Palivizumab prophylaxis of respiratory syncytial virus disease from 1998 to 2002: results from four years of palivizumab usage.

OBJECTIVES

In 1998 the Food and Drug Administration approved palivizumab (Synagis) for the prevention of severe lower respiratory tract infection secondary to respiratory syncytial virus (RSV) in pediatric patients at high risk for developing disease that required hospitalization. In the immediate aftermath of that approval, two retrospective reviews were conducted on 4669 medical records of patients who received at least 1 dose of palivizumab during the 1998 to 1999 and 1999 to 2000 RSV seasons, respectively. These analyses captured data on rates of RSV hospitalization, length of hospital stay, intensive care unit admission and compliance with palivizumab administration. Two prospective US multicenter registry trials followed, during the RSV seasons of 2000 to 2001 and 2001 to 2002. The registries characterized the demographics and outcomes of a total of 7207 high risk infants and children who received prophylaxis for RSV, the risk factors for RSV hospitalization and the patterns and scope of palivizumab usage across 63 and 116 US health care sites, respectively. 1998 TO 1999 PALIVIZUMAB FIRST SEASON OF GENERAL USE: Nine US study sites engaged in a retrospective chart review of infants and children with a gestational age of < or =35 weeks and a chronologic age of <2 years at the time of their first palivizumab injection and who had received at least one dose between September 1998 and May 1999. Of the 1839 prophylaxed children with evaluable data, only 42 (2.3%) were hospitalized with confirmed RSV disease. Of those admitted with confirmed gestational ages, all were premature; the majority were either < 28 weeks gestational age (WGA; 43%) or between 28 and 32 WGA (34%). 1999 TO 2000 PALIVIZUMAB SECOND SEASON OF GENERAL USE: During the 1999 to 2000 RSV season, 12 hospitals and university medical centers, representing a cross-section of US health care facilities, contributed to the second Palivizumab Study Group. The sites collected retrospective data from the charts of 2830 children, all of whom had received at least 1 injection of palivizumab between September 1999 and May 2000. Analysis of 2830 medical records revealed an admission rate of 2.4% (68 of 2830) for confirmed RSV infection, consistent with the overall hospitalization rate of 2.3% from the previous season.

PALIVIZUMAB OUTCOMES REGISTRY

2000 to 2001: Sixty-three sites representing pediatric offices, freestanding clinics and hospital-based clinics participated in a prospective, multicenter, observational study to evaluate the scope of palivizumab usage in a cross-section of US infants. The centers collected outcomes data on RSV-related hospital admissions, injection history and adherence to a standardized palivizumab administration protocol. Of the 2116 infants enrolled 47% were born at < 32 weeks gestation. Patients between 32 and 35 weeks gestational age accounted for another 45% of enrollees. Approximately 8% had a gestational age of >35 weeks. For the 2049 subjects with available follow-up data, the overall confirmed RSV hospitalization rate was 2.9%.

PALIVIZUMAB OUTCOMES REGISTRY

2001 to 2002: Between June 1, 2001 and May 15, 2002, 116 health care centers across the US enrolled 5091 infants in the second prospective Palivizumab Outcomes Registry. As its primary outcome the study measured the occurrence of RSV hospitalization with secondary variables of risk factors for RSV bronchiolitis and compliance with the projected number of palivizumab injections based on month of initial dose. Forty-nine percent (n = 2,501) of the infants were born between 32 and 35 weeks gestational age, 40% (n = 2020) were born at a gestational age of <32 weeks and 11% (n = 570) were born at >35 weeks gestational age. Nineteen percent (n = 964) of these children were deemed at sufficient risk to warrant palivizumab prophylaxis for a second season. Seventy-six of 5084 enrolled subjects experienced a total of 78 RSV-related hospital admissions, for an overall hospitalization rate of 1.5%. Four years of retrospective and prospective data on the use of palivizumab in clinical practice has accumulated a wealth of "real life" information on the clinical effectiveness of RSV immunoprophylaxis in a large cohort of high risk infants from geographically diverse pediatric offices and clinics throughout the United States.