Evaluation of respiratory complications in a cohort of preterm infants who did not receive palivizumab monoclonal antibodies.

OBJECTIVES: to analyze the occurrence of respiratory complications over the first year of life in preterm infants who did not receive palivizumab monoclonal antibodies. METHODS: analytical retrospective cohort study with preterm infants born between 2012 and 2016 in Uberlândia, state of Minas Gerais, Brazil. Data collection occurred from January to November 2018, by consulting hospital and primary healthcare medical records. Data were processed with the Poisson regression model, with p<0.05. RESULTS: of a total of 5,213 preterm births, 504 (9.7%) met the inclusion criteria. The preterm infants in this subset were assisted 2,899 times in primary care, which resulted in 1,098 (37.5%) medical diagnoses, of which 803 (78.5%) involved the respiratory tract. Preterm babies fed on formula milk at hospital discharge had more diagnoses of respiratory diseases. Maternal age (p=0.039), respiratory diagnosis at hospital discharge (p=0.028), and number of sporadic appointments (p<0.001) showed a significant association with bronchiolitis; number of sporadic appointments showed a significant association with occurrence of respiratory diseases; and breastfeeding had a protective effect against the development of bronchiolitis. CONCLUSIONS: preterm infants who did not receive palivizumab showed a high percentage of respiratory diseases, and breastfeeding helped protect them against bronchiolitis. It is recommended that these preterm babies be monitored in primary health care.

Descriptive analysis of adverse drug reaction reports in children and adolescents from Germany: frequently reported reactions and suspected drugs.

BACKGROUND: Adverse drug reactions (ADRs) in the pediatric population may differ in types and frequencies compared to other populations. Respective studies analyzing ADR reports referring to children have already been performed for certain countries. However, differences in drug prescriptions, among others, complicate the transferability of the results from other countries to Germany or were rarely considered. Hence, the first aim of our study was to analyze the drugs and ADRs reported most frequently in ADR reports from Germany referring to children contained in the European ADR database (EudraVigilance). The second aim was to set the number of ADR reports in relation to the number of drug prescriptions. These were provided by the Research Institute for Ambulatory Health Care in Germany. METHODS: For patients aged 0-17 years 20,854 spontaneous ADR reports were received between 01/01/2000-28/2/2019. The drugs and ADRs reported most frequently were identified. Stratified analyses with regard to age, sex and drugs used "off-label" were performed. Reporting rates (number of ADR reports/number of drug prescriptions) were calculated. RESULTS: Methylphenidate (5.5%), ibuprofen (2.3%), and palivizumab (2.0%) were most frequently reported as suspected. If related to the number of drug prescriptions, the ranking changed (palivizumab, methylphenidate, ibuprofen). Irrespective of the applied drugs, vomiting (5.4%), urticaria (4.6%) and dyspnea (4.2%) were the ADRs reported most frequently. For children aged 0-1 year, drugs for the treatment of nervous system disorders and foetal exposure during pregnancy were most commonly reported. In contrast, methylphenidate ranked first in children older than 6 years and referred 3.5 times more often to males compared to females. If age- and sex-specific exposure was considered, more ADR reports for methylphenidate referred to children 4-6 years and females 13-17 years. Drugs for the treatment of nervous system disorders ranked first among "off-label" ADR reports. CONCLUSIONS: Our analysis underlines the importance of putting the number of ADR reports of a drug in context with its prescriptions. Additionally, differences in age- and sex-stratified analysis were observed which may be associated with age- and sex-specific diseases and, thus, drug exposure. The drugs most frequently included in "off-label" ADR reports differed from those most often used according to literature.

Pharmacological management of human respiratory syncytial virus infection.

