Efficacy and safety of a new, chromatographically purified rhesus (D) immunoglobulin. Pharmacokinetics of anti-D IgG in pregnant RhD-negative women. Multicentre trial of antepartum low-dose anti-D immunoglobulin.
To study the efficacy, safety, and tolerability of the 300 microg dose of a new chromatographically produced rhesus immunoglobulin (Rhophylac 300) for ante- and postnatal rhesus prophylaxis.
                In an open-label multi-centre study, rhesus D (RhD)-negative women were randomly allocated to receive Rhophylac 300 either intravenously or intramuscularly at the 28th week of gestation and within 72 h after delivery of an RhD-positive child. Serum samples were obtained prior to the antenatal dose and 6-11.5 months after delivery of an RhD-positive child and tested by the indirect antiglobulin test and papain test for anti-D. Safety parameters were assessed in all women who were treated with the study drug.
                Four hundred and thirty two women received the study drug antenatally. No differences were detected in efficacy or tolerability between intravenous and intramuscular administration. Of the 261 women who delivered an RhD-positive child and received rhesus prophylaxis according to the protocol, 248 women returned for follow-up investigations. None of them had detectable anti-D at their last visit. There were no serious adverse events, no cases of infectious disease transmission nor clinically relevant changes in laboratory safety values and vital signs attributable to the study drug.
                The results suggest that Rhophylac 300 given intravenously or intramuscularly is safe and efficacious in preventing rhesus (D) immunisation. To assess the pharmacokinetics of anti-D IgG in pregnant Rhesus D-negative women after intramuscular and intravenous administration of 300 microg of Rhophylac.
                An open, randomised, multicentre study.
                Seven gynaecological practices in Germany.
                Fourteen RhD-negative pregnant women at risk of becoming Rhesus D immunised received study drug at 28th week of pregnancy either by intramuscular or intravenous route.
                Anti-D IgG concentrations of serum samples obtained up to 11 weeks following antenatal Rhesus D prophylaxis were quantified by flow cytometry.
                Mean anti-D IgG concentrations after intravenous and intramuscular administration differed up to seven days post-injection, from two weeks onwards they were comparable to each other. Irrespective of the administration route, anti-D IgG in serum was detectable in all women up to at least nine weeks post-administration.
                The serum concentrations of anti-D IgG measured after administration of Rhophylac were very similar to those obtained with 300 microg of a different anti-D immunoglobulin product. Routine antenatal Rh immunoprophylaxis would substantially increase the use of anti-D Ig in the U.K. As availability of anti-D Ig is one factor influencing a decision to introduce routine antenatal prophylaxis, a trial was undertaken to test the efficacy of a lower dose of anti-D Ig than that used in earlier studies. RhD-negative primigravidae were randomized as controls or recipients of two doses of 250iu of anti-D Ig given at 28 and 34 weeks gestation. Blood samples were tested at delivery and at 6 months postpartum for the presence of immune anti-D, and again later if results were equivocal. Nine (1.5%) out of 595 control patients had immune anti-D at follow-up at 6 months and later; 4 (0.78%) of 513 treated women were immunized. It was concluded that, while two doses of 250iu of anti-D Ig may reduce alloimmunization, they are not as effective as two doses of 500iu in a previous trial.
Anti-D, given within 72 hours after childbirth, reduces the risk of RhD alloimmunisation in Rhesus negative women who have given birth to a Rhesus positive infant. However the evidence on the optimal dose is limited.