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)

RECOMMENDATION / REQUIREMENT 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 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 Evidence-based use Consistency of care ‘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