Comparison of immune reactivity and pharmacokinetics of two hepatitis B immune globulins in patients after liver transplantation

Abstract

Hepatitis B virus (HBV) immune globulin (HBIg) administration will prevent HBV graft reinfection in HBV patients after orthotopic liver transplantation (OLT). However, the expenditure for such prophylaxis is extremely high ranging between $2,000 to $10,000 per month in various countries for an undefined period and presumably for life. As a consequence, there is a need for introduction of additional and less expensive modes of treatment. In a preliminary clinical trial a new HBIg preparation has been shown to induce longer lasting levels of circulating antibodies to hepatitis B surface antigen (anti‐HBs) in patients after OLT compared with previous experience with conventional HBIg preparations. In the present study the pharmacokinetics of this new HBIg, OMRI‐Hep‐B, were studied and compared with a conventional, licensed preparation, Hepatect. Fifteen post‐OLT patients (2‐8 years post‐OLT, 18‐62 years of age, 6 men, 9 women) were treated intravenously with 49 doses of OMRI‐Hep‐B or Hepatect given at least once, alternately, at 10,000 to 14,000 units per injection (≈130 IU/kg body weight). The new HBIg was well tolerated and no adverse effects were observed. Administration of OMRI‐Hep‐B was shown to induce high and long‐lasting levels of circulating anti‐HBs antibodies and greater areas under the curve (AUC) compared with the conventional preparation. Thus, anti‐HBs half‐life was 22 ± 1.3 days for OMRI‐Hep‐B recipients and 13 ± 1.3 days for Hepatect recipients (P < .001). Time to reach trough anti‐HBs levels of 150 mIU/mL was significantly longer after administration of OMRI‐Hep‐B than after Hepatect (79 ± 4.5 and 52 ± 3.8 days, respectively; P < .001). In summary, the pharmacokinetic profile of the new HBIg, and in particular its prolonged elimination half‐life, may reduce the cost of administration by approximately 30% and improve the quality of life of patients by extending the interval between repeated immune globulin injections.