Safety of IGIV therapy and infusion-related adverse events.

Patients with primary immunodeficiency diseases have been treated with intravenous gammaglobulin (IGIV) for over 20 years. Gamma globulins were first introduced as a therapeutic modality in 1952 by Robert A. Good, who injected gamma globulins by the intramuscular (IM) route to treat patients with X-linked agammaglobulinemia. Subsequently, the clinical indications for gamma globulins therapy expanded from patients with Bruton's disease and other primary immune deficiency disorders to include a variety of autoimmune and inflammatory diseases. This expansion in clinical indications paralleled two critical steps in the development of gamma globulins preparations. First, proteolytic enzyme-treated immunoglobulins became available for intravenous (IV) administration; unlike earlier IM preparations, IV preparations could be administered in larger volumes, were less painful, rapidly achieved physiologic concentrations of serum IgG, and were similar to native immunoglobulins with respect to their distribution of IgG subclasses and their pharmacokinetic features. Newer, highly purified IGIVs also became available. Second, significant efforts have been made to enhance the viral safety of IGIVs. Manufacturers no longer depend on Cohn-Oncley or cold ethanol treatment as the only viral elimination step; rigorous donor screening, plasma testing by sensitive nucleic acid testing, and additional viral inactivation steps in the manufacturing processes for IGIVs have been implemented. In spite of the fact that this therapy has been life-saving in patients with primary immunodeficiency diseases, a number of adverse events have been reported as a result of its use. This paper will review some of the more frequent and important adverse events associated with the administration of IGIV, and discuss the mechanisms by which these reactions may occur. Our approach for replacement therapy with IGIV of patients with primary immunodeficiency diseases will be described, and some of the concerns related to the availability of commercial IGIV for this important patient population will be presented. Availability of IGIV product has been of particular concern to the clinical immunologists who take care of patients with primary immune deficiency disorders since there are no alternative therapies for these patients.