Ann Gardulf, R'N', PhD, Associate Professor

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Home Treatment with Subcutaneous Immunoglobin
Ann Gardulf, R.N., PhD, Associate
Professor Karolinska Institutet and Karolinska
University Hospital Stockholm, Sweden ann.gardulf_at_
ki.se

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Antibody deficiencies

• Lack of - or too low levels of antibodies will
  result in an increased frequency and severity of
  bacterial infections in the respiratory tract and
  gastrointestinal canal
• The missing antibodies need to be replaced
• Replacement therapy or substitution therapy
• Gammaglobulin is a concentrate of IgG and used
  for the replacement therapy

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PID in Europe

• Disease Prevalence
• Diabetes (type 1) 1700
• Multiple sclerosis (MS) 11000
• Rhematoid arthritis (RA) 1125-200
• PID 1250-500
• The current diagnosis of PID classify them as
  rare diseases. However, studies show that with
  improved diagnosis, the prevalence in Europe
  could be as much as 1250-500.

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PID sufferers in Europe

• No. of people with PID
• Sweden (population 9 million) 36 000
• The Netherlands
• (population 16 million) 52 000
• Enlarged European Union 1 940 000
• (population 485 million)

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Antibody deficiencies

• Lack of - or too low levels of antibodies will
  result in an increased frequency of bacterial
  infections in the respiratory tract and
  gastrointestinal canal
• The missing antibodies need to be replaced
• Replacement therapy or substitution therapy
• Gammaglobulin (IgG) is a concentrate of
  antibodies and used for the therapy

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35 mL/hour
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Dosing SCIG per week

• SCIG 100 mg/kg/week (400 mg/kg/month)
• 30 kg 20 mL
• 60 kg 40 mL
• 80 kg 50 mL

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Rapid Subcutaneous IgG Replacement Therapy
Infusion technique
Infusion- Adults volumes The total infusion
volume is divided between 2-4 infusion
sites 10-15 mL/infusion site (max. 20-25
mL) Children Often 1 (-2) infusions
site/-s 5-10 mL/infusion site
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Safety Local tissue reactions
Rapid Subcutaneous IgG Replacement Therapy

• It is normal to expect local tissue reactions in
  the beginning of the therapy (swelling, redness,
  induration)
• The local reactions declined over time!

Gardulf A, Nicolay U, Asencio O et al. J Clin
Immunol 2006
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Rapid Subcutaneous IgG Replacement Therapy
What are the advantages?
Effectiveness Normal/high S-IgG S-IgG subclass
levels Good protection against
infections Stable S-IgG level Safety Low
risk for systemic adverse reactions No
transmission of hepatitis C virus Easy Easy
to learn and to set up for children,
technique adults and elderly No venous access
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Rapid Subcutaneous IgG Replacement Therapy
What are the advantages?
Patient Facilitate self-infusions at home
after Satisfaction patient education Quality of
life Improved self-reported health and
quality of life (QoL)
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Safety Local tissue reactions
Rapid Subcutaneous IgG Replacement Therapy
Gardulf A, Nicolay U, Asencio O et al. J Clin
Immunol 2006
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Nurse-Run Home-Therapy Training Program
Rapid Subcutaneous IgG Replacement Therapy

• Groups of 5 patients
• Education and training once/week, 8 times
• primary antibody deficiencies
• aim and importance of IgG therapy
• infections
• systemic adverse reactions
• self-care and prevention
• behaviour changes
• self-infusion technique
• Follow-up after 2 months

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Patient education
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Preference IgG Administration Route 10 months ()
Rapid Subcutaneous IgG Replacement Therapy
Pre-treatment IVIG
Pre-treatment SCIG
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Preference home- or hospital? 10 months ()
Rapid Subcutaneous IgG Replacement Therapy
Pre-treatment IVIG
Pre-treatment SCIG
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Rapid Subcutaneous IgG Replacement Therapy
What are the advantages?
Patient Facilitate self-infusions at home
after Satisfaction patient education Quality of
life Improved self-reported health and
quality of life (QoL) Costs Lower cost for
the healthcare services Lower cost for the
patients/families
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SCIG therapy and costs
Rapid Subcutaneous IgG Replacement Therapy

• The introduction of SCIG antibody therapy at home
  instead of IVIG at the hospital has been found to
  reduce the annual cost by more than 10,000 US
  (1993 prices) (Gardulf et al., 1995)
• The introduction of antibody therapy at home
  reduced the patient/family out-of-pocket
  expenses by more than 600 and the total
  patient/family-borne cost by 50 year
• (Gardulf, Möller Jonssson, 1995)

