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Nita K Patel - One of the best experts on this subject based on the ideXlab platform.

  • natural polymorphisms and resistance associated mutations in the fusion protein of respiratory syncytial virus rsv effects on rsv susceptibility to Palivizumab
    The Journal of Infectious Diseases, 2012
    Co-Authors: Qing Zhu, Nita K Patel, Wei Zhu, Leslie Wachter, Josephine M Mcauliffe, Michael P Mccarthy, Joann Suzich
    Abstract:

    Specific mutations in respiratory syncytial virus (RSV) fusion protein can cause Palivizumab resistance. We assessed the incidence of sequence polymorphisms and Palivizumab resistance in clinical RSV isolates collected from immunoprophylaxis-naive subjects. Polymorphisms were identified at low frequency, and only polymorphic mutations in antigenic site A (<1% of all polymorphisms) conferred Palivizumab resistance.

  • analysis of respiratory syncytial virus preclinical and clinical variants resistant to neutralization by monoclonal antibodies Palivizumab and or motavizumab
    The Journal of Infectious Diseases, 2011
    Co-Authors: Qing Zhu, Josie M Mcauliffe, Nita K Patel, Frances Palmerhill, Chinfen Yang, Brandon Liang, Wei Zhu, Leslie Wachter, Susan Wilson, Randall S Macgill
    Abstract:

    Respiratory syncytial virus (RSV) is a member of the Pneumovirus genus in the Paramyxoviridae family. The RSV genome consists of a negative-sense, nonsegmented, single strand of RNA encoding 10 proteins [1]. RSV is an enveloped virus, and its antigenicity is determined by 2 transmembrane glycoproteins, the attachment glycoprotein (G) and the fusion (F) protein. RSV is classified into A and B subgroups, originally based on antigenic differences in the G protein [2]. RSV is the most serious respiratory pathogen in infants and young children, causing annual epidemics of bronchiolitis and pneumonia worldwide [1, 3, 4]. Overall, RSV infection is responsible for ∼2% of the hospitalization rate among infants <1 year of age [5]. This rate increases at least 4–5-fold among children at high risk of severe RSV disease, including premature infants and those with chronic lung disease of prematurity, immunodeficiency, or complicated congenital heart disease [6–12]. RSV infection in infants and children can cause lung function deterioration that may be sustained for months after the acute illness, and in some circumstances, years of recurrent wheezing or asthma may ensue [13, 14]. To date, prevention of RSV disease has only been achieved by the passive administration of RSV-specific immunoglobulin. Prophylaxis with Palivizumab (MedImmune), a humanized monoclonal antibody (mAb) that is directed against the RSV F protein, can significantly reduce the rate of RSV-related hospitalizations in high-risk infants [15, 16]. Motavizumab (MEDI-524; MedImmune), an enhanced mAb developed by affinity maturation of Palivizumab [17–19], is in clinical development. Nonclinical studies demonstrated that motavizumab was more effective than Palivizumab at neutralizing RSV in vitro. In addition, at equivalent serum and lung levels, motavizumab was shown to be superior to Palivizumab at reducing RSV infection in both the upper and lower airways of cotton rats [18]. Motavizumab and Palivizumab bind antigenic site A, a highly conserved region on the RSV F protein between amino acids 258 and 275 [20]. Similar to other RNA viruses, replication of RSV depends on an RNA polymerase that lacks proofreading and repair capability, resulting in a relatively high mutation rate. This mutability could increase the potential for the generation of resistant mutants under selective drug pressure, such as antibody prophylaxis. In vitro development of RSV A mutants resistant to Palivizumab has been reported previously. Beeler and Coelingh [20] isolated RSV monoclonal antibody resistant mutants (MARMs) containing phenotypic amino acid variations at positions 262, 275, and 276 of the F protein with use of the murine precursor to Palivizumab, mAb1129. Sullender et al [21–23] also isolated Palivizumab MARMs containing mutations at positions 268 and 272. The potential for resistance to occur was also explored during the clinical development of Palivizumab. In a prospective study using a binding assay that was predictive