Correspondence

Immunoglobulin replacement therapy: Is there a role for IgA and IgM?

Colonel Ogden Bruton reported X-Linked Agammaglobulinaemia in 1952 and treated the child with replacement immunoglobulin therapy. Over 60 years later, the treatment for XLA has largely remained unchanged. Replacement immunoglobulin lacks the isotypes IgA and IgM, leading to concerns that patients continue to experience recurrent sinopulmonary tract infections and be at increased risk of bronchiectasis. There is potential hope of earlier diagnosis with newborn screening, and a potential cure for these patients, in the form of gene therapy. However, it is first necessary to evaluate current management and outcomes to aid decisions regarding further research and clinical trials. This article reviews current management and outcomes of XLA, whilst identifying gaps in our knowledge base that may need answering before we proceed with novel diagnostic methods and treatment for XLA.

The increasing therapeutic use of intravenous immunoglobulin (IVIG) for an expanding range of indications, from immunodeficiency to autoimmune disease coupled with the availability of multiple products has prompted debate on whether IVIG products should be considered to be generic. Although the manufacturing process and associated excipients for individual products varies, all currently licensed IVIG products are composed predominantly of IgG (>95%) and comply with the quality standards of regulatory agencies. Because these products have a licence for a common group of indications, does that mean that all of them are equally efficacious in the treatment of the same disease? In vitro data and published evidence of head-to-head trials of IVIG in primary antibody deficiency, immune thrombocytopenic purpura, and chronic inflammatory demyelinating polyneuropathy suggest that different IVIG products are likely to be equally efficacious in terms of clinical efficacy. Consequently, it would be reasonable to consider IVIG products to be generic in terms of clinical outcomes. However, the lack of significant differences in clinical efficacy should not be used to justify frequent product changes on financial or nonclinical grounds because of the increased risk of adverse effects and difficulty in tracking a suspect product in the event of a future outbreak of IVIG-associated viral transmission.