Clinical insights in immunoglobulin for intravenous (IGIV) therapy

The history of gamma globulin therapy began in the second half of the 20th century as a treatment for pneumonia. Later it was employed as a replacement product for inummodeficient patients, and later still as an immunomodulatory agent. Some of its mechanisms of action are known and others remain to be elucidated; however, its therapeutic effects are thought to be derived through a synergy of mechanisms. Currently immunoglobulin for intravenous (IGIV) therapy is US Food and Drug Administration (FDA) approved for 4 indications. During the past decade, the use of IGIV has grown to such an extent that most of its use is now "off label," and specific recommendations have been made for at least 53 unapproved indications. The value of IGIV therapy as replacement therapy and as an immunomodulatory agent is proved, and its therapeutic effects are in some cases lifesaving. In spite of its significance as a therapeutic agent, very few multicenter, randomized, double-blind, placebo-controlled IGIV clinical trials have been reported. This lack of specific evidence makes product comparisons problematic. Nonetheless, lack of evidence does not mean that an IGIV products are the same. Different manufacturing and purification processes, as well as pharmaceutical formulations, are used to make currently available products. Such formulation-specific characteristics that differentiate these products include volume load, sugar and sodium content, osmolarity, pH, and IgA content. Careful attention to these distinctions in formulation is necessary to ensure optimal IGIV therapy, tolerability of the infusion, and patient care.