Author(s): Bohumír Blazek aff1 , Siraj A Misbah aff2 , Pere Soler-Palacin aff3 , Barbara McCoy aff4 , Heinz Leibl aff4 , Werner Engl aff4 , Victoria Empson aff4 , David Gelmont aff5 , Nikolai Nikolov [*] aff6
autoimmune disease; GAMMAGARD LIQUID; immunodeficiency; intravenous immunoglobulin; KIOVIG
Replacement therapy with human plasma-derived polyclonal immunoglobulin (Ig) concentrates (administered at doses of 0.2-0.8 g/kg/month) is a life-saving treatment that has long been established as the standard of care in patients with primary immunodeficiency diseases (PID) [1,2 ]. In addition, replacement therapy with human Ig plays an important role in the management of patients with secondary antibody deficiency arising from hematological malignancies (e.g., chronic lymphocytic leukemia and multiple myeloma, which are licensed indications for Ig replacement) or their treatment [2-6 ]. At high doses of 1.0-2.0 g/kg/month, Ig is also used for immunomodulation which has become an essential treatment in many autoimmune conditions. Immunomodulation has been shown to be safe and efficacious for a wide array of autoimmune diseases in which effective alternative therapies are often lacking, including thrombocytopenic purpura (ITP), Guillain-Barré syndrome, Kawasaki syndrome, multifocal motor neuropathy and chronic inflammatory demyelinating polyneuropathy, which are recognized as established indications for Ig therapy [2,6-9 ].
The mechanism by which Ig regulates the disordered immune response in autoimmune disease has not yet been fully elucidated. Pleiotropic actions of Ig on the effector cells and noncellular components of both innate and adaptive immunity are proposed, and have been described previously [ 2,10-15 ]. Moreover, the clinical evidence base in some of these indications is limited due to the difficulty in conducting randomized clinical studies on diseases that are rare or heterogeneous [8,16-17 ]. Data collected from patient registries and prospective noninterventional studies can assist in confirming the safety profile and characterizing the therapeutic outcomes of Ig treatment in a real-world setting [18,19 ]. In this postauthorization safety surveillance study, the safety, tolerability and efficacy of a virus-inactivated, 10% liquid preparation of Ig for intravenous administration was investigated in patients with immunodeficiency or autoimmune diseases.
Patients & methods
Human normal immunoglobulin 10% liquid (Baxter Healthcare Corporation, licensed as GAMMAGARD LIQUID® in the USA and KIOVIG® elsewhere, hereafter referred to as intravenous immunoglobulin 10% [IVIG 10%]), is a highly purified preparation of functionally intact Ig derived from large pools of human plasma with three dedicated virus clearance steps. IVIG 10% is supplied as a ready-to-use liquid formulation, stabilized with glycine (0.25 M) and formulated without added sugars, sodium or preservatives. The average concentration of IgA in IVIG 10% is 37 µg/ml. The pH is 4.6-5.1, and the osmolality is 240-300 mOsmol/kg. IVIG 10% was stored in a refrigerator (2 -8°C), protected from light.
Patients requiring treatment for diseases for which IVIG 10% held marketing approval were enrolled in this postauthorization safety surveillance study. Prior to enrollment, patients or their parent/legally authorized representative provided written informed consent, and were informed that their medical records would be accessed and transferred to the sponsor. The following additional inclusion criteria were applicable: the patient had been prescribed IVIG 10% for...