Subcutaneous immunoglobulin replacement therapy with Hizentra®, the first 20% SCIG preparation: a Practical approach
S. Jolles J. W. Sleasman
0
0
S. Jolles Department of Medical Biochemistry and Immunology, University Hospital of Wales
, Cardiff,
UK
1
) Department of Pediatrics, University of South Florida
To reduce the risk of infection in adults and children with primary immunodeficiencies, replacement therapy with IgG, which can be administered to patients intravenously or subcutaneously, is required. Although intravenous administration of IgG (IVIG) has been the therapy of choice in the US and widely used in Europe for many years, subcutaneous administration of IgG (SCIG) has recently gained considerable acceptance among patients and doctors. SCIG therapy achieves high and stable serum IgG levels, is well tolerated, and can be self-administered. Hizentra (IgPro20; CSL Behring, Berne, Switzerland) is the first, ready-to-use 20% liquid preparation of human IgG specifically formulated for subcutaneous infusions. The high concentration (20%) might allow shorter infusion times due to smaller infusion volumes, with potential improvement in the convenience of SCIG therapy. Hizentra is well tolerated and has been shown to protect adult and pediatric primary immunodeficiency patients against serious bacterial infections. In addition, it is easy to handle and can be stored at a temperature up to 25C. In summary, Hizentra is an advance in the field of immunoglobulin replacement therapy, which might offer benefits for home therapy patients.
-
Patients with primary immunodeficiency
(PI) disorders, such as common variable
i m m u n o d e f i c i e n c y ( C V I D ) , X - l i n k e d
agammaglobulinemia (XLA), and autosomal
recessive agammaglobulinemia (ARAG) that
are caused by B-cell dysfunction are prone
to recurrent bacterial infections.1,2 Lifelong
immunoglobulin (Ig) replacement therapy is the
only effective treatment for these patients, and
is thus the gold standard in the management of
primary antibody deficiency.3
IgG can be administered subcutaneously
(SCIG) or intravenously (IVIG) and was first used
by Bruton in a child with agammaglobulinemia in
1952.3 SCIG preparations were introduced in the
1980s in the US and Europe. However, the slow
infusion technique and the low concentration of
the preparations available at the time made SCIG
impractical and less attractive to patients and
healthcare professionals. Therefore, IVIG, which
allowed infusions of higher monthly doses,
became the preferred route of administration.
Despite its success, IVIG may not be suited to
all patients, especially those with poor venous
access. IVIG may be associated with systemic
adverse events (AEs) and IVIG self-administration
is technically more demanding and requires more
training than SCIG self-administration. With
recent technical advances in IgG formulation,
pure and highly concentrated SCIG preparations
that have relatively low viscosity, and can
therefore be infused relatively rapidly, have
been developed and are increasingly used
worldwide.4-6 Usage of SCIG therapy varies greatly
across countries and is predominant in Sweden,
Germany, and the UK (Figure 1).
While IVIG is infused every 3-4 weeks, SCIG is
typically administered once a week, with the total
IVIG monthly dose divided in smaller portions.
The distribution of IgG between the vascular and
extravascular compartments after subcutaneous
administration can be described by a
twocompartment model, which accurately describes
the distribution of serum IgG in healthy individuals
and PI patients (Figure 2).7 In this model, IgG
enters the vascular compartment (blood) from
the extravascular compartment (subcutaneous
space) via the lymphatics at a defined rate, which
integrates IgG catabolism and total IgG distribution.
This model predicts a progressive release of IgG into
the circulation that contributes to the more stable
serum IgG levels achieved with SCIG.
In comparison to IVIG, SCIG results in more
sustained serum IgG levels, avoiding the peaks
and troughs associated with IVIG.6,8 SCIG is
associated with fewer systemic AEs than IVIG
and requires no venous access.4,6,8 Finally, SCIG
is easy to use and is easier to self-administer,
providing patients with flexibility and improved
quality of life.9 Patients treated with SCIG do not
need to go to the hospital or infusion centers,
avoiding unnecessary travel and their potential
concerns for acquiring nosocomial infections.
Patients require less assistance from healthcare
professionals, reducing the cost associated with Ig
replacement therapy, and can take greater control
over their therapy. This review summarizes the
available data on and practical considerations
regarding the use of the subcutaneous 20%
IgG preparation, IgPro20 (CSL Behring, Berne,
Switzerland), currently marketed in the US under
the brand name of Hizentra. Hizentra has a good
safety profile and has been shown to effectively
protect PI patients from serious and non-serious
bacterial infections.10,11
INTRODUCING HIZENTRA
Hizentra is a 20% (200 g/L) ready-to-use
liquid pr (...truncated)