune deficiencies and the lung. Respiration. 2007;74:264–75.
Dani B, Platz R, Tzannis S. High concentration formulation feasibility of human IgG for subcutaneous administration. J Pharm Sci. 2007;96:1504–17.
Frost G. Recombinant human hyaluronidase (rHUPH20): an enabling platform for subcutaneous drug and fluid administration. Expert Opin Drug Deliv. 2007;4:427–40.
Misbah S, Sturzenegger MH, Borte M, Shapiro RS, Wasserman RL, Berger M, et al. Subcutaneous immunoglobulin: opportunities and outlook. Clin Exp Immunol. 2009;158:51–9.
Hizentra Assessment report,CSL Behring European Medicines Agency. 2011;2127 1-56.
Borte M, Pac M, Serban M, Gonzalez-Quevedo T, Grimbacher B, Jolles S, et al. Efficacy and safety of hizentra(R), a new 20 % immunoglobulin preparation for subcutaneous administration, in pediatric patients with primary immunodeficiency. J Clin Immunol. 2011;31:752–61.
Wasserman RL, Melamed I, Kobrynski L, Strausbaugh SD, Stein MR, Sharkhawy M, et al. Efficacy, safety, and pharmacokinetics of a 10 % liquid immune globulin preparation (GAMMAGARD LIQUID, 10 %) administered subcutaneously in subjects with primary immunodeficiency disease. J Clin Immunol. 2011;31:323–31.
Wasserman RL, Irani AM, Tracy J, Tsoukas C, Stark D, Levy R, et al. Pharmacokinetics and safety of subcutaneous immune globulin (human), 10 % caprylate/chromatography purified in patients with primary immunodeficiency disease. Clin Exp Immunol. 2010;161:518–26.
Shapiro R. Subcutaneous immunoglobulin therapy by rapid push is preferred to infusion by pump: a retrospective analysis. J Clin Immunol. 2010;30:301–7.
Maroto Hernando M, Soler Palacin P, Martin Nalda N, Oliveras Arenas M, Espanol Boren T, Figueras Nadal C. [Subcutaneous gammaglobulin in common variable immunodeficiency. First experience in Spain]. An Pediatr (Barc). 2009;70:111–9.
Desai SH, Chouksey A, Poll J, Berger M. A pilot study of equal doses of 10 % IGIV given intravenously or subcutaneously. J Allergy Clin Immunol. 2009;124:854–6.
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;28:263–7.
Gardulf A, Borte M, Ochs HD, Nicolay U. Prognostic factors for health-related quality of life in adults and children with primary antibody deficiencies receiving SCIG home therapy. Clin Immunol. 2008;126:81–8.
Horn J, Thon V, Bartonkova D, Salzer U, Warnatz K, Schlesier M, et al. Anti-IgA antibodies in common variable immunodeficiency (CVID): diagnostic workup and therapeutic strategy. Clin Immunol. 2007;122:156–62.
Sigstad HM, Stray-Pedersen A, Froland SS. Coping, quality of life, and hope in adults with primary antibody deficiencies. Health and Quality of Life Outcomes. 2005;3:1–31.
Pac M, Bernatowska E. Polish experience with immunoglobulin replace ment treatment by subcutaneous infusion. Centr Eur J Immunol. 2005;30:78–82.
Nicolay U, Haag S, Eichmann F, Herget S, Spruck D, Gardulf A. Measuring treatment satisfaction in patients with primary immunodeficiency diseases receiving lifelong immunoglobulin replacement therapy. Qual Life Res. 2005;14:1683–91.
Kirmse J, Weiler CR. Subcutaneous immunoglobulin (SCIG) therapy: review of 51 patients. J Allergy Clin Immunol. 2005;115:S86.
Johnson N, Dash CH, Gooi HC, Toolan J, Exley A, Henderson K, et al. Patients’ views on subcutaneous IgG (SCIG) Home Therapy: results from The UK Subgam® Study. BPL. 2004;1:1.
Gardulf A, Nicolay U, Math D, Asensio O, Bernatowska E, Bock A, et al. Children and adults with primary antibody deficiencies gain quality of life by subcutaneous IgG self-infusions at home. J Allergy Clin Immunol. 2004;114:936–42.
Radinsky S, Bonagura VR. Subcutaneous immunoglobulin infusion as an alternative to intravenous immunoglobulin. J Allergy Clin Immunol. 2003;112:630–3.
Radinsky S, Bonagura VR. Subcutaneous immunoglobulin infusion as an alternative to intravenous immunoglobulin: a fllow-up of three patients. J Allergy Clin Immunol. 2002;109:S187.
Stiehm ER, Casillas AM, Finkelstein JZ, Gallagher KT, Groncy PM, Kobayashi RH, et al. Slow subcutaneous human intravenous immunoglobulin in the treatment of antibody immunodeficiency: use of an old method with a new product. J Allergy Clin Immunol. 1998;101:848–9.
Gardulf A, Bjorvell H, Andersen V, Bjorkander J, Ericson D, Froland SS, et al. Lifelong treatment with gammaglobulin for primary antibody deficiencies: the patients' experiences of subcutaneous self-infusions and home therapy. J Adv Nurs. 1995;21:917–27.
Waniewski J, Gardulf A, Hammarstrom L. Bioavailability of gamma-globulin after subcutaneous infusions in patients with common variable immunodeficiency. J Clin Immunol. 1994;14:90–7.
Gardulf A, Bjorvell H, Gustafson R, Hammarstrom L, Smith CI. The life situations of patients with primary antibody deficiency untreated or treated with subcutaneous gammaglobulin infusions. Clin Exp Immunol. 1993;92:200–4.
PubMed CrossRef Copyright information
© Springer Science+Business Media, LLC 2012