INTRODUCTION: Human respiratory syncytial virus (hRSV) is the primary viral cause of respiratory diseases, leading to bronchiolitis and pneumonia in vulnerable populations. The only current treatment against this virus is palliative, and no efficient and specific vaccine against this pathogen is available. AREAS COVERED: The authors describe the disease symptoms caused by hRSV, the economic and social impact of this infection worldwide, and how this infection can be modulated using pharmacological treatments, preventing and limiting its dissemination. The authors discuss the use of antibodies as prophylactic tools -such as palivizumab- and the use of nonspecific drugs to decrease the symptoms associated with the infection -such as bronchodilators, corticoids, and antivirals. They also discuss current vaccine candidates, new prophylactic treatments, and new antivirals options, which are currently being tested. EXPERT OPINION: Today, many researchers are focused on developing different strategies to modulate the symptoms induced by hRSV. However, to achieve this, understanding how current treatments are working and their shortcomings needs to be further elucidated.

Long term follow-up of Palivizumab administration in children born at 29-32 weeks of gestation.

BACKGROUND: Severe respiratory syncytial virus (RSV) bronchiolitis requiring hospitalization induces long term immunological and respiratory abnormalities. The long-term immunomodulation effect of Palivizumab (RSV monoclonal antibody) prophylaxis and its impact on the development of asthma remain controversial. Our aim was to evaluate airway hyper-reactivity, systemic inflammatory markers, allergic parameters and respiratory morbidity, 5-7 years following Palivizumab administration to children born at 29-32 weeks of gestation (WGA). METHODS: Children born at 29-32 WGA were evaluated at age 5-7 years. Methacholine challenge test (MCT), serum inflammatory cytokines, fractional exhaled nitric oxide (FeNO), blood tests for eosinophil count, IgE and assessment of respiratory morbidity by questionnaire were compared between those born before Palivizumab prophylaxis was extended to 29-32 WGA and those who received Palivizumab prophylaxis. RESULTS: Of 42 children recruited, 27 received Palivizumab and 15 did not. The mean gestational age and weight were lower in the Palivizumab group. Similar values of spirometry, MCT, FeNO and allergic parameters were observed in the two groups. The Palivizumab group had higher IL4, IL5 and IL13 (Th2 cytokines), IL6, IL17α, and G-CSF (Th17 activation), and lower IL12 and higher INF-γ (Th1 cytokines). CONCLUSION: Compared to children who did not receive immunoprophylaxis, among children who received Palivizumab, no beneficial effects on long-term respiratory morbidity, airway reactivity or allergic parameters were observed, and levels of Th2 and Th17 cytokines implicated in the pathogenesis of asthma were higher. These findings cast doubt on the potential long-term beneficial effect of Palivizumab on asthma inception.

Clinical characteristics and treatment outcomes among respiratory syncytial virus (RSV)-infected hematologic malignancy and hematopoietic stem cell transplant recipients receiving palivizumab.

Palivizumab has been used to treat respiratory syncytial virus (RSV)-infected hematologic malignancy patients at our institution based on limited published data. We conducted this retrospective study to evaluate clinical outcomes and mortality rates of RSV-infected hematologic malignancy patients from 2007 to 2016. A total of 67 patients (19 received palivizumab and 47 received supportive care) were identified. Palivizumab-treated patients had a significantly higher proportion of underlying ischemic heart disease, graft-versus-host-disease, hypogammaglobulinemia, and concomitant pulmonary infections. There were no significant differences in mortality rates or readmission rates between the two groups. The estimated odds ratio for death in patients receiving palivizumab after adjusting for propensity scores and covariates were 0.12 ([0.01, 1.32], p = .08) and 0.09 ([0.01, 1.03], p = .05) respectively. After adjustment for factors associated with severity of illness, there was no difference in mortality among patients treated with palivizumab.

Risk Factors and Main Indications for Palivizumab Prophylaxis in a Second Season Population: Results From the German Synagis Registry 2009-2016.

