Pınar GÜR ÇETİNKAYA, Deniz Nazire ÇAĞDAŞ AYVAZ, Ayça Burcu ÖKSÜZ, Ayşe ERTOY, Umut HAYRAN, Feride ÖZKAN, Meliha EROL, İlhan TEZCAN

Advantage of the subcutaneous immunoglobulin replacement therapy in primary immunodeficient patients with or without secondary protein loss

In recent years subcutaneous immunoglobulin is widely used for primaryimmunodeficient patients. Subcutaneous administration provides a morestable and higher serum immunoglobulin levels due to continuous andsteady transition from lymphatics to the systemic circulation. We aimed toevaluate the changes in serum immunoglobulin levels under subcutaneousimmunoglobulin therapy in patients with primary immunodeficiency with orwithout secondary protein loss. Nine patients with primary immunodeficiencywho switched to subcutaneous immunoglobulin were enrolled. Age, gender,diagnosis, reasons of transition to subcutaneous route, reasons of secondaryprotein loss were recorded. A questionnaire consisting of frequencies andtypes of infections, side effects observed with intravenous and subcutaneousroutes; date and reason of transition to subcutaneous route were asked toall participants. Serum immunoglobulin levels at the 3rd and the 6th monthsbefore and after subcutaneous route were recorded. Of the 9 patients (M/F=4/5) the median age was 12 years (6.1-28.7) and 5 of them had proteinloss. In total, 444 injections were applied, and all patients experienced localreactions. Infections were more frequent under intravenous than subcutaneousroute (p=0.004). We observed an increase in immunoglobulin levels undersubcutaneous route (p=0.069 at 3rd; p=0.13 at 6th month). This increasewas evident at the 3rd month of transition to subcutaneous route in patientswith protein loss (p=0.080). There was an increase in serum immunoglobulinlevels under subcutaneous route. However, increase was not statisticallysignificant since the study group was small. This increment was prominentin patients with protein loss. Subcutaneous administration may be a goodalternative for primary immunodeficient patients with protein loss whohave persistent low serum immunoglobulin levels despite increments in theintravenous immunoglobulin doses.

PDF

___

1. Bruton OC. Agammaglobulinemia. Pediatrics 1952; 9: 722-728.

2. Berger M, Cupps TR, Fauci AS. Immunoglobulin replacement therapy by slow subcutaneous infusion. Ann Intern Med 1980; 93: 55-56.

3. Roord JJ, van der Meer JW, Kuis M, et al. Home treatment in patients with antibody deficiency by slow subcutaneous infusion of gammaglobulin. Lancet 1982; 1: 689-690.

4. Cunningham-Rundles C, Siegal FP, Smithwick EM, et al. Efficacy of intravenous immunoglobulin in primary humoral immunodeficiency disease. Ann Intern Med 1984; 101: 435-439.

5. Skoda-Smith S, Torgerson TR, Ochs HD. Subcutaneous immunoglobulin replacement therapy in the treatment of patients with primary immunodeficiency disease. Ther Clin Risk Manag 2010; 6: 1-10.

6. Gardulf A, Hammarström L, Smith CI. Home treatment of hypogammaglobulinaemia with subcutaneous gammaglobulin by rapid infusion. Lancet 1991; 338: 162-166.

7. Thomas MJ, Brennan VM, Chapel HH. Rapid subcutaneous immunoglobulin infusions in children. Lancet 1993; 342: 1432-1433.

8. 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 2006; 26: 177-185.

9. Berger M. Principles of and advances in immunoglobulin replacement therapy for primary immunodeficiency. Immunol Allergy Clin North Am 2008; 28: 413-437.

10. 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: 133-141.

11. Nimmerjahn F, Ravetch JV. Anti-inflammatory actions of intravenous immunoglobulin. Annu Rev Immunol 2008; 26: 513-533.

12. Orange JS, Hossny EM, Weiler CR, et al. Use of intravenous immunoglobulin in human disease: a review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol 2006; 117: 525-553.

13. Eijkhout HW, van der Meer JW, Kallenberg CG et al. 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: 165-174.

14. L u c a s M , H u g h - J o n e s K , We l b y A , e t a l . Imunomodulatory therapy to achieve maximum efficacy: doses, monitoring, compliance, and self-infusion at home. J Clin Immunol 2010; 30: 84-89.

15. Fadey M. Calculating the Dose of Subcutaneous Immunoglobulin for Primary Immunodeficiency Disease in Patients Switched from Intravenous to Subcutaneous Immunoglobulin Without the Use of a Dose-Adjustment Coefficient. P T 2013; 768-770.

16. Berger M. Subcutaneous immunoglobulin replacement in primary immunodeficiencies. Clin Immunol 2004; 112: 1-7.

17. Garcia-Lloret M, McGhee S, Chatila T. Immunoglobulin Replacement Therapy in Children. Immunol Allergy Clin North Am 2008; 28: 833-849.

18. Gardulf A, Andersen V, Björkander J, et al. Subcutaneous immunoglobulin replacement in patients with primary antibody deficiencies: safety and costs. Lancet 1995; 345: 365-369.

19. Quinti I, Soresina A, Agostini C, et al. Prospective study on CVID patients with adverse reactions to intravenous or subcutaneous IgG administration. J Clin Immunol 2008; 28: 263-267.

20. Bonagura VR. Dose and outcomes in primary immunodeficiency disorders. Clin Exp Immunol 2014; 178: 7-9.

21. Ochs HD, Gupta S, Kiessling P, et al. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases. J Clin Immunol 2006; 26: 265-273.

22. Jolles S, Stein MR, Longhurst HJ, et al. New Frontiers in Subcutaneous Immunoglobulin. Biol Ther 2011; 1: 1-15.

23. Schiff RI, Rudd C. Alterations in the half-life and clearance of IgG during therapy with intravenous gamma-globulin in 16 patients with severe primary humoral immunodeficiency. J Clin Immunol 1986; 6: 256-264.

24. Cottler-Fox M, Lynch M, Pickle LW, et al. Some but not all benefits of intravenous immunoglobulin therapy after marrow transplantation appear to correlate with IgG trough levels. Bone Marrow Transplant 1991; 8: 27-33.

25. Shah SN, Todoric K, Tarrant TK. Improved outcomes on subcutaneous IgG in patients with humoral immunodeficiency and co-morbid bowel disease. Clin Case Rep Rev 2015; 1: 151-152.

26. Vultaggio A, Azzari C, Milito C, et al. Subcutaneous Immunoglobulin Replacement Therapy in Patients with Primary Immunodeficiency in Routine Clinical Practice: The VISPO Prospective Multicenter Study. Clin Drug Investig 2015; 35: 179-185.

27. Haddad É, Barnes D, Kafal A. Home therapy with subcutaneous immunoglobulins for patients with primary immunodeficiency diseases. Transfus Apher Sci 2012; 46: 315-321.

28. Mankarious S, Lee M, Fischer S, et al. The half-lives of IgG subclasses and specific antibodies in patients with primary immunodeficiency who are receiving intravenously administered immunoglobulin. J Lab Clin Med 1988; 112: 634-640.

29. Steihm R. Rare hypogammaglobulinemic disorders due to immunoglobulin loss. IG Living! 2014; 26-28. (www.IGLiving.com).

30. Blaese RM, Strober W, Levy AL, Waldmann TA. Hypercatabolism of IgG, IgA, IgM, and albumin in the Wiskott-Aldrich syndrome. A unique disorder of serum protein metabolism. J Clin Invest 1971; 50: 2331-2338.