PRIMARY & SECONDARY
ANTIBODY DEFICIENCY
ANTIBODIES
&
IMMUNOGLOBULINS
PRIMARY ANTIBODY
DEFICIENCY
The European internet-based patient and research database for primary immunodeficiencies: results 2006-2008.
Gathman et al., Clin Exp Immunol (2009); 157 Suppl 1: 3-11.
Brit Med J (1989); 298: 516-7
THERAPEUTIC
IMMUNOGLOBULIN
• 1970s
- IMIg
• 1980s
- IVIg
• 1990s
- IVIg, SCIg
• 2000s
- product safety
- infusion rates / concentration
- immunoglobulin retrieval
REPLACEMENT THERAPY
TREATMENT OUTCOMES
Wood et al. Clin Exp Immunol (2007); 149: 410-423
EFFICACY & ADVERSITY
•
•
•
•
Immunoglobulin
Excipients
Soluble CD4/ CD8/ HLA
Cytokines
Clin Exp Immunol (2004); 136: 111-3
IVIg & SCIg
ESID Register 2009
HOME THERAPY
2008 and 2011
SAME OLD SAME OLD
•
•
•
•
Core of PID management
No alternatives
Lifelong requirement (usually)
Effective
(bacterial infection, antibiotic usage, QoL, hospitalisation, life expectancy)
• Dose requirement  in:
- frequent breakthrough infections
- chronic inflammation / tissue damage
- poor prognosis disease variants
WHAT’S NEW?
The three Rs:
• Reorganisation
• Reclassification
• Aarrrgh
- ongoing uncertainties over dosing / target levels
DOSE?
Impact of trough IgG on pneumonia incidence in primary immunodeficiency: A meta-analysis of clinical studies.
Orange JS et al. Clinical Immunology (2010); 137: 21-30
DOSE: INDIVIDUALISATION
‘The goal of replacement therapy should be to improve clinical
outcome and not to reach a particular IgG trough level.’
J Allergy Clin Immunol (2010);125:1354-60
DOSE: INDIVIDUALISATION
‘….individualizing the dosage….is preferable to using mean pharmacokinetic
parameters.’
Clin Immunol (2011);139:133-41
RECLASSIFICATION
• Specific Antibody Deficiency

• Kawasaki Disease
 ‘Other’ Section
REORGANISATION
PRIMARY ANTIBODY
DEFICIENCY DISORDERS
SPECIFIC DISORDERS
Thymoma with immunodeficiency
(Good’s Syndrome)
Combined immunodeficiencies requiring
haemopoietic stem cell transplantation
(HSCT)
Specific antibody deficiency
(SAD)
Transient hypogammaglobulinaemia of infancy
(THI)
SPECIFIC DISORDERS
DISORDER
GOOD’S
RECOMMENDATION / REQUIREMENT
Profound B cell depletion / significant antibody deficiency
HSCT
Duration based on B cell reconstitution post-transplantation
SAD
Robust application of selection criteria
THI
Define planned duration of therapy prior to initiation
(GRADE C, LEVEL III)
SUMMARY: PID
SECONDARY ANTIBODY
DEFICIENCY
ANTIBODY
DEFICIENCY
PRIMARY
SECONDARY
Malignant disease
Drugs
Protein-losing states
Infection (cause & effect)
Systemic disease
Iatrogenic causes
Chromosomal abnormalities
WHAT’S NEW?
• Secondary Antibody Deficiency

• Revision / collation into a single indication
+ review outcomes (infection / hospitalisation)
+ dosing (minimum IgG trough 6 g/L)
RECOMMENDATIONS
• Irreversible hypo-
• Hypo- associated with CLL/NHL/MM etc.
and
GUIDELINES
‘Systematically developed statements to assist practitioner
and patient decisions about appropriate health care for
specific clinical circumstances’
•
•
•
•
•
Evidence-based use
Consistency of care
Access to safe, high quality products
Security of supply
Utilising scarce resource
OUTCOMES
COMPLICATIONS
PROGRESSION OF COMPLICATIONS
QUALITY OF LIFE
WORKING CAPACITY
LIFE EXPECTANCY
OPTIMISED GROWTH / DEVELOPMENT