BACKGROUND: After national recommendations, palivizumab is administered in Germany to high-risk infants to prevent hospitalizations related to respiratory syncytial virus (RSV) infection. Limited data are available to characterize those children who receive palivizumab in 2 consecutive RSV seasons. METHODS: This was a comparative analysis of data from a postmarketing observational study (German SYNAGIS Registry, AbbVie Germany GmbH & Co.KG, Wiesbaden) detailing RSV-related risk factors and main indications for palivizumab in 920 children who received at ≥1 palivizumab injection in a second season between 2010 and 2016 [second season population (SSP)]. RESULTS: Median birth weight and gestational age at birth as well as the proportion of children with hemodynamically significant congenital heart disease, with any form of chronic lung disease of prematurity or with any form of neuromuscular impairment, were significantly higher in the SSP. Accordingly, hemodynamically significant congenital heart disease, chronic lung disease and other reasons (including neuromuscular impairment) and not prematurity were the main indications for palivizumab in the SSP. The RSV-related hospitalization rate confirmed by viral testing in the SSP (receiving palivizumab prophylaxis) was 0.9%. No deaths due to RSV were reported. CONCLUSIONS: Second season recipients of palivizumab differ from one season recipients of palivizumab in terms of risk factors and main indications for prophylaxis. Keeping in mind the limitations of an uncontrolled prospective observational study, these results support the effectiveness of palivizumab (concerning the RSV rehospitalization rate) and do not reveal new safety alerts in a large SSP.

Palivizumab prophylaxis for respiratory syncytial virus in infants with cystic fibrosis: is there a need?

Respiratory syncytial virus (RSV) infection in cystic fibrosis (CF) infants is associated with significant morbidities. This study's objective is to evaluate the effectiveness and adverse events related to palivizumab (PVZ) in CF infants. Data on respiratory-related illness (RIH) and RSV hospitalizations (RSVH) were collected retrospectively in CF infants aged < 2 years in Alberta, Canada, from 2000 to 2017. Logistic regression models were used to compare the odds of RSVH or RIH in PVZ infants from the Canadian registry of palivizumab (CARESS) versus untreated (UPVZ) infants from Alberta, after adjusting for potential confounders. Illness severity was compared between cohorts using χ2 and t tests. A total of 267 CF infants were included: 183 (PVZ) and 84 (UPVZ). A total of 53.3% were tested for RSV. Fifty-five infants experienced a RIH and 10 had a RSVH. The PVZ cohort experienced similar odds of RSVH but decreased odds of RIH versus UPVZ, adjusting for gestational age, birth weight, birth during RSV peak months, and presence of siblings (Exp(B) = 0.23 [0.11-0.49], p < 0.0005). In RSVH-related subjects, PVZ subjects experienced shorter length of overall stay (LOS; t = 2.39 [df = 7], p = 0.048). In those with a RIH, the PVZ group had shorter overall intensive care unit (t = 3.52 [df = 15], p = 0.003) and hospital LOS (t = 2.11 [df = 52], p = 0.04). No serious adverse events were related to PVZ. The odds of RSVH were similar between groups, but PVZ subjects had decreased odds of RIH. The low number of RSV tests performed may explain the similarity in RSVH rates. Significant differences in LOS may indicate decreased RSVH and RIH illness severity in the PVZ versus UPVZ groups.

One-year observational study of palivizumab prophylaxis on infants at risk for respiratory syncytial virus infection in Latin America / Estudo observacional de um ano da profilaxia com palivizumabe em neonatos com risco para infecção por vírus sincicial respiratório na América Latina

Abstract Objective: This study aims to describe real world palivizumab use and effectiveness in high-risk Latin American infants and young children. Method: Prospective, multicenter observational study with infants at risk for severe RSV infection who received palivizumab according to routine clinical practice. Subjects were followed for one year with monthly visits after the first dose of palivizumab. An infant was considered adherent if receiving all the expected injections or five or fewer injections within appropriate inter-dose intervals. Annual incidence rates and risk factors of lower respiratory tract infection (LRTI) hospitalization were determined through Poisson regression models (α = 0.05). Results: The study enrolled 458 children from seven countries in Latin America, from February 2011 to September 2012. The majority (98%) were born <36 weeks gestation. Overall, patients received 83.7% of their expected injections and 86.7% completed one year of follow-up. Of the 61 LRTI hospitalizations, 12 episodes were due to RSV infection. The RSV-associated hospitalization rate was 2.9 per 100 patient-years. Bronchopulmonary dysplasia was identified as an independent risk factor for LRTI hospitalization. A total of 1165 adverse events were recorded during one year of follow-up. One hundred and two patients (22.3%) had a total of 135 serious adverse events, but no events were considered to be related to palivizumab. Conclusions: The rate of RSV hospitalization in high-risk infants in Latin America was low and aligned with those observed in randomized control trials and observational studies. Palivizumab prophylaxis appeared effective and had a good safety profile in this population.

