Age-dependent Effectiveness of RSV Immunoprophylaxis

1. Age-dependent Effectiveness of RSV Immunoprophylaxis Almut G Winterstein PhD1, 2, Christian Hampp PhD4, Paul Kubilis MS1, ArwaSaidi MBBCh3 1Pharmaceutical Outcomes and Policy, College of Pharmacy, 2Epidemiology, Colleges of Medicine and Public Health & Health Professions, 3Pediatrics, College of Medicine, University of Florida, Gainesville, FL 4Office of Surveillance and Epidemiology, CDER, FDA, Silver Spring, MD, United States Introduction Results Discussion Palivizumab efficacy shows variation between 45 to 78% reduction of hospitalizations for respiratory syncytial virus (RSV) depending on the type of risk-group studied. Based on RSV epidemiology and the risk groups that were targeted in clinical trials current recommendations limit palivizumab utilization to specific age groups. While evidence supports the effect of increasing age on decreasing infection risk, it is unknown whether age modifies palivizumab effectiveness as well. Objectives: To estimate the effect of age on palivizumab effectiveness in preventing RSV hospitalizations in high-risk children. • The analysis included 14,549 children and 21,825 child-seasons. Censoring occurred because of season end (n=9,001), end of eligibility (n=8,889), 2nd birthday (n=3,341), non-RSV hospitalization (n=542), and death (n=52). • ɸ Data cannot be displayed based on CMS requirement to omit cells with <11 observations. • A total of 617 RVS-related hospitalizations occurred during 2,496,942 days of follow-up (90.2 per 1,000 patient-years during season). The six-months mortality of children hospitalized for RSV infections was 4 per 617 hospitalizations (0.65%). • Hazard Ratios for all RSV Risk Factors, Palivizumab Use, and the Interaction between Use and Age • Crude and Adjusted RSV-Risk per Age Stratum • The single most important risk factor for RSV infections was age. With every day of age, RSV risk decreased by 0.34% (95% CI: 0.24-0.44), amounting to 9.66% (6.94-12.30) per month of age. Consequently, children at 6 months of age experience a 34% reduction in RSV risk, 51% reduction at age 9 months, 64% at 12 months, 80% at 18 months and 89% at 24 months, each compared to 2 month old infants (Figure). • Given the age-related decreasing risk and differences in palivizumab effectiveness, numbers needed to treat for the two age strata are as follows: • Age 2-12 months: NNT=34 per 6-months season • Age 13-24 months: NNT=327 per 6-months season • Limitations • RSV hospitalizations may be misclassified as non-specific pneumonia or bronchiolitis. • Residual (unmeasured) confounding may exist. Methods • Study Design • Retrospective cohort study • Data source / study population • Medicaid Extract Files (MAX), Vital Statistics Births and Death Certificates • Children aged 0-2 eligible since birth for Medicaid fee-for-service in TX and FL between 1999-2004 • At least 3 months eligibility between Aug-Mar of any study year • Diagnosis for symptomatic (requiring drug treatment or oxygen) chronic lung disease or hemodynamically significant congenital heart disease based on in- or outpatient and pharmacy claims within 6 month before season • Successfully matched to birth certificate via SSN and DoB • Cohort Set-up • Entry during any RSV season month (Oct-Mar) after 2 months in ambulatory care • Children could re-enter for a second season • Censoring at end of season, loss of eligibility, death, hospitalization for other reason • Exposure • Palivizumab use determined from pharmacy or physician charges • Current use: claim date plus 30 days according to pharmakokinetics • Former use: day 31 to 60 post claim; overridden by subsequent claim • No use: period before first dose and after former use period(s) • Outcome • First RSV-related hospitalization (ICD9-CM 480.1, 466.11, 079.6) • Analysis • Cox regression, allowing interaction between younger (2-12 months at index date) and older (13-24 months at index date) children and palivizumab use, while adjusting for other RSV risk factors (see tables). Conclusions Age appears to be a significant effect modifier of the impact of palivizumab on RSV hospitalization risk. Given the rapid decrease of RSV risk with increasing age and the effect modification, careful examination of age thresholds for immunoprophylaxis is warranted. The authors have no conflict of interest. The study was funded in part by the Florida Agency for Healthcare Administration. It was conducted in collaboration with the University of Florida Center for Medicaid and the Uninsured. The authors thank Public Health Statistics, Office of Vital Statistics, Florida Department of Health and the Texas Department of State Health Services for the provision of birth and death certificates; and the Centers for Medicare and Medicaid for provision of MAX data.