Efficacy and Safety of IgPro20, a Subcutaneous Immunoglobulin, in Japanese Patients with Primary Immunodeficiency Diseases

Abstract

PurposeIntravenous (IVIG) and subcutaneous (SCIG) immunoglobulin infusions are widely used for the treatment of patients with primary immunodeficiency (PID) worldwide. This prospective, multicenter, open-label, single-arm Phase III study evaluated the efficacy, tolerability, and safety of IgPro20 (Hizentra®; L-proline–stabilized 20 % human SCIG) in adult and pediatric Japanese patients with PID.MethodsPatients received three IVIG infusions at 3–4-week intervals followed by a dose-equivalent switch to weekly SCIG infusions. A 12-week wash-in/wash-out period was followed by a 12-week SCIG efficacy period. The primary efficacy endpoint was the comparison of total serum IgG trough levels during the IVIG and SCIG efficacy periods by calculating the geometric mean ratio (GMR).ResultsThe GMR of IgG trough levels on SCIG versus IVIG was 1.09 (2-sided 90 % confidence interval: 1.06–1.13). No serious bacterial infections were reported. Eleven patients (52.4 %) had infectious episodes with an overall rate of 2.98 infections/patient/year; 7 patients (33.3 %) missed school/work/daycare due to infection (3.48 days/patient/year). Sixteen patients (76.2 %) were treated with antibiotics for an adverse event (AE; 47.6 %) or prophylaxis (23.8 %), resulting in 167.42 days/patient/year of antibiotic use. During SCIG treatment, 24 patients (96.0 %) had 269 AEs (0.461 AEs per/infusion) including local reactions as the most common AE (20 patients, 80.0 %). Local tolerability of IgPro20 was assessed as “very good” or “good” after 85.4 % of SCIG infusions. One patient (4.0 %) experienced a serious AE of moderate severity (bacterial infection) that was considered unrelated to study medication.ConclusionIgPro20 was effective and well tolerated in Japanese patients with PID.

Cost-minimization Analysis of IgPro20, a Subcutaneous Immunoglobulin, in Japanese Patients With Primary Immunodeficiency

“…A Phase III pivotal study of IgPro20 in Japanese patients with PID showed that weekly SCIG treatment with IgPro20 was effective in pediatric and adult patients and was tolerated well. 12 The results obtained concur with those seen in previous European 13 and North American 10 trials of IgPro20, suggesting that SCIG could be an alternative treatment opportunity in Japan. IgPro20 has recently been approved in Japan for the treatment of PID and secondary immunodeficiency.…”

“…The cost-minimization analysis of IVIG and SCIG treatment was based on the fact that the efficacy of these 2 treatments was comparable, as reported previously 10,12,13 and this trial has confirmed that IgPro20 treatment resulted in equivalent serum IgG levels compared with previous IVIG treatment. 12 Cost-minimization analysis is an appropriate approach when alternative therapies have identical outcomes, but differ in costs. 21,22 Cost components that were identical between 2 arms were excluded, and we focused on difference of costs between each arm.…”

“…gov identifier: NCT01199705). 12 This study was designed as a prospective, multicenter, open-label, single-arm study with comparison of clinical outcomes before and after switch to treatment with IgPro20. Patients with PID on IVIG treatment (ambulatory care) were switched to self-infusion of subcutaneous IgPro20 at an equivalent dose.…”

Pharmacokinetics, Safety, and Tolerability of Subcutaneous Immune Globulin Injection (Human), 10 % Caprylate/Chromatography Purified (GAMUNEX®-C) in Pediatric Patients with Primary Immunodeficiency Disease

“…Historically, lifelong treatment of these types of PID with immunoglobulin (Ig) through various routes (e.g., intravenous (IV), subcutaneous (SC), intramuscular) has been wellestablished and has been shown to decrease the incidence of infections in these patients [1][2][3][4][5][6][7][8][9][10]. Moreover, SCIg therapy has been shown through several studies to be effective, safe, and well-tolerated in patients with PID [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]. SCIg therapy may be beneficial for patients who are poor candidates for IVIg, have poor venous access, or have recurrent systemic infusion-related reactions (i.e., headache, fever, chills, or myalgia).…”

“…Particularly with children, difficult venous access can be a barrier to IVIg therapy. The results from several studies have shown that SCIg in children is feasible and safe [14,16,19,[21][22][23][24][25]. It is now generally accepted that repeated SCIg infusions result in lower systemic adverse effects such as headaches and joint pain occurring within 72 h of the SC infusion [9].…”