Resumo Objetivo: Descrever o uso e a eficácia do palivizumabe no mundo real em neonatos e jovens crianças de alto risco latino-americanas. Método: Estudo observacional prospectivo multicêntrico com neonatos em risco devido a infecção grave por VSR que receberam palivizumabe de acordo com a prática clínica de rotina. Os indivíduos foram acompanhados por um ano, com visitas mensais após a primeira dose de palivizumabe. Um neonato foi considerado adepto se recebeu todas as injeções esperadas ou ≤ 5 injeções nos intervalos entre doses adequados. As taxas de incidência anuais e os fatores de risco de internação por infecção do trato respiratório inferior (ITRI) foram determinados por meio dos modelos de regressão de Poisson (α = 0,05). Resultados: O estudo inscreveu 458 crianças de sete países da América Latina, de fevereiro de 2011 a setembro de 2012. A maioria (98%) nasceu com < 36 semanas. Em geral, os pacientes receberam 83,7% de suas injeções esperadas e 86,7% completaram um ano de acompanhamento. Das 61 internações por ITRI, 12 episódios foram devidos a infecção por VSR. A taxa de internação associada ao VSR foi de 2,9 em cada 100 pacientes-ano. A displasia broncopulmonar foi identificada como um fator de risco independente da internação por ITRI. Foram registrados 1.165 eventos adversos durante um ano de acompanhamento; 122 (22,3%) apresentaram 135 eventos adversos graves, porém nenhum deles foi considerado relacionado ao palivizumabe. Conclusões: A taxa de internação por VSR em neonatos de alto risco na América Latina foi baixa e em linha com as observadas em ensaios clínicos controlados randomizados e estudos observacionais. A profilaxia com palivizumabe pareceu eficaz e com bom perfil de segurança nessa população.

Product review on the monoclonal antibody palivizumab for prevention of respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) accounts for about 20% of all respiratory infections in children below the age of 5 y. It is associated with up to 63% of all acute respiratory infections and up to 81% of all viral lower respiratory tract infections causing hospitalization in infants and young children. RSV leads to seasonal epidemics between November and April in the northern hemisphere. Most severe infections (RSV accounts for 50 to 80% of all cause bronchiolitis) affect infants younger than 6 months of age and high-risk infants including those born preterm with or without bronchopulmonary dysplasia and those with hemodynamically significant congenital heart disease up to an age of 24 months. Palivizumab, a highly potent RSV-neutralizing monoclonal antibody (Mab), has been licensed in 1998 for prophylactic use to prevent RSV associated hospitalizations in high-risk infants. This Mab is given by monthly intramuscular injection at a dose of 15 mg/kg over the RSV season (up to 5 times). Palivizumab proved to be safe and well-tolerated in this population. Concerns have been raised regarding cost-effectiveness of palivizumab and thus, palivizumab prophylaxis is mainly limited to selected high-risk infants for the first RSV season. Long-lasting Mabs will be the next future approach in the prophylaxis of RSV hospitalization until a vaccine is developed.

Passive and active immunization against respiratory syncytial virus for the young and old.

