Respiratory Illness and Respiratory Syncytial Virus Hospitalization in the Canadian Registry of Palivizumab (CARESS; 2005–2017)

Introduction: Palivizumab safely reduces respiratory syncytial virus hospitalization (RSVH) in high-risk children. Data are necessary to identify which infants receive prophylaxis and establish RSVH incidence in specific subpopulations. The objective of this study was to determine respiratory-related illness hospitalization (RIH) and RSVH in children who received palivizumab for approved indications (prematurity less than 35 weeks gestational age, bronchopulmonary dysplasia [BPD], hemodynamically significant congenital heart disease [HSCHD]) and complex medical disorders (CMD) using a Canadian registry database (CARESS).

Materials and Methods: A prospective, observational, registry of infants who received ≥1 dose of palivizumab during the 2005 to 2017 respiratory syncytial virus (RSV) seasons in 32 sites. Neonatal and demographic data were collected at enrollment. Data on palivizumab utilization, adherence, and outcomes related to respiratory illness events were collected monthly. Data were analyzed using t-tests, chi-square tests, and Cox’s proportional hazards adjusted for potential confounders. A total of 25,003 infants aged (mean 5.7 ± 6.4 months) were enrolled.

Results: Participants were typically male (56.3%), Caucasian (68.6%), and mean gestational age of 32.6 ± 5.0 weeks. Indications for palivizumab included (n, %): prematurity (15,821; 63.3%), BPD (2,104, 8.4%), HSCHD (2,626, 10.5%), and CMD (4,452, 17.8%). Patients received an average of 4 ± 1 injections, and 109,579 doses overall. Across the 12 RSV seasons, 20,964 (83.8%) children received at least all of their expected injections, 73.9% of children received their expected injections per season, and 74.8% were adherent based on interdose intervals; 1,724 infants had 2,054 hospitalizations for respiratory-related events. Compared with preterm infants, children with HSCHD and CMD had a twofold higher RIH rate (11.5 vs. 4.3%, χ² [1] = 238.5, p < 0.0005 and 10.2 vs. 4.3%, χ² [1] = 399.0, p < 0.0005), respectively, while the BPD rate was threefold higher (13.8 vs. 4.3%, χ² [1] = 227.1, p < 0.0005). Unadjusted RSVH rates following prophylaxis were similar across groups; prematurity (1.1%), BPD (2.2%), HSCHD (1.9%), CMD (1.5%) but were significantly higher in BPD (hazard ratio [HR] = 1.8 [1.3–2.6], p = 0.001) and HSCHD (HR = 1.5 [1.1–2.2], p = 0.02) but not in CMD (HR = 1.2 [0.8–1.6], p = 0.34) compared with preterm infants. Risk factors for RSVH included: siblings (HR = 1.8, 95% confidence interval [CI]: 1.3–2.5, p = 0.001), siblings in daycare (HR = 1.5, 95% CI: 1.1–2.0, p = 0.005), a family history of atopy (HR = 1.3, 95% CI: 1.0–1.7, p = 0.022), exposure to smoking in the household (HR = 1.5, 95% CI: 1.2–2.0, p = 0.001), more than five people in the household (HR = 1.7, 95% CI: 1.3–2.2, p < 0.0005), and subject in daycare (HR = 1.7, 95% CI: 1.1–2.6, p = 0.029). Infants with five risk factors were 9.0 times (p < 0.0005) more likely to be hospitalized with RSV than infants with no risk factors. Overall RIH and RSVH rates across the 12 seasons were 6.9 and 1.6%, respectively.

Conclusion: Preterm infants had the lowest RIH and RSVH rates following prophylaxis, compared with the other subpopulations. The RSVH rate in CARESS aligns closely with reports from other international registries (range: 0.7–5.3%), and is relatively low despite the fact that the database encompasses the largest group of children who have received prophylaxis for CMDs. RSVH rates may be decreasing overall in high-risk infants due to improved adherence with prophylaxis, variability in RSV epidemiology across countries, hospital admission criteria, and preventive education.

Keywords: respiratory syncytial virus; prophylaxis; palivizumab; adherence; hospitalization rates; high-risk infants; risk factors

Conflict of Interest: B.P., I.M., and K.L. have received research funding from AbbVie Corporation and compensation as advisors or lecturers from AbbVie Corporation and MedImmune. AL. has received speaker’s fees from AbbVie, Canada. M. S. has no conflict to declare.

Funding: The Canadian RSV Evaluation Study of Palivizumab (CARESS) is funded by an investigator-initiated grant from AbbVie, Canada. However, AbbVie had no role in the study design, data collection and analysis, decision to publish, or preparation of the article.