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

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Serum from immunized animals (mainly horses)

1895 Diphtheria antiserum

1908 Meningococcal antiserum

1925 Streptococcal antitoxin

Immunotherapy

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1933 Placental extracts Diphteria

Scarlet fever

Polio

Measles

1935 Convalescent human serum Rheumatic fever

Impetigo

Measles

Chicken pox

Scarlet fever

Immunotherapy

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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

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By help of manipulating the:

ethanol concentration

temperature

pH

Separation of plasma proteins

Rolf Gustafson/Baxter Medical

Rolf Gustafson/Baxter Medical

Rolf Gustafson/Baxter Medical

Ökad infektionsbenägenhet

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 ?

Rolf Gustafson/Baxter Medical

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

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Gammaglobulin became available in the mid

– 1940s and was used for preventing viral

diseases like:

Measles

Hepatitis A

Gammaglobulin

Bruton´s boy

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…………. started as subcutaneous

injections at monthly intervals

Substitution therapy

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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

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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

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2006

Approved and recommended dose:

400 - 800 mg / kg / month

Substitution therapy

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Evaluation

Clinical outcome

Increasing IgG level

Substitution therapy

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Intravenous infusions

Substitution therapy

Rolf Gustafson/Baxter Medical

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

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Subcutaneous infusions

Substitution therapy

Rolf Gustafson/Baxter Medical

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

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Indications

X-linked agammaglobulinemia (XLA)

Common variable immunodeficiency (CVID)

Severe combined immunodeficiency (SCID)

Wiskott Aldrich syndrome (WAS)

Substitution therapy

What about IgG subclass deficiences ?

In selected patients with:

IgG1 deficiency

IgG2 deficiency

IgG3 deficiency

Substitution therapy

Rolf Gustafson/Baxter Medical

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

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What about selective IgA deficiency ?

In selected adult patients with:

at least 4 treatments with antibiotics / year

Substitution therapy

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

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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