Clinical use of polyvalent immunoglobulins.

Abstract

Intravenous immunoglobulins (IVIG) and subcutaneous (SCIG) are used in treatment of a broad spectrum of diseases. Prepared from the collective plasma of several thousand people, therapeutic immunoglobulin consists mostly of human polyspecific IgG1–4. IgG replacement is the standard therapy for primary antibody deficiencies (PAD) aiming to replace the missing antibodies and thereby to prevent recurrent infections. Replacement therapy generally involves the use of 400–600 mg/kg administered every 3 or 4 weeks5–6. Debate continues regarding the exact timing and the optimal prophylaxis regimen, knowing that the system of care is itself an important determinant of patient outcomes7–8. The use of immunoglobulins as an immunomodulating therapy ranges from transplantation and treatment of autoimmune-haematological diseases to treatment of various neuroimmunological clinical entities9–10. Immunomodulating generally involves the use of 2 g/kg administered over either 2 or 5 consecutive days. US FDA approved IVIGs for the treatment of Primary Immune Deficiencies (PID), immune thrombocytopenic purpura, Kawasaki disease, bone marrow transplantation in patients aged over 20 years, chronic B-cell lymphocytic leukaemia, and paediatric AIDS (Table I). Table I FDA approved indications for the therapeutical usage of polyvalent human immunoglobulins. Similarly, in Italy, the indications for IVIGs treatment include Primary Immune Deficiencies, immune thrombocytopenic purpura, Kawasaki disease, bone marrow transplantation in patients aged over 20 years, chronic B-cell lymphocytic leukaemia and myeloma, paediatric AIDS and Guillain-Barre syndrome, and a new recently introduced indication (Table II). Table II Italian approved indications for the therapeutical usage of polyvalent human immunoglobulins. In addition to its use in primary and secondary immune deficiencies, many other clinical conditions might benefit from IVIGs therapy, all requiring documentation of contraindications to or a lack of response to conventional therapies according to US FDA (Table III). Some of these other conditions are extremely rare, making randomised controlled investigations difficult. Randomised clinical trials are warranted to support the evidence-based use of IVIg, and to identify the ideal administration protocols to maximise the benefits of what is a limited resource, knowing that many health care delivery systems are subjected to economic pressures and that individualised medicine and personalised health research presents methodological challenges11. Table III Clinical conditions that might benefit from immunoglobulin treatment according to Food and Drugs Administration additional approved indications with criteria. In this review we first discussed the issue of substitution treatment in primary antibody deficiencies, the choice of the immunoglobulin dosages, timing and the impact of therapy in survival. Then we discussed the immunoglobulin anti-inflammatory and immuno-modulating results in the treatment of immune-mediated demyelinating diseases, of rheumatological diseases (vasculitis and autoimmune connective tissue diseases), of haematological diseases (autoimmune cytopenias), of dermatological conditions (pemphigus and pemphigoid) and their usage in transplantation. Intentionally we did not address the issue of the off-label immunoglobulin treatments, despite their frequent usage carried on the basis of single case reports or uncontrolled studies.