Effectiveness and Safety of Palivizumab for the Prevention of Serious Lower Respiratory Tract Infection Caused by Respiratory Syncytial Virus: A Systematic Review.

OBJECTIVE: Palivizumab is a humanized monoclonal antibody approved for the prevention of serious lower respiratory tract infection (LRTI) caused by respiratory syncytial virus (RSV) in infants and young children at high risk of RSV disease. This systematic review summarized evidence on the effectiveness and safety of palivizumab when used in approved populations. STUDY DESIGN: A systematic review of Phase III trials and observational studies was conducted according to the population, intervention, comparator, outcome, timing, setting (PICOTS) approach (PROSPERO, CRD42021281380). Target populations consisted of infants with a history of premature birth (≤35-week gestational age) and children aged <2 years with bronchopulmonary dysplasia (BPD) or with hemodynamically significant congenital heart disease (hs-CHD). Outcomes of interest included RSV-related hospitalization, admission to intensive care unit (ICU), requirement for mechanical ventilation, treatment-related adverse events (AEs), and RSV-related deaths. Information sources were literature search (Ovid MEDLINE and Embase), pragmatic searches, and snowballing (covering the period up to 07 September 2021). RESULTS: A total of 60 sources were included (5 Phase III trials and 55 observational studies). RSV-related hospitalization rates following palivizumab prophylaxis in Phase III trials were 1.8% in premature infants and 7.9% in children with BPD, which were significantly lower than rates in placebo arms. In the real-world setting, similar hospitalization rates were found (0.7-4.0% in premature infants [16 studies] and 0-5.5% in patients with BPD [10 studies]) with ICU admission reported in 0 to 33.3% of patients hospitalized for RSV. In Phase III trials, RSV-related mortality rates were 0.2 and 0.3%, while AEs occurred in 11% of premature and/or BPD patients and 7.2% of hs-CHD patients, consisting mainly of injection site reaction, fever, and diarrhea. Similar results were found in observational studies. CONCLUSION: This systematic review supports the effectiveness and safety of palivizumab in the indicated populations. KEY POINTS: · Systematic review supports the positive benefit-risk profile of palivizumab in the indicated populations.. · Real-world safety and effectiveness of palivizumab are consistent with Phase III trials results.. · Palivizumab reduces RSV-related hospitalizations, ICU admissions, and need for mechanical ventilation..

Increasing Rates of RSV Hospitalization among Preterm Infants: A Decade of Data.

OBJECTIVE: In 2014, the American Academy of Pediatrics (AAP) changed its policy on the use of respiratory syncytial virus immunoprophylaxis (RSV-IP) so that RSV-IP was no longer recommended for use among infants without other medical conditions born >29 weeks of gestational age (wGA). This study examines 10-year trends in RSV-IP and RSV hospitalizations among term infants and preterm infants born at 29 to 34 wGA, including the 5 RSV seasons before and 5 RSV seasons after the AAP guidance change. STUDY DESIGN: A retrospective observational cohort study of a convenience sample of infants less than 6 months of age during RSV season (November-March) born between July 1, 2008, and June 30, 2019, who were born at 29 to 34 wGA (preterm) or >37 wGA (term) in the IBM MarketScan Commercial and Multi-State Medicaid databases. We excluded infants with medical conditions that would independently qualify them for RSV-IP. We identified RSV-IP utilization along with RSV and all-cause bronchiolitis hospitalizations during each RSV season. A difference-in-difference model was used to determine if there was a significant change in the relative rate of RSV hospitalizations following the 2014 policy change. RESULTS: There were 53,535 commercially insured and 85,099 Medicaid-insured qualifying preterm infants and 1,111,670 commercially insured and 1,492,943 Medicaid-insured qualifying term infants. Following the 2014 policy change, RSV-IP utilization decreased for all infants, while hospitalization rates tended to increase for preterm infants. Rate ratios comparing preterm to term infants also increased. The relative rate for RSV hospitalization for infants born at 29 to 34 wGA increased significantly for both commercially and Medicaid-insured infants (1.95, 95% CI: 1.67-2.27, p <0.001; 1.70, 95% CI: 1.55-1.86, p <0.001, respectively). Findings were similar for all-cause bronchiolitis hospitalizations. CONCLUSION: We found that the previously identified increase in RSV hospitalization rates among infants born at 29 to 34 wGA persisted for at least 5 years following the policy change. KEY POINTS: · Immunoprophylaxis rates decreased after the 2014 American Academy of Pediatrics guidelines update.. · Rate of RSV hospitalization increased among preterm infants after the 2014 AAP guidelines update.. · Increase in RSV hospitalization persisted for at least 5 years after AAP guidelines update..