INTRODUCTION: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants worldwide and also causes significant disease in the elderly. Despite 60 years of RSV research and vaccine development, there is only one approved medicine to prevent RSV infections. Palivizumab, a monoclonal antibody (mAb) against the RSV fusion (F) protein, is indicated for preterm infants and children at high-risk for RSV infections. It is an active time in RSV vaccine and mAb development with 14 vaccines and 2 mAbs currently being tested in clinical trials as of 13 February 2017. Active vaccination of women in the third trimester or passive immunization of infants with a mAb are particularly attractive approaches as the most severe disease occurs within the first 6 months of life. Areas covered: Here, we review current approaches for preventing RSV in the young and old, describe proposed clinical endpoints for studies in pediatric and adult clinical trials and highlight results from recent and ongoing clinical studies. Expert commentary: With 16 candidates in clinical development, approval of the first RSV vaccine or mAb for the prevention of RSV in all infants or the elderly is likely to occur in the next five years.

One-year observational study of palivizumab prophylaxis on infants at risk for respiratory syncytial virus infection in Latin America.

OBJECTIVE: This study aims to describe real world palivizumab use and effectiveness in high-risk Latin American infants and young children. METHOD: Prospective, multicenter observational study with infants at risk for severe RSV infection who received palivizumab according to routine clinical practice. Subjects were followed for one year with monthly visits after the first dose of palivizumab. An infant was considered adherent if receiving all the expected injections or five or fewer injections within appropriate inter-dose intervals. Annual incidence rates and risk factors of lower respiratory tract infection (LRTI) hospitalization were determined through Poisson regression models (α=0.05). RESULTS: The study enrolled 458 children from seven countries in Latin America, from February 2011 to September 2012. The majority (98%) were born <36 weeks gestation. Overall, patients received 83.7% of their expected injections and 86.7% completed one year of follow-up. Of the 61 LRTI hospitalizations, 12 episodes were due to RSV infection. The RSV-associated hospitalization rate was 2.9 per 100 patient-years. Bronchopulmonary dysplasia was identified as an independent risk factor for LRTI hospitalization. A total of 1165 adverse events were recorded during one year of follow-up. One hundred and two patients (22.3%) had a total of 135 serious adverse events, but no events were considered to be related to palivizumab. CONCLUSIONS: The rate of RSV hospitalization in high-risk infants in Latin America was low and aligned with those observed in randomized control trials and observational studies. Palivizumab prophylaxis appeared effective and had a good safety profile in this population.

Palivizumab Exposure and the Risk of Atopic Dermatitis, Asthma and Allergic Rhinoconjunctivitis: A Cross-National, Population-Based Cohort Study.

BACKGROUND: Palivizumab is a humanized monoclonal antibody designed to provide passive immunity against respiratory syncytial virus. It is prescribed to children at high risk for severe infection with respiratory syncytial virus. However, little is known about the risk of the immune-mediated diseases atopic dermatitis, asthma, and allergic rhinoconjunctivitis after palivizumab exposure. AIM: Our objective was to investigate whether exposure to palivizumab was associated with atopic dermatitis, asthma, or allergic rhinoconjunctivitis in childhood. METHODS: This was a cross-national population-based cohort study including data from 769,523 Danish children born 1 January 1999-31 December 2010 and 581,742 Swedish children born 1 July 2005-31 December 2010. Since palivizumab is only indicated for children at the highest risk, sub-cohorts of preterm children, children with bronchopulmonary dysplasia, and children with hemodynamic significant heart disease were defined. RESULTS: Of the 1,351,265 children included, 1192 (0.09%) were exposed to palivizumab. An increased risk of asthma after palivizumab exposure was observed in the total birth cohort (hazard ratio [HR] 1.49; 95% confidence interval [CI] 1.32-1.68) and in the sub-cohort of preterm children (HR 1.24; 95% CI 1.07-1.44). However, post hoc analyses using the propensity score to balance confounding factors found no increased risk of asthma in preterm children (HR 0.91; 95% CI 0.56-1.48). No increased risks of atopic dermatitis (HR 1.18; 95% CI 0.94-1.48) or allergic rhinoconjunctivitis (HR 1.14; 95% CI 0.92-1.42) were observed. CONCLUSION: Exposure to palivizumab neither increased the risk of atopic disease nor protected against asthma.

