Restricted Palivizumab Recommendations and the Impact on RSV Hospitalizations among Infants Born at > 29 Weeks of Gestational Age: An Italian Multicenter Study

Abstract

Objective Premature infants have the highest risk of being hospitalized with respiratory syncytial virus (RSV) infections. Palivizumab is the only licensed agent for RSVhospitalization (RSVH) prophylaxis in infants born at < 35 weeks of gestational age (wGA). In 2016, the Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) has restricted the eligibility for reimbursement to infants at high risk of RSVH, ruling out palivizumab administration for infants born at > 29 wGA. The aim of the present study was to compare the incidence of RSVH in two consecutive epidemic seasons (2015–2016 vs. 2016–2017), that is, before and after the new AIFA recommendations on palivizumab eligibility. Study Design This was a noninterventional retrospective cohort study conducted at three neonatal intensive care units (NICUs) in northern Italy. Infants born at 29 and 35 wGA between March 15, 2015 and March 14, 2017 were enrolled for this study. Electronic medical charts were reviewed and parents were interviewed by telephone. Data were collected on neonatal course during NICU stay, palivizumab administration, and hospitalizations related to respiratory infections during the 1st year of life, comparing the infants born in season 1 with season 2. Results Of 632 eligible infants, data were available for 536 (262 in season 1 and 274 in season 2). Overall, RSVH occurred 1.9 and 5.1% in infants in seasons 1 and 2, respectively (odds ratio [OR] = 2.77; 95% confidence interval [CI]: 0.98–7.8, p = 0.045). When the analysis was limited to patients not exposed to palivizumab, RSVHs were recorded for 1.8 and 5.9% infants in seasons 1 and 2, respectively (OR = 3.42; 95% CI: 0.96–12.20, p = 0.045). It is noteworthy that the incidence of hospital admissions for respiratory viruses other than RSV did not differ between the two seasons. Conclusion Restricting eligibility for palivizumab reimbursement led to a significant increase in RSVH but had no impact on hospitalizations for other respiratory viruses. Future decisions on palivizumab prescription and coverage rules should be driven by a careful assessment of the cost-benefit ratio.

Real-World Studies of Respiratory Syncytial Virus Hospitalizations among Moderate/Late Preterm Infants Exposed to Passive Immunoprophylaxis with Palivizumab

“…One of the studies that met our criteria (Priante et al) also had data that compared RSVH rates before and after the 2014 guidance update. 39 This study showed an approximate doubling of RSVH after the policy change, which was implemented in 2016 in Italy. 39 Another included study (Pedraz et al) assessed changes in RSVH in a region in Spain when palivizumab was introduced, comparing two seasons before and two seasons after its introduction and revealing a fourfold reduction in RSVH.…”

“…Two were prospective, three retrospective, and one ambispective. Three of the included studies addressed the effect of changes in policy on RSVH rates [38][39][40] : one assessed the effect of introducing palivizumab in a region in Spain, 38 and two focused on the impact of guideline changes that restricted eligibility for palivizumab in the U.S. or Italy. 39,40 Among the four studies for which it was possible to calculate RSVH rates (►Table 1), exposure to palivizumab was associated with a 1.3-to 23-fold reduction in RSVH rates (weighted mean reduction 4.0-fold).…”

“…Priante et al conducted a retrospective observational cohort study of all infants born at 29 to 35 wGA in three neonatal intensive care units in Italy to assess the impact of changes in eligibility for preterm infants on RSVH rates. 39 This population was eligible for prophylaxis up to 2016, and not eligible in 2017 because of restricted recommendations for prophylaxis that limited eligibility to preterm infants born before 29 weeks of gestation. Infants meeting these criteria and born between 2015 and 2017 were identified from birth registries and administrative records.…”

A new cost-utility analysis assessing risk factor-guided prophylaxis with palivizumab for the prevention of severe respiratory syncytial virus infection in Italian infants born at 29–35 weeks’ gestational age

“…The RSVH rate for 29–31wGA infants not receiving palivizumab was 5.88%, and was abstracted from the study by Priante et al . 2019 [ 29 ] which assessed RSVH rates in Italian infants born at 29–35wGA ( Table 1 ). For 32–35wGA infants not receiving palivizumab, data from the IRST were used, since this dataset excluded infants that received prophylaxis and provided risk-group specific RSVH rates [ 12 ].…”

Adherence to the 2014 American Academy of Pediatrics palivizumab prophylaxis recommendations

“…This concern could lead to decreased adherence to the new recommendations, resulting in more patients receiving palivizumab than currently recommended. Indeed, a study by Priante et al 15 determined that restricting palivizumab administration to children born less than 29 weeks of gestational age found an increase in hospitalizations in these children due to RSV. These and other studies with similar findings have led many authors to conclude that patients born 29 to 35 gestational weeks still benefit from palivizumab administration 16–19 …”