PRIMARY & SECONDARYANTIBODY 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 clinicaloutcome 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 requiringhaemopoietic stem cell transplantation

(HSCT)

Specific antibody deficiency(SAD)

Transient hypogammaglobulinaemia of infancy(THI)

SPECIFIC DISORDERS

DISORDER RECOMMENDATION / REQUIREMENT

GOOD’S 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

ANTIBODYDEFICIENCY

PRIMARY SECONDARY

Malignant diseaseDrugsProtein-losing statesInfection (cause & effect)Systemic diseaseIatrogenic causesChromosomal 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

COMPLICATIONSPROGRESSION OF COMPLICATIONS

QUALITY OF LIFEWORKING CAPACITYLIFE EXPECTANCYOPTIMISED GROWTH / DEVELOPMENT