Palivizumab Exposure and the Risk of Autoimmune Disease: A Cross-National Cohort Study.

BACKGROUND: Treatment with biologic pharmaceuticals may be associated with an increased risk of immune-mediated disease. Palivizumab is a humanized monoclonal antibody designed to provide passive immunity against respiratory syncytial virus infection. Palivizumab is primarily used in preterm children known to be immunologically immature. The long-term effect of palivizumab in terms of autoimmune diseases has not yet been investigated. AIM: Our objective was to investigate whether exposure to palivizumab was associated with the development of autoimmune diseases in children. METHODS: This was a population-based cohort study including data from 769,523 Danish children born between 1 January 1999 and 31 December 2010 and data from 581,742 Swedish children born between 1 July 2005 and 31 December 2010. RESULTS: Of the 1,351,265 children included, 1192 (0.09 %) were exposed to palivizumab. Nine cases of autoimmune disease were diagnosed among palivizumab-exposed children during the period of observation. Among the children exposed to palivizumab, one child in Denmark developed inflammatory bowel disease; in Sweden, children developed juvenile arthritis (one child), diabetes mellitus (two children), celiac disease (four children), and inflammatory bowel disease (one child). The risk of autoimmune disease was not significantly increased after palivizumab exposure (hazard ratio adjusted for age and country: 1.54; 95 % confidence interval 0.80-2.95). CONCLUSION: The risk of autoimmune disease was not increased after palivizumab exposure. Given the small number of incident cases of autoimmune disease observed, this finding should be interpreted with caution.

Consensus conference on the appropriateness of palivizumab prophylaxis in respiratory syncytial virus disease.

Respiratory syncytial virus infection represents a clinical burden among young children under 24 months. Palivizumab is the only drug licensed in Italy for the prevention of serious lower respiratory tract disease requiring hospitalization caused by respiratory syncytial virus in children at high risk. However recommendations for palivizumab prophylaxis are heterogeneous. Not all the published documents agree about the clinical indications of palivizumab; this could lead to different clinical practices and concerns about the appropriateness of prophylaxis. These issues and the lack of evidence about palivizumab prophylaxis efficacy in specific medical conditions brought on the idea of a consensus conference on the current recommendations for the management and prevention of bronchiolitis, in order to share useful indications. The goal was to perform a review of the evidence regarding the efficacy and the safety of palivizumab and give recommendations in order to harmonize its use. A structured and validated method to conduct the consensus process was adopted. The consensus conference recommends palivizumab prophylaxis in infants born before 29 weeks and younger than 12 months at the start of the epidemic season. According to evidence from literature and experts' opinion, palivizumab prophylaxis is not recommended in preterm infants of gestational age ≥29 weeks, without co-morbidity (i.e., cardiac, bronchopulmonary diseases). The experts identified some clinical rare conditions for which the decision of prophylaxis should be entrusted to the specialists. The evaluation of the appropriateness of palivizumab prophylaxis in the single patient should be documented by the specialists. Pediatr Pulmonol. 2016;51:1088-1096. © 2016 Wiley Periodicals, Inc.

Palivizumab for prophylaxis against respiratory syncytial virus infection in children with cystic fibrosis.

