PubMed2003
BACKGROUND AND OBJECTIVES: A nanofiltration step with the capacity to reduce blood-borne pathogens was introduced into the manufacturing process of intravenous immunoglobulin (IVIG). In order to demonstrate the efficacy, safety and pharmacokinetics of the modified product, we conducted Phase II/III studies comparing the nanofiltered IVIG (IVIG-N) with its parent product, Sandoglobulin, in patients with chronic immune thrombocytopenic purpura (ITP) and primary immunodeficiencies (PID). MATERIALS AND METHODS: Patients with ITP (n = 27) with platelet counts of < 20 x 10(9)/l were treated with Sandoglobulin or IVIG-N infusions at a dose of 0.4 g/kg body weight on five consecutive days. The primary efficacy end-point was the number of patients with an increase in platelet counts to > 50 x 10(9)/l. Secondary end-points were time to and duration of response, and regression of bleeding. Patients with PID (n = 36) were treated for 6 months with Sandoglobulin or IVIG-N at doses of 0.2-0.8 g/kg, infused at 3- or 4-week intervals. The primary end-point was the number of days absent from school/work. Secondary end-points were hospitalization, use of antibiotics and feeling of well-being. In both studies, tolerability was assessed by recording of adverse events and laboratory determinations. Viral safety was ascertained by serology supplemented with nucleic acid detection methods. Pharmacokinetics were analysed in patients with PID using serum concentration-time data for immunoglobulin G (IgG), and IgG antibodies to hepatitis B surface antigen (anti-HBsAg). RESULTS: In the ITP study, the primary end-point was met by 12/16 patients on IVIG-N and by 10/10 patients on Sandoglobulin (P = 0.123). A shift towards lesser bleeding intensity was seen in both groups. In the PID study, seven of 18 patients on IVIG-N and six of 16 patients on Sandoglobulin missed days at work/school, with monthly mean absences of 0.4 and 0.5 days (P = 0.805). The feeling of well-being was comparable in both groups. In the ITP study, adverse events with a causal relationship to medication were suspected in six patients on IVIG-N and in seven on Sandoglobulin. In the PID study, three patients on IVIG-N and two on Sandoglobulin experienced possible drug-related adverse events. In both studies, serological and polymerase chain reaction (PCR) tests gave evidence for virus safety. Pharmacokinetics showed constant peak and trough serum IgG levels in all patients, indicating almost steady-state conditions for both formulations. The overall half-life (t1/2) for total IgG was 33 +/- 17 days in the IVIG-N arm and 25 +/- 16 days in the Sandoglobulin arm; for anti-HBsAg t1/2, values were 17 +/- 7 and 17 +/- 9 days, respectively. CONCLUSIONS: IVIG-N is efficacious, well tolerated and safe in patients with ITP and PID. Its pharmacokinetic properties were comparable to those of Sandoglobulin.