The Evolution of Immunoglobulin Therapy
The history of immunoglobulin therapy dates back to 1952, when concentrated immune human serum globulin was first used to treat an 8-year-old boy with agammaglobulinemia. The advancement of production processes since that time has been accompanied by a much larger safety profile that requires careful management. This and many other issues related to treatment were covered by Autumn Zuckerman, PharmD, BCPS, AAHIVP, and Jonathan Ogurchak, PharmD, CSP, in the session Utilizing Intravenous Immunoglobulin for Immune Disorder Treatment: A Discussion for Specialty Pharmacists, presented at the Asembia Specialty Pharmacy Summit 2018.
This symposium traced the evolution of immunoglobulin therapy from this inception to the state-of-the-art intravenous immunoglobulin products currently employed to manage a wide range of immune disorders.
After a brief review of immunoglobulin structure and function, the presentation turned to the challenges faced in immunoglobulin manufacturing. Starting with plasma collected from up to 10,000 volunteers, intravenous immunoglobulin undergoes fractionation, purification, stabilization, and viral inactivation and removal. The importance of each manufacturing step and its impact on tolerability and safety were discussed.
Immunoglobulin products are administered subcutaneously, intramuscularly, or intravenously. The route of administration affects the pharmacokinetics and pharmacodynamics of immunoglobulins. The presentation examined the unique aspects of each route of administration, including indications, benefits, pitfalls, and appropriateness for specific patient groups.
Selection of an immunoglobulin product must consider patient factors such as renal or cardiac impairment, a history of thrombosis or infusion reactions, and whether the patient has a permanent indwelling catheter. Formulation properties such as infusion volume, sugar and sodium content, osmolality, IgA content, and pH affect tolerability and must be considered in product selection.
The symposium provided specialty pharmacists with a road map to match patient factors with formulation properties when selecting an immunoglobulin product and included an in-depth review of the 12 immunoglobulin products available in the United States.
Notably, the subcutaneous immunoglobulin treatment, Hizentra, was approved in March 2018 by the FDA and represents the first and only subcutaneous immunoglobulin treatment for patients with chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent relapse of neuromuscular disability and impairment.
Data provided for each product covered FDA-approved indications, route of administration, infusion rate, concentration, and formulation properties. Immunoglobulin therapy can be stressful for patients to navigate and may include hurdles such as needle phobia. The symposium ended with a discussion of strategies to minimize common adverse effects, overcome adherence barriers, and improve quality of life.
In clinical trials, between 21% and 50% of patients administered immune globulin intravenous experienced adverse effects, with headache the most common. Rigors, pyrexia, dyspnea, fatigue, nausea, vomiting, and diarrhea were also common. For many of these adverse effects, the symposium noted that decreasing the rate of infusion is the mainstay of management. They can also be managed via pretreatment with antihistamines, acetaminophen, or low-dose corticosteroids. When selecting a product, specialty pharmacists should consider the reputation of the manufacturer, the reliability of the supply, product warranty, and product recalls, according to the symposium.