February 1996
GAITHERSBURG, Md.—The Food and Drug Administration has approved an intravenous immune globulin preparation to prevent respiratory syncytial virus (RSV) infections in some children.
The product promises to give pediatricians, for the first time, a way to prevent RSV infection in children whose underlying medical conditions put them at risk for serious RSV infections. The FDA approved intravenous RSV immune globulin (RSVIG) for RSV prophylaxis in children aged 24 months or younger with bronchopulmonary dysplasia (BPD) or who had been born prematurely.
RSV is associated with an estimated 90,000 hospitalizations and 4,500 deaths from lower respiratory tract disease annually. Infants with severe RSV disease are typically treated with supplemental oxygen and hydration. Ribavirin is the only licensed antiviral drug to treat RSV.
MedImmune, Inc., based here, is marketing the product. Massachusetts Public Health Biologic Laboratories, Boston, makes RSVIG for MedImmune.
At a December 1995 meeting, the FDA's Blood Products Advisory Committee agreed to recommend that the FDA approve the drug for use in these high-risk children. Two years ago, the same committee voted not to recommend that the FDA approve the drug. Committee members had criticized certain aspects of the first clinical trial, which was conducted in Denver, Washington, D.C., Cleveland, and Buffalo, N.Y. For example, some members expressed concern that patient assignment to treatment and control groups was not blinded and thus was open to potential bias. In addition, some committee members believed that study conclusions relied too heavily on the clinical experience at Denver, where, compared with the other sites, researchers reported a significantly higher incidence of RSV-related lower respiratory tract infections and a much greater treatment efficacy.
MedImmune then conducted another multicenter trial, this time ensuring that assignments to treatment or control groups were blinded and randomized and that no one site dominated study data.
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The first trial, which spanned three RSV seasons, found that RSVIG had a low adverse effect profile similar to that of other immune globulins. Out of 580 total infusions, 97% were associated with no adverse reactions. The trial found that RSVIG reduced the incidence of hospitalizations for RSV by 57%, reduced the number of days in the hospital by 53%, and reduced the number of days in the intensive care unit by 97%. Data gathered from this trial were published in the New England Journal of Medicine in November 1993.
The second trial was completed this past May. It was a single-season, double-blind, placebo-controlled study that enrolled 510 patients at 54 centers nationwide, of which 97% were born prematurely (35 weeks of gestation or less). The trial had two arms: one arm consisted of 250 patients randomly assigned to receive 750 mg/kg of RSVIG and another arm that consisted of 260 patients randomly assigned to receive 1% albumin placebo.
To be included, children needed to have BPD and to have required supplemental oxygen within the past 6 months. Participants were 24 months old or younger at the time of randomization. The two study groups were similar with respect to age at entry into the trial, race, gender, previous contact with RSV, gestational age, and mean birth weight.
Each patient received monthly infusions during the RSV season to a total of 5 infusions.
Although prematurity places children at higher risk for severe RSV disease and RSVIG prophylaxis can lower their risk for severe RSV disease, Leonard Krilov, MD, a pediatric infectious disease specialist who has used RSVIG, said he would not give RSVIG prophylaxis to all preterm children because it is expensive and cumbersome to give.
Children must receive monthly intravenous infusions that can take a half day, and this is not without some risks, said Krilov, who is Chief of Pediatric Infectious Disease at North Shore University Hospital, Manhasset, N.Y.
Consequently, Krilov would shy away from RSVIG prophylaxis in premature children without significant lung disease, he said. He would consider RSVIG prophylaxis, however, in a child born at 27 weeks' gestation and had been on a ventilator for 3 months before going home, for instance.
RSVIG prophylaxis may have a place in protecting some highly immunodeficient children from severe RSV disease, he said.
| Percentage of patients with RSV-related hospitalizations | Days of RSV-related hospitalizations/100 children | |
|---|---|---|
| 13.5 | 129 |
| 8.0 | 60 |
| 41 | 53 |
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