How much gammaglobulin ? INGID VII th Meeting Budapest, October 7, 2006 Rolf Gustafson.

How much gammaglobulin ?

INGID VIIth Meeting

Budapest, October 7, 2006

Rolf Gustafson

Ökad infektionsbenägenhet

1880s Immunotherapy von Behring, Kitasato

1950s Substitution therapyBruton

1980s Immunomodulation Imbach, Barandun

Immunotherapy - a short history


Serum from immunized animals (mainly horses)

1895 Diphtheria antiserum

1908 Meningococcal antiserum

1925 Streptococcal antitoxin

Immunotherapy


1933 Placental extracts Diphteria

Scarlet fever

Polio

Measles

1935 Convalescent human serum Rheumatic fever

Impetigo

Measles

Chicken pox

Scarlet fever

Immunotherapy


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


By help of manipulating the:

ethanol concentration

temperature

pH

Separation of plasma proteins

Rolf Gustafson/Baxter Medical


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

IgG Trace amounts of IgM & IgA

Soluble CD4 & CD8

Soluble HLA

What is gammaglobulin ?


Half - life of IgG

0

10

20

30

40

50

60

70

80

90

100

0 3 6 9 12 15 18 21

IgG

%

Weeks


Gammaglobulin became available in the mid

– 1940s and was used for preventing viral

diseases like:

Measles

Hepatitis A

Gammaglobulin

Bruton´s boy


…………. started as subcutaneous

injections at monthly intervals



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



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



2006

Approved and recommended dose:

400 - 800 mg / kg / month



Evaluation

Clinical outcome

Increasing IgG level



Intravenous infusions



IVIG - IgG levels

0

2

4

6

8

10

12

14

16

18

20

1 2 3 4 5 6 7 8 9 10 11 12 13 14

IgG

g/L

Day


Subcutaneous infusions



SCIG - IgG levels

0

2

4

6

8

10

1 2 3 4 5 6 7 8 9 10 11 12 13 14

IgG

g/L

Days


Indications

X-linked agammaglobulinemia (XLA)

Common variable immunodeficiency (CVID)

Severe combined immunodeficiency (SCID)

Wiskott Aldrich syndrome (WAS)


What about IgG subclass deficiences ?

In selected patients with:

IgG1 deficiency

IgG2 deficiency

IgG3 deficiency



Half - life of IgG3

0

10

20

30

40

50

60

70

80

90

100

0 7 14 21 28 35 42 49

IgG3

%

Days


What about selective IgA deficiency ?

In selected adult patients with:

at least 4 treatments with antibiotics / year


Gammaglobulinbehandling

Gustafson R, Gardulf A, Granert C, Hansen S, Hammarström L

Prophylactic therapy for selective IgA deficiency. Lancet 1997;350:865

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


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

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

How much gammaglobulin ? INGID VII th Meeting Budapest, October 7, 2006 Rolf Gustafson.

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