Long-Term Efficacy and Safety of Hizentra® in Patients with Primary Immunodeficiency in Japan, Europe, and the United States: a Review of 7 Phase 3 Trials

Abstract

Many patients with primary immunodeficiency (PID) require immunoglobulin G (IgG) replacement therapy, delivered as intravenous IgG (IVIG) or subcutaneous IgG (SCIG). We aim to identify trends in efficacy and safety that would not be evident in individual studies of small patient numbers. Seven open-label, Phase 3, prospective, multicenter studies of the efficacy and safety of Hizentra® (a SCIG), conducted in Japan, Europe, and the US were summarized. Overall, 125 unique patients received 15,013 weekly infusions during a total observation period of 250.9 patient-years. Mean weekly doses of Hizentra® were 83.22-221.3 mg/kg body weight; infusion rates per patient (total body rate) were 25.2-49.3 mL/h across studies. The rates of infections and serious bacterial infections were 3.10 and 0.03 events per patient/year, respectively. Annualized rates of days hospitalized due to infection, out of work/school, and prophylactic antibiotic use were 0.95, 5.14, and 36.78 per patient, respectively. For the equivalent monthly dose, weekly Hizentra® SCIG administration resulted in expectedly-increased serum IgG trough levels in patients switching from IVIG, and maintained levels in patients switching from previous SCIG. Adverse events (AEs) totaled 5039 (events/infusion 0.094-0.773), almost all of which were mild/moderate. Three thousand one hundred ninety-seven were considered treatment-related, the most common of which were injection site reactions (2919 events; 0.001-0.592 AEs per infusion). Systemic AEs were very uncommon. The results from these seven studies indicate that Hizentra® therapy was both efficacious and well tolerated during long-term treatment. This is particularly important in patients with PID, who may require lifelong IgG replacement therapy.

Keywords: IVIG; Immunoglobulin G replacement therapy; SCIG; primary antibody deficiencies; primary immunodeficiencies.

Fig. 1

Study duration. AT all treated, ITT intention-to-treat, MITT modified intention-to-treat, PPS per protocol set

Fig. 2

Summary of infections, days hospitalized due to infection, and use of antibiotics for infection prophylaxis. Annualized rates of infections and antibiotic use for prophylaxis are calculated from the number of study days; annualized days hospitalized due to infection are calculated from the number of patient diary days. AT all treated, ITT intention-to-treat, MITT modified intention-to-treat, PPS per protocol set

Fig. 3

Frequency of infections per calendar month. The frequency of infections per calendar month was analyzed using a logistic regression model based on a Poisson distribution

Fig. 4

Summary of AEs (a) and SAEs (b). AE adverse event, AT all treated, ITT intention-to-treat, SAE serious adverse event