How much gammaglobulin ?

1. How much gammaglobulin ? INGID VIIth Meeting Budapest, October 7, 2006 Rolf Gustafson

2. 1880s Immunotherapy von Behring, Kitasato 1950s Substitution therapy Bruton 1980s Immunomodulation Imbach, Barandun Immunotherapy - a short history Ökad infektionsbenägenhet

3. Serum from immunized animals (mainly horses) 1895 Diphtheria antiserum 1908 Meningococcal antiserum 1925 Streptococcal antitoxin Immunotherapy Ökad infektionsbenägenhet

4. 1933Placental extracts Diphteria Scarlet fever Polio Measles 1935Convalescent human serum Rheumatic fever Impetigo Measles Chicken pox Scarlet fever Immunotherapy Ökad infektionsbenägenhet

5. 1940 The US National Research Council asked Dr. Edwin Cohn to identify a stable blood derivate or substitute. 1941 The American Red Cross began collecting blood. A grant of 10,000 USD for large scale production of human albumin was given. Substitution therapy Ökad infektionsbenägenhet

6. By help of manipulating the: ethanol concentration temperature pH Separation of plasma proteins Ökad infektionsbenägenhet

7. Rolf Gustafson/Baxter Medical

8. Rolf Gustafson/Baxter Medical

9. Rolf Gustafson/Baxter Medical

10. WHO International Red Cross International Society of Transfusion (ISBT) Council of Europe European Union European Agency for the Evaluation of Medicinal Products (EMEA) FDA Statements, Directives & Resolutions Ökad infektionsbenägenhet

11. IgG Trace amounts of IgM & IgA Soluble CD4 & CD8 Soluble HLA What is gammaglobulin ?

12. Half - lifeof IgG % Weeks Rolf Gustafson/Baxter Medical

13. Gammaglobulin became available in the mid – 1940s and was used for preventing viral diseases like: Measles Hepatitis A Gammaglobulin Ökad infektionsbenägenhet

14. Bruton´s boy

15. …………. started as subcutaneous injections at monthly intervals Substitution therapy Ökad infektionsbenägenhet

16. 1950s - 1960s Medical Research Council in England Data from 176 patients 25 mg / kg / week 50 mg / kg / week fewer deaths less cases of pneumonia IgG 1.2 – 2.6 g/L IgG 2.9 – 3.8 g/L Substitution therapy Ökad infektionsbenägenhet

17. Late 1980s consencus of giving 300 - 400 mg / kg / month IgG 4 – 5 g/L 1987 Roifman et al. reported that 600 mg / kg / month was better than 200 mg / kg / month IgG > 5 g / L Substitution therapy Ökad infektionsbenägenhet

18. 2006 Approved and recommended dose: 400 - 800 mg / kg / month Substitution therapy Ökad infektionsbenägenhet

19. Evaluation Clinical outcome Increasing IgG level Substitution therapy Ökad infektionsbenägenhet

20. Intravenous infusions Substitution therapy Ökad infektionsbenägenhet

21. IVIG - IgG levels g/L Day Rolf Gustafson/Baxter Medical

22. Subcutaneous infusions Substitution therapy Ökad infektionsbenägenhet

23. SCIG - IgG levels g/L Days Rolf Gustafson/Baxter Medical

24. Indications X-linked agammaglobulinemia (XLA) Common variable immunodeficiency (CVID) Severe combined immunodeficiency (SCID) Wiskott Aldrich syndrome (WAS) Substitution therapy Ökad infektionsbenägenhet

25. What about IgG subclass deficiences ? In selected patients with: IgG1 deficiency IgG2 deficiency IgG3 deficiency Substitution therapy

26. Half - lifeof IgG3 % Days Rolf Gustafson/Baxter Medical

27. What about selective IgA deficiency ? In selected adult patients with: at least 4 treatments with antibiotics / year Substitution therapy Ökad infektionsbenägenhet

28. Gustafson R, Gardulf A, Granert C, Hansen S, Hammarström L Prophylactic therapy for selective IgA deficiency. Lancet 1997;350:865 Gammaglobulinbehandling SCIG therapy in IgA deficiency IgG therapy: 100 mg/kg/week Infections per year Before IgG therapy During IgG therapy 0 – 1 0 5 2 – 3 0 5 ≥ 4 10 0

29. What is the goal with patient education ? The goal is … that the patient becomes an active and encouraged part in the decision-making process and have the knowledge about self-care activities and behaviors that foster health and health-related quality of life instead of being a passive receiver of information. A. Gardulf, 2002 Patient training & education Ökad infektionsbenägenhet

30. Training & education should include knowledge & understanding of: primary antibody deficiencies aim and importance of IgG therapy infections & antibiotic treament systemic adverse reactions self-care and prevention behaviour changes self-infusion technique Home-therapy training program – the key to success