SAN DIEGO – Prophylactic palivizumab cut the odds of hospitalization for severe respiratory syncytial virus (RSV) infection by about 75% among preterm infants born at more than 29 weeks’ gestational age – even those without congenital heart disease or chronic lung disease, investigators reported.
The finding belies the American Academy of Pediatrics’ recommendation to limit use of the humanized monoclonal antibody to infants born before 29 weeks’ gestation and to children who have other risk factors for severe RSV infection, Dr. Ram Yogev of Ann and Robert H. Lurie Children’s Hospital, Chicago, said in an interview.
“Our results validate the older studies, except this was done in real life,” added lead investigator Dr. Eric Simões of Children’s Hospital Colorado, Aurora, who presented the findings at an annual scientific meeting on infectious diseases.
Dr. Eric Simoes
RSV usually causes mild upper respiratory tract infections, but premature infants and children who have comorbid cardiac or pulmonary disease can develop severe infections of the lower respiratory tract. Weekly palivizumab dosing was 45%-80% effective in preventing RSV-related hospitalizations in clinical trials of these high-risk patients, noted Dr. Simões and his associates.
But in 2014, the American Academy of Pediatrics reviewed the literature and revised its guidance to limit palivizumab to preterm infants born before 29 weeks’ gestation and to infants with comorbid risk conditions. The biologic “has been shown to have a limited effect on reducing RSV hospitalization,” the academy concluded. The update drew criticism from some pediatric infectious disease experts, who contended that AAP cited observational studies that actually contradicted its conclusions.
To further examine the issue, Dr. Simões and associates analyzed data from a multicenter study of high-risk infants and children under the age of 2 years who had been hospitalized with lower respiratory tract infections. Between 2002 and 2006, 849 of these patients had a nasopharyngeal wash or endotracheal aspirate tested for RSV, and 403 were positive. The investigators determined that the odds of a positive RSV test were 58% lower for patients who had received prophylactic palivizumab, compared with patients who had not (95% confidence interval for efficacy, 43%-69%; P less than .0001).
Furthermore, palivizumab was 75% effective against severe RSV disease in preterm patients born at 29-35 weeks’ gestation who were chronologically younger than 6 months and had no congenital heart disease or chronic lung disease, said the investigators. Based on that finding, AAP should reconsider its recommendations on palivizumab, said Dr. Yogev.
“This study should answer some of the issues raised in the AAP recommendations,” added Dr. Simões.
Palivizumab did not prevent hospitalizations for human metapneumovirus (hMPV) infection, which further validated the results on RSV, said Dr. Simões. The test-negative case-control design of the study “cuts out the whole issue of [bias due to] care-seeking behavior,” he added. “But children on palivizumab would be more seriously ill, so how do you correct for that? Traditional methods are based on multivariate analysis, but we used propensity scores.” A goodness-of-fit test showed that this approach controlled for all variables except palivizumab exposure and age greater than 6 months, meaning that only these two factors were significantly protective against RSV infection, he said.
IDWeek marked the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
MedImmune sponsored the original study of hMPV tract infections, from which these data were obtained. Dr. Simões reported having received funding support and consulting fees from MedImmune.