RSV-related hospitalization and outpatient palivizumab use in very preterm (born at <29 wGA) infants: 2003-2020.

Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis and pneumonia in children under one year and a leading cause of infant hospitalization. Palivizumab was approved by the FDA in 1998 as RSV immunoprophylaxis to prevent severe RSV disease in children with specific health conditions and those born at <35 weeks gestational age (wGA). This study compared RSV-related hospitalization (RSVH) and RSVH characteristics in very preterm (<29 wGA) and term (>37 wGA) infants. Using the MarketScan Commercial and Multi-State Medicaid administrative claims databases, infants born between 7/1/2003 and 6/30/2020 were identified and classified as very preterm or term. Infants with evidence of health conditions, such as congenital heart disease and cystic fibrosis, were excluded. During 2003-2020 RSV seasons (November to March), claims incurred by infants while they were <12 months old were evaluated for outpatient administration of palivizumab and RSVH. The study included 40,123 very preterm infants and 4,421,942 term infants. Rate of RSVH in very preterm infants ranged 1.5-3.8 per 100 infant-seasons in commercially insured infants and 3.5-8.4 in Medicaid insured infants and were inversely related to wGA at birth. Relative risk of RSVH in very preterm was 3-4 times higher, and ICU admissions and mechanical ventilation were more common during RSVH in very preterm infants relative to term infants. However, these outcomes were less common or less severe in very preterm infants who received outpatient palivizumab administration, despite evidence of higher baseline risk of RSVH in these infants.

Respiratory Syncytial Virus and All-Cause Bronchiolitis Hospitalizations Among Preterm Infants Using the Pediatric Health Information System (PHIS).

BACKGROUND: In 2014, the American Academy of Pediatrics stopped recommending palivizumab to otherwise healthy 29-34 weeks' gestational age (wGA) infants aged <12 months at respiratory syncytial virus (RSV) season start. Here, we compare the burden of RSV hospitalizations (RSVH) and all-cause bronchiolitis hospitalizations (BH) before and after 2014 among otherwise healthy 29-34 wGA infants hospitalized at ≤6 months of age. METHODS: A historical, observational cohort study was conducted to evaluate RSVH and BH in 29-34 wGA infants during the 2010-2017 RSV seasons using encounter data from 51 United States children's hospitals that comprise the Pediatric Health Information System. RESULTS: The overall cohort included 67 570 RSVH out of 96 281 patients with BH. wGA was known for 22 937 RSVH and 33 289 BH. For 29-34 wGA infants, there were 8.7% and 14.2% RSVH before and after 2014, respectively (P < .0001). Intensive care unit admissions increased for RSVH (from 54.5% to 64.2%; P = .0002) and BH (from 46.7% to 54.5%; P = .0005) after controlling for sex, race, comorbidity, and cluster. The total cost of care increased for RSVH from $37 million to nearly $60 million. CONCLUSIONS: RSVH, BH, and their severity increased among 29-34 wGA infants in the 3 RSV seasons following 2014.

Healthcare resource utilization and costs in the 12 months following hospitalization for respiratory syncytial virus or unspecified bronchiolitis among infants.

