Agammaglobulinemia: comorbidities and long-term therapeutic risks

ABSTRACT

Introduction: Intravenous Immunoglobulin preparations have long been used as an effective therapeutic approach to patients with predominant antibody deficiencies. The advent of new manufacturing processes and critical control measures have continuously improved the quality of Immunoglobulin preparations, while reducing the rate of adverse events and maintaining their function. Subcutaneous route of administration is becoming a standard of care for safe use of IgG by self-administration at home.

Areas covered: Literature search was performed through Pubmed and Scopus using the search term: (‘Therapeutics’ OR ‘Immunoglobulins, Intravenous’ OR ‘IVIG’) AND (‘Agammaglobulinemia tyrosine kinase’ OR ‘Bruton type agammaglobulinemia’ OR ‘Agammaglobulinemia’ OR ‘Agammaglobulinemia, Autosomal Dominant’) with literature search.

Expert opinion: Most if not all of the infusion related complications of IVIG can be prevented by closely monitoring the patient, by considering slow infusion and by identifying, and if possible reducing, pre-infusion risk factors such as cardiovascular or renal problems, infections and advanced age and by selecting the safest product accordingly. The choice of IVIG product should be based on patients individual risk factors and, if present, history of previous adverse events with a specific brand. It should be made clear to patients that FDA-approved IVIG brands are not different in efficacy, and patients preference in choice of brand should be considered.

KEYWORDS:

• Agammaglobulinemia
• XLA
• immunoglobulin replacement therapy
• intravenous immunoglobulin
• IVIG

Article Highlights

• Intravenous immunoglobulins remain the most effective preventive therapy in predominant antibody deficiencies such as XLA, autosomal recessive agammaglobulinemia, Hyper IgM syndrome, CVID and in infants with SCID awaiting bone marrow transplantation.

• A significant proportion of immunoglobulin infusion associated adverse events are hazards that are characteristic of infusion of all blood products. Most, If not all, can be prevented by closely monitoring the patient, by considering slow infusion and by identifying, and if possible reducing, pre-infusion risk factors such as cardiovascular or renal problems, infections and advanced age, and importantly, by choosing the safest product for each individual patient.

• Slow infusion rates as well as focusing on patient hydration, premedication and monitoring ensures a safe infusion of IVIG/SCIG.

• While there is no evidence-based difference in efficacy, there are formulation-based differences in complication rates. Choices of the product have to be made based on patient risk factors and preference, product composition, and availability.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded