A Multicentre Study on the Efficacy, Safety and Pharmacokinetics of IqYmune\xae, a Highly Purified 10% Liquid Intravenous Immunoglobulin, in Patients with Primary Immune Deficiency

Gergely Krivan,Alain Sadoun,Ewa Bernatowska,Anne Bellon,Zoltan Nyul,Larysa Kostyuchenko,Martin Kappler,Beata Derfalvi,Ludmila Chernyshova,Jacek Musial,Andrzej Lange

doi:10.1007/s10875-017-0416-4

Abstract

This multicentre, open-label, prospective, single-arm study was designed to evaluate the efficacy, pharmacokinetics, and safety of IqYmune®, a highly purified 10% polyvalent immunoglobulin preparation for intravenous administration in patients with primary immunodeficiency. IqYmune® was administered to 62 patients (aged 2–61 years) with X-linked agammaglobulinemia or common variable immune deficiency at a dose from 0.22 to 0.97 g/kg every 3 to 4 weeks for 12 months with an infusion rate up to 8 mL/kg/h. A pharmacokinetic study was performed at steady state between the 8th and the 9th infusion. A single case of serious bacterial infection was observed, leading to an annualized rate of serious bacterial infections/patient (primary endpoint) of 0.017 (98% CI: 0.000, 0.115). Overall, 228 infections were reported, most frequently bronchitis, chronic sinusitis, nasopharyngitis and upper respiratory tract infection. The mean annualized rate of infections was 3.79/patient. A lower risk of infections was associated with an IgG trough level > 8 g/L (p = 0.01). The mean annualized durations of absence from work or school and of hospitalization due to infections were 1.01 and 0.89 days/patient, respectively. The mean serum IgG trough level before the 6th infusion was 7.73 g/L after a mean dose of IqYmune® of 0.57 g/kg. The pharmacokinetic profile of IqYmune® was consistent with that of other intravenous immunoglobulins. Overall, 15.5% of infusions were associated with an adverse event occurring within 72 h post infusion. Headache was the most common adverse event. In conclusion, IqYmune® was shown to be effective and well tolerated in patients with primary immunodeficiency.

Highlights

Primary immunodeficiencies (PIDs) are a heterogeneous group of inherited diseases predisposing individuals to6 2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary10 Immunology Clinic Department, Children’s Memorial Health Institute, Warsaw, PolandJ Clin Immunol (2017) 37:539–547 increased risk of infection
The present study investigated the efficacy, pharmacokinetics, and safety of IqYmune® in paediatric and adult patients with X-linked agammaglobulinemia (XLA) or common variable immune deficiency (CVID)
The main exclusion criteria were history of allergy or serious adverse reaction to Ig therapy, anti-IgA antibodies, glomerular filtration rate (GFR) 2 times upper limit of normal, protein-losing enteropathy or nephrotic syndrome, history of thrombosis within the past 12 months, pregnancy, and breastfeeding

Summary

Introduction

6 2nd Department of Paediatrics, Semmelweis University, Budapest, Hungary. 10 Immunology Clinic Department, Children’s Memorial Health Institute, Warsaw, Poland. Most types of PIDs are associated with a hypogammaglobulinemia due to impaired antibody production. Chronic or recurrent upper and lower respiratory tract infections, sinusitis, and otitis media are the most common infections, while severe bacterial infections (SBIs) such as sepsis, meningitis, septic arthritis, and osteomyelitis can occur [2,3,4]. In the absence of early diagnosis and appropriate therapy, recurrent respiratory infections eventually lead to the development of bronchiectases and other chronic pulmonary diseases [5, 6]. Immunoglobulin (Ig) replacement is the mainstay of therapy for PID patients with hypo- or agammaglobulinemia. X-linked agammaglobulinemia (XLA) and common variable immune deficiency (CVID) are the most common forms of PIDs requiring Ig replacement therapy [9, 10]

Methods

Results

Conclusion