Efficacy and Safety of a New Intravenous Immunoglobulin Product in Patients with Chronic Immune Thrombocytopenic Purpura.

Abstract

Background Intravenous immunoglobulin (IVIG) is an accepted treatment for immune thrombocytopenic purpura (ITP). A new liquid 10% human IgG preparation stabilized with proline at a pH of 4.8 (trade name: Privigen) was recently developed. It can be stored at room temperature and is therefore always ready to use. Here we report its efficacy and safety in patients with chronic ITP. Patients and Methods Fifty-seven patients with chronic ITP and a platelet count below 20 x 109/L were included in this open-label, single arm, multi-center Phase III trial. IVIG was given at a dose of 1 g/kg on 2 consecutive days at a maximum infusion rate of 4 mg/kg/min. A subset (56.1%) of the patients received premedication (acetaminophen or diphenhydramine) to avoid adverse events. The primary endpoint was the platelet response rate, defined as the percentage of patients showing an increase in platelet count to ≥50 x 109/L within 7 days of the first infusion. Secondary endpoints included platelet counts at specified time points, time to platelet response, duration of platelet response, and regression of hemorrhages at different bleeding sites. Safety was evaluated by the frequency and severity of adverse events. Results The primary endpoint, an increase in platelet counts to ≥50 x 109/L, was achieved by 81% of the subjects (95% CI: 69–89%). The highest median platelet count (149 x 109/L) was observed on day 8. Median time to response was 2.5 days, with 43% of subjects responding within 1 day. Median duration of platelet response (days with platelet count ≥ 50 x 109/L) was 15.4 days. Regression rates for various bleeding sites ranged from 78% to 100%. Regression of bleeding correlated with increases in platelet counts. Adverse events were reported in 52 (91%) subjects. The most common adverse event was headache (67%), the incidence and severity of which was attenuated by premedication with acetaminophen/diphenhydramine. There were 3 serious adverse events, one of which (aseptic meningitis) was considered related to the study medication. Conclusions The present study has shown the safety and significant efficacy of a novel, 10% liquid, ready for use IVIG preparation, in patients with chronic ITP. A rapid increase in platelet counts to a level where severe bleeding episodes become more unlikely was seen in the majority of patients, as expected with IVIG given at 1 g/kg on 2 consecutive days. The increase in platelet counts was associated with a regression of bleeding. Adverse events were generally mild to moderate in severity, corresponded to those expected with IVIG, and could be prevented with premedication.