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SCIG in Sweden

• 45,000 SCIG infusions per year (to adults)
• The method has been used for
• 20 years ..
• Totally 2,000 litre of gammaglobulin is given
  every year to adults with PID

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Literature

• Gardulf A, Nicolay U. Replacement IgG therapy and
  self-therapy at home improve the health-related
  quality of life in patients with primary antibody
  deficiencies. Current Opinion in Allergy
  Clinical Immunology 20066434-442.
• Gardulf A. Immunoglobulin Treatment for Primary
  Antibody Deficiencies Advantages of the
  Subcutaneous Route. BioDrug 200721105-116.

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Rapid Subcutaneous IgG Replacement Therapy
The importance of a correct infusion technique
100
90
80
70
60
Subjects with injection site reactions ()
50
40
30
20
10
0
0
10
20
30
40
50
60
70
Infusion
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Mean S-IgG trough levels (100 mg/kg/week)Adults
with CVID or XLA
Rapid Subcutaneous IgG Replacement Therapy
Gardulf, Andersen, Björkander et al. Lancet
1995345365-69
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Mean S-IgG Levels (g/L) (n52) (week 16-43)
Rapid Subcutaneous IgG Replacement Therapy
Baseline
Children pre-IVIG 7.8
Teenagers/adults pre-IVIG 8.6
Monthly cumulative SCIG dose equivalent to
previous cumulative IVIG dose
Gardulf A, Nicolay U, Asencio O et al. J Clin
Immunol 2006
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Can the SCIG therapy be used to all patients?
Rapid Subcutaneous IgG Replacement Therapy

• Children, adults and elderly
• During pregnancy
• X-linked agammaglobulinemia (XLA), common
  variable immunodeficiency (CVID), infections
  prone patients with IgG subclass deficiencies,
  infections prone patients with selective IgA
  deficiency
• SCID, Wiskott-Aldrich syndrome
• Carefulness with patients on warfarin treatment
  (but not a contraindication!)
• Patients with severe protein losses (e.g.
  inflammatory bowel diseases) may also need IVIG
  therapy
• Self-infusions at home? Suitable

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Rapid Subcutaneous IgG Replacement Therapy
What are the advantages?
Effectiveness Normal/high S-IgG S-IgG subclass
levels Stable S-IgG level Good protection
against infections No need for
pre-medication Safety Low risk for systemic
adverse reactions No transmission of
hepatitis C virus
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Safety (n60) Systemic adverse reactions
Rapid Subcutaneous IgG Replacement Therapy

• Totally 2,297 infusions
• 28 systemic adverse reactions (28/2,287) 1
• 13 patients (1 teenager)
• 21 mild
• 3 moderate (one teenager with 1 reaction)
• 1 suspected serious reaction (adult)

Gardulf A, Nicolay U, Asencio O et al. J Clin
Immunol 2006
27
Safety Local tissue reactions
Rapid Subcutaneous IgG Replacement Therapy

• Local tissue reactions are normal and expect
• - especially in the beginning of the treatment
• Most common are swelling, soreness and redness
• No persisting tissue changes, no skin infections

Gardulf, Andersen, Björkander et al. Lancet
1995345365-69
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Safety Local tissue reactions
Rapid Subcutaneous IgG Replacement Therapy

• What do the patient experience? (n165)
• (1 not at all troublesome)
• Swelling 19 (median score)
• Soreness 29
• Redness 5
• No more local reactions with increased infusion
  rate (35 mL/h)
• (Express SCIG infusion)

Gardulf, Andersen, Björkander et al. Lancet
1995345365-69
Hansen, Gustafson, Smith,Gardulf Clin Immunol 2002
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Rapid Subcutaneous IgG Replacement Therapy
What are the advantages?
Effectiveness Normal/high S-IgG S-IgG subclass
levels Stable S-IgG level Good protection
against infections No need for
pre-medication Safety Low risk for systemic
adverse reactions No transmission of hepatitis
C virus Easy Easy to learn and to set up for
children, technique adults and elderly No
venous access
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SCIG therapy and costs
Rapid Subcutaneous IgG Replacement Therapy

• The cost of SCIG administration in the USA is 48
  US compared to IVIG at home with nursing care
  164 to 314 US (Radinsky Bonagura, 2003)
• .it may be expected that cost savings of US
  2,000-5,000 per patient per year by SCIG or IVIG
  at home (Berger, 2004)