Switching Patients With Primary Immunodeficiency Disease to Hizentra May Reduce Costs

During a science and innovation theater at the AMCP 2017 Annual Meeting, Girishanthy Krishnarajah, MPH, PhD, senior director of global health economics and reimbursement at CSL Behring, presented data showing that switching patients to 20% Hizentra (subcutaneous globulin immunoglobulin; CSL Behring) at equivalent dose ratios could decrease costs among patients with primary immunodeficiency disease.

“Immune Globulin Subcutaneous (Human), Hizentra, is indicated as replacement therapy for patients with primary humoral immunodeficiency, age 2 and older,” Dr Krishnarajah said during his presentation. “This includes but is not limited to the humoral immune defect in congenital agammaglobulinemia, common variable immunodeficiency, X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.”

Dr Krishnarajah explained that primary immunodeficiency disease encompasses over 200 rare genetic diseases. She cited data showing that the prevalence rate of primary immunodeficiency disease is an estimated 1 in every 1200 people in the United States. 

Primary immunodeficiency disease is characterized by multiple symptoms, including recurrent or difficult-to-treat infections, poor growth or weight loss, recurrent deep abscesses of the organs or skin, and swollen lymph glands or an enlarged spleen. Dr Krishnarajah stated that the increased susceptibility to infections is caused by a compromised immune system. 

The cost and utilization burden of primary immunodeficiency disease is high, Dr Krishnarajah explained, caused mostly by high hospitalization rates. According to the presentation, the average primary immunodeficiency disease patient has 5 annual days of hospitalization and 12 annual provider, emergency department, or hospital visits. Yearly costs associated with infection are estimated to be $18,368 per patient. Dr Krishnarajah added that more than 50% of patients with immunodeficiency disease also have antibody deficiencies, which can increase complications and the risk for comorbid disease. 

Normally, immunoglobulin G (IgG) replacement therapy is administered intravenously or subcutaneously—with equivalent efficacy regarding infection prevention observed for both methods. However, Dr Krishnarajah noted that subcutaneous administration decreases rates of systemic adverse reactions and has easier patient access because it can be self-administered as opposed to physician-administered. Along with reduced administration costs, subcutaneous IgG also reduced costs through fewer school or work days missed. She cited data showing that switching from intravenous administration to subcutaneous administration could save between $755 and $4115, per patient per year. 

Dr Krishnarajah said that Hizentra is the first 20% subcutaneous IgG therapy approved by the FDA to treat patients with primary immunodeficiency disease. Hizentra is also convenient because it can be self-administered and can be stored at room temperature. 

Is There a Need For Dose Adjustment?

When switching from intravenous IgG to subcutaneous IgG, patients should have increased doses in order to ensure equivalent systemic exposure. Hizentra is recommended at a 1.37 times higher dose in the United States; however, in Europe Hizentra is considered equivalent at the same dose. Dr Krishnarajah suggested that this calls into question the need for dose adjustment coefficients in the United States. 

In order to study the need for dose adjustment coefficients, Dr Krishnarajah and colleagues observed real-world Hizentra dose ratios after patients switched to subcutaneous administration. They retrospectively examined shipment data from specialty pharmacy and service providers from 2011 to 2016. Dose ratios at 2 to 4 months, 4 to 6 months, and 6 to 8 months were compared to the initial dose ratios at initiation to 2 months. 

Dr Krishnarajah and colleagues found that median dose ratios for Hizentra during the later months were significantly different from the median dose ratio at the initial months after switch (P < .001). The researchers noted that dose ratios decreased from 1.14 times their intravenous dose at 2 months to 1.05 times at 8 months.

“This study indicates that US patients switching from intravenous IgG to 20% Hizentra begin treatment at doses lower than the current US-recommended 1.37 to 1 dosing ratio,” Dr Krishnarajah said. “Dose ratios at later intervals demonstrate that patients actually receive a dose nearly equivalent to their intravenous dose, as is recommended in the European Union.”

Dr Krishnarajah suggested that eliminating the need for 1.37 times the dose for Hizentra, and using it at an equivalent dose could be both cost-saving and cost-effective. 

“Real-world data indicate a post-conversion dose ratio that is approximately 1 to 1, which could indicate a potential cost savings associated with subcutaneous IgG,” Dr Krishnarajah concluded. “Potential implications of the lower, real-world dose ratio include reduced direct and indirect costs.” 

Dr Krishnarajah’s research was funded by CSL Behring. —David Costill