Aims: To examine healthcare resource utilization (HRU) and costs within 12 months after hospitalization for respiratory syncytial virus (RSVH) or unspecified bronchiolitis (UBH) in infants.Materials and methods: Infants born July 1, 2009-June 30, 2015 were identified in the MarketScan Medicaid and Commercial databases and were assigned to one of three cohorts: RSVH (with/without UBH), UBH, or comparator (no RSVH or UBH). Each infant was identified as pre-term (5 groups) or term (2 groups) based on weeks gestational age (wGA). Index dates were the first admission dates for RSVH or UBH infants and were randomly assigned to comparator infants based on time from birth to index in the RSVH cohort. HRU, all-cause costs, and incremental cost differences between hospitalized and comparator infants were assessed over 12 months post-index with and without the index hospitalization. Results were propensity score weighted to balance pre-index characteristics across hospitalization cohorts.Results: This study identified 15,872 RSVH infants, 6,081 UBH infants, and 986,087 comparator infants in the Medicaid population and 5,755 RSVH infants, 1,888 UBH infants, and 696,302 comparator infants in the commercial population. HRU in follow-up was greater for RSVH and UBH infants relative to comparator infants in both populations, including hospitalizations (commercial: 7.4%, 11.0%, 1.7%; Medicaid: 12.3%, 15.3%, 3.2%) and emergency department visits (commercial: 33.0%, 33.3%, 17.2%; Medicaid: 65.8%, 68.5%, 51.4%). HRU was highest among RSVH and UBH infants born at <29 wGA. Hospitalized infants had numerically higher follow-up costs than comparator infants, with incremental differences reaching $19,896 among Medicaid UBH infants and $37,417 among commercial RSVH infants.Limitations: RSV/UB may be miscoded in claims data.Conclusions: Infants hospitalized for RSV or UB largely had greater subsequent HRU and costs in the first year after index hospitalization than comparator infants. Absolute and incremental follow-up costs relative to comparator infants were highest among infants <29 wGA.

Trends in Utilization of Outpatient Respiratory Syncytial Virus Prophylaxis with Palivizumab among Medicaid- and Commercially Insured Infants.

INTRODUCTION: Palivizumab is indicated for the prevention of respiratory syncytial virus (RSV) infection in high-risk children. Previous palivizumab utilization studies examined prior authorization claims but did not examine utilization within insured populations as a whole. This study describes outpatient palivizumab utilization trends and characterizes high-risk infants receiving palivizumab within Medicaid- and commercially insured populations. METHODS: Infants born July 1, 2003 through June 30, 2013 were identified in the MarketScan® Multistate Medicaid and Commercial claims databases. Infants with ≥ 18 months of continuous medical insurance enrollment with pharmacy benefits after birth and evidence of chronic lung disease of prematurity (CLDP), congenital heart disease (CHD), or preterm birth without CLDP or CHD were studied. Palivizumab use and demographic and clinical characteristics were measured in infant subgroups. Outpatient palivizumab utilization rates were calculated for each seasonal year (July-June) and for each infant subgroup. RESULTS: In total, 29,350 (2.1%) Medicaid-insured and 9589 (2.5%) commercially insured infants received palivizumab and had CLDP, CHD, or were born at < 37 weeks gestational age (wGA). Infants with CLDP (82%) and those < 29 wGA (78%) had the highest utilization. Decreases in utilization rates between the 2003-2004 and 2012-2013 seasons were seen among Medicaid-insured infants born at 29-36 wGA (all P < .0001), and commercially insured infants born at 31-32 wGA (P < .0001), 33-34 wGA (P = .055), 35-36 wGA (P < .0001), and with CHD (P = .003). Utilization by month was consistent across subgroups among Medicaid- and commercially insured infants, with most doses administered from November to March. CONCLUSION: Palivizumab use is targeted to a small percentage of infants who are at highest risk of hospitalization for RSV disease. Utilization declined in recent years in both Medicaid- and commercially insured infant groups. Most palivizumab doses were administered from November to March, with most infants receiving ≤ 5 doses. FUNDING: AstraZeneca.