Prospective open-label study of pharmacokinetics, efficacy and safety of a new 10% liquid intravenous immunoglobulin in patients with hypo- or agammaglobulinemia

Background and Objectives The aim of this study was to evaluate the pharmacokinetics, efficacy and safety of a newly developed 10% liquid immunoglobulin preparation in patients with primary immunodeficiency diseases. This new preparation for intravenous use includes three dedicated virus clearance steps in its manufacturing process to ensure a high margin of viral safety. Materials and Methods This was a prospective, open-label, non-controlled, multicentre study. Twenty-two subjects with primary immunodeficiency were treated initially with three infusions of a licensed intravenous immunoglobulin to standardize the immunoglobulin G (IgG) replacement therapy of all subjects to the same intravenous product. A total of nine infusions of the new 10% liquid preparation were subsequently administered. Results The median terminal half-life of total IgG following administration of the new preparation was 30.1 days. Median terminal half-lives for IgG subclasses IgG(1), IgG(2), IgG(3) and IgG(4) were 28.3, 31.3, 20.9 and 24.2 days, respectively. The median total serum IgG steady-state trough level was 8.51 g/l. No severe infection episodes started after initiation of treatment with the new preparation. The median rate of mild or moderate infection episodes was 0.48 per month. A total of 194 infusions with the new 10% liquid immunoglobulin preparation were administered. The mean dose per infusion was 0.41 g/kg body weight and the maximum infusion rates recorded were 8 ml/kg/h. Adverse experiences were mostly mild and unrelated to the study drugs. Only 4% of infusions with the new product were followed by one or more related adverse experiences. Conclusion The new 10% liquid immunoglobulin preparation was well tolerated and shown to have an excellent pharmacokinetic, efficacy and safety profile. The liquid formulation provides convenience to patients and healthcare professionals

Quality of life, physical function and MRI T2*in elderly low-risk MDS patients treated to a haemoglobin level of >= 120 g/L with darbepoetin alfa +/- filgrastim or erythrocyte transfusions

Objective: Anaemia in low-risk MDS is associated with reduced quality of life (QoL). Response to treatment with erythropoietin (EPO) + G-CSF is associated with improved QoL, but whether transfusion therapy with higher haemoglobin (Hb) target levels has similar effects is unknown. The objective for this prospective phase II Nordic multicentre trial was to assess QoL, response rate and physical function in elderly anaemic MDS patients treated to a target Hb level of >120 g/l. Methods: Thirty-six elderly low- and intermediate-1 risk MDS patients received darbepoetin (DA) 300μg/week, with the addition of G-CSF if no response. If the Hb target was reached at 16 weeks, treatment was maintained until week 26. Remaining patients were transfused to reach the target level for at least 8 weeks. Results: Twenty-seven patients completed the study. Response rate to DA±G-CSF was 67% in evaluable patients and 56% according to intention-to-treat. Eighteen patients reached the target Hb level according to protocol. QoL scores for fatigue, dyspnoea, constipation, and physical, role and social functioning improved significantly during study, with similar results for transfused and untransfused patients. Maintaining Hb > 120 g/L did not confer a higher transfusion rate, once the target was reached. In two of fourteen patients MRI T2* indicated cardiac iron overload, however without association with ferritin levels. Conclusions: In elderly anemic MDS patients an increment in haemoglobin is associated with improved QoL, whether induced by growth factor treatment or transfusion therapy