BACKGROUND: Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis. This is an update of a previously published review. OBJECTIVES: To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 05 May 2016. SELECTION CRITERIA: Randomised and quasi-randomised studies. DATA COLLECTION AND ANALYSIS: The authors independently extracted data and assessed risk of bias. MAIN RESULTS: One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. We judged there to be a low risk of bias with respect to the concealment of the randomization schedule (although it was not clear how this was generated) and to blinding of participants and study personnel. There is also a low risk of bias with regards to incomplete outcome data. However, we judged there to be a high risk of bias from selective reporting (summary statements presented but no data) and the fact that this industry-supported study has not been published as a full report in a peer-reviewed journal.At six months follow-up, one participant in each group was hospitalised due to respiratory syncytial virus; there were no deaths in either group. In the palivizumab and placebo groups, 86 and 90 children experienced any adverse event, while five and four children had related adverse events respectively. Nineteeen children receiving palivizumab and 16 receiving placebo suffered serious adverse events; one participant receiving palivizumab discontinued due to this. At 12 months follow-up, there were no significant differences between groups in number of Pseudomonas bacterial colonisations or change in weight-to-height ratio. AUTHORS' CONCLUSIONS: We identified one randomised controlled trial comparing five monthly doses of palivizumab to placebo in infants up to two years old with cystic fibrosis. While the overall incidence of adverse events was similar in both groups, it is not possible to draw firm conclusions on the safety and tolerability of respiratory syncytial virus prophylaxis with palivizumab in infants with cystic fibrosis. Six months after treatment, the authors reported no clinically meaningful differences in outcomes. Additional randomised studies are needed to establish the safety and efficacy of palivizumab in children with cystic fibrosis.

Evaluation of recent New Vaccine Surveillance Network data regarding respiratory syncytial virus hospitalization rates in US preterm infants.

In July 2014, the Committee on Infectious Diseases (COID) updated their guidance on the use of palivizumab, recommending against use in preterm infants 29 to 35 weeks' gestational age (wGA). A primary data source cited to support this significant change was the low respiratory syncytial virus (RSV) hospitalization rate observed in the subpopulation of preterm (<37 wGA) infants evaluated from 2000 to 2005 through the New Vaccine Surveillance Network (NVSN). Here we critically appraise the preterm infant data from the NVSN in the context of data regarding the use of palivizumab in this same time period. Data from the NVSN, an analysis of Florida Medicaid data, and a national survey of US in-hospital palivizumab administration demonstrated that during 2001 to 2007, palivizumab was administered to 59% to 83% of preterm infants born at <32 wGA and 21% to 27% of all preterm infants (<37 wGA). When the NVSN data regarding incidence of RSV hospitalization in preterm infant subgroups were evaluated as a function of chronologic age, preterm infants <32 wGA showed a paradoxical increase in RSV hospitalization with older age, with the highest risk of RSV hospitalization occurring at 18 to 23 months of age. This pattern is most consistent with a reduction in RSV hospitalizations in <32 wGA infants in the first 12 to 18 months of life due to high palivizumab use at these young ages. The NVSN data were not designed to and cannot accurately describe RSV disease burden in preterm infants given the small size of the analyzed subpopulation and the high use of palivizumab during the study period.

Serious Adverse Events in the Canadian Registry of Children Receiving Palivizumab (CARESS) for Respiratory Syncytial Virus Prevention.

OBJECTIVES: To evaluate the safety and tolerability of palivizumab for RSV prophylaxis in high-risk children in everyday practice. METHODS: High-risk children prophylaxed against RSV infection were recruited into a prospective, observational, Canadian RSV Evaluation Study of Palivizumab (CARESS) registry with active, serious adverse event (SAE) monitoring from 2008 to 2013. SAE reports were systematically collected and assessed for severity and relationship to palivizumab. Data were analyzed by Chi-square or Fisher Exact Tests to examine group differences in proportions. RESULTS: 13025 infants received 57392 injections. Hospitalizations for respiratory-related illness (RIH) were reported in 915 patients, and SAEs other than RIH were reported in 52 patients. Of these, 6 (0.05%) patients had a total of 14 hypersensitivity reactions that were deemed possibly or probably related to palivizumab (incidence: 2.8 per 10,000 patient-months). The SAEs of 42 patients were assessed as not related to palivizumab. SAEs in the remaining 4 patients were not classifiable as their records were incomplete. There were no significant demographic predictors of SAE occurrence. CONCLUSIONS: Under active surveillance, a small proportion of infants in the CARESS registry experienced SAEs that had a potential relationship with palivizumab and these appeared to be unpredictable in terms of onset. Palivizumab appears to be a safe and well-tolerated antibody for RSV prophylaxis in high-risk children in routine practice.