Evaluation of correlation between dose and clinical outcomes in subcutaneous immunoglobulin replacement therapy

Clinical and Experimental Immunology

Volumn 169, Issue 2, 2012, Pages 172-181

  Orange, J S ^a   Belohradsky, B H ^e   Berger, M ^b   Borte, M ^f   Hagan, J ^c   Jolles, S ^h   Wasserman, R L ^d   Baggish, J S ^b   Saunders, R ⁱ   Grimbacher, B ^g  

^a CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^b CSL Behring LLC   (United States)

^c MAYO CLINIC   (United States)

^d DallasAllergy Immunology and Medical City Children's Hospital   (United States)

^e LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^f UNIVERSITY OF LEIPZIG   (Germany)

^g UNIVERSITY OF FREIBURG   (Germany)

^h UNIVERSITY HOSPITAL OF WALES   (United Kingdom)

ⁱ PHOCUS Services LTD part of the Fishawack Group of Companies   (Switzerland)

Author keywords

Dose; IgG replacement therapy; Immunoglobulin; Primary immunodeficiency; Subcutaneous

Indexed keywords

GAMMAGLOBULIN KABI; GAMMANORM; HUMAN IMMUNOGLOBULIN; IMMUNOGLOBULIN; IMMUNOGLOBULIN G; UNCLASSIFIED DRUG;

AREA UNDER THE CURVE; ARTICLE; BACTERIAL INFECTION; CLINICAL TRIAL (TOPIC); COMPARATIVE STUDY; CORRELATION ANALYSIS; DOSE RESPONSE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; EVALUATION; HUMAN; IMMUNE DEFICIENCY; PHASE 3 CLINICAL TRIAL (TOPIC); POST HOC ANALYSIS; PRIORITY JOURNAL; QUALITY OF LIFE; TREATMENT OUTCOME; UNSPECIFIED SIDE EFFECT;

BACTERIAL INFECTIONS; HUMANS; IMMUNIZATION, PASSIVE; IMMUNOGLOBULIN G; IMMUNOLOGIC DEFICIENCY SYNDROMES; INFUSIONS, SUBCUTANEOUS; TREATMENT OUTCOME;

EID: 84863599753     PISSN: 00099104     EISSN: 13652249     Source Type: Journal    
DOI: 10.1111/j.1365-2249.2012.04594.x     Document Type: Article

References (34)

1. Wasserman RL, Irani AM, Tracy J etal. 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.
2. Eijkhout HW, van der Meer JW, Kallenberg CG etal. The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia. A randomized, double-blind, multicenter crossover trial. Ann Intern Med 2001; 135:165-74.
3. Bonilla FA. Intravenous immunoglobulin: adverse reactions and management. J Allergy Clin Immunol 2008; 122:1238-9.
4. Lucas M, Lee M, Lortan J, Lopez-Granados E, Misbah S, Chapel H. Infection outcomes in patients with common variable immunodeficiency disorders: relationship to immunoglobulin therapy over 22 years. J Allergy Clin Immunol 2010; 125:1354-60.
5. Orange JS, Grossman WJ, Navickis RJ, Wilkes MM. Impact of trough IgG on pneumonia incidence in primary immunodeficiency: a meta-analysis of clinical studies. Clin Immunol 2010; 137:21-30.
6. Quinti I, Soresina A, Guerra A etal. 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; 31:315-22.
7. 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.
8. Quinti I, Pierdominici M, Marziali M etal. European surveillance of immunoglobulin safety results of initial survey of 1243 patients with primary immunodeficiencies in 16 countries. Clin Immunol 2002; 104:231-6.
9. Ochs HD, Fischer SH, Wedgwood RJ etal. Comparison of high-dose and low-dose intravenous immunoglobulin therapy in patients with primary immunodeficiency diseases. Am J Med 1984; 76:78-82.
10. Roifman CM, Levison H, Gelfand EW. High-dose versus low-dose intravenous immunoglobulin in hypogammaglobulinaemia and chronic lung disease. Lancet 1987; 1:1075-7.
11. 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.
12. Moore ML, Quinn JM. Subcutaneous immunoglobulin therapy in pediatric primary antibody deficiency. Pediatr Health 2009; 3:231-40.
13. 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.
14. Gardulf A, Hammarstrom L, Smith CI. Home treatment of hypogammaglobulinaemia with subcutaneous gammaglobulin by rapid infusion. Lancet 1991; 338:162-6.
15. Borte M, Bernatowska E, Ochs HD, Roifman CM. Efficacy and safety of home-based subcutaneous immunoglobulin replacement therapy in paediatric patients with primary immunodeficiencies. Clin Exp Immunol 2011; 164:357-64.
16. 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.
17. Gardulf A, Nicolay U, Asensio O etal. 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.
18. Berger M. Incidence of infection is inversely related to steady-state (trough) serum IgG level in studies of subcutaneous IgG in PIDD. J Clin Immunol 2011; 31:924-6.
19. Hagan JB, Fasano MB, Spector S etal. Efficacy and safety of a new 20% immunoglobulin preparation for subcutaneous administration, IgPro20, in patients with primary immunodeficiency. J Clin Immunol 2010; 30:734-45.
20. Maroto HM, Soler PP, Martin NN, Oliveras AM, Espanol BT, Figueras NC. Subcutaneous gammaglobulin in common variable immunodeficiency. First experience in Spain. An Pediatr (Barc) 2009; 70:111-9.
21. US Food and Drug Administration (FDA). FDA Guidance for industry: safety, efficacy, and pharmacokinetic studies to support marketing of immune globulin intravenous (human) as replacement therapy for primary humoral immunodeficiency. 2008. Available at: (accessed 12 December 2011).
22. 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.
23. Wasserman RL, Melamed I, Kobrynski L etal. 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.
24. Fasth A, Nystrom J. Safety and efficacy of subcutaneous human immunoglobulin in children with primary immunodeficiency. Acta Paediatr 2007; 96:1474-8.
25. Jolles S, Bernatowska E, de Gracia J etal. Efficacy and safety of Hizentra® in patients with primary immunodeficiency after a dose-equivalent switch from intravenous or subcutaneous replacement therapy. Clin Immunol 2011; 141:90-102.
26. R Development Core Team. r: a language and environment for statistical computing. R Foundation for Statistical Computing. 2011. Available at: (accessed 7 December 2011).
27. Chambers JM. Linear models. In: Chambers J, Hastie TJ, eds. Statistical models. Pacific Grove, CA: Wadsworth & Brooks/Cole, 1992:95-145.
28. Yong PFK, Thaventhiran JED, Grimbacher B. 'A rose is a rose is a rose, ' but CVID is not CVID: common variable immune deficiency (CVID), what do we know in 2011? Adv Immunol 2011; 111:47-107.
29. Haddad E, Berger M, Wang EC, Jones CA, Bexon M, Baggish JS. Higher doses of subcutaneous IgG reduce resource utilization in patients with primary immunodeficiency. J Clin Immunol 2012; 32:281-9.
30. Thepot S, Malphettes M, Gardeur A etal. 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.
31. 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.
32. Roifman CM, Schroeder H, Berger M etal. 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; 3:1325-33.
33. Misbah S, Sturzenegger MH, Borte M etal. Subcutaneous immunoglobulin: opportunities and outlook. Clin Exp Immunol 2009; 158 (Suppl. 1):51-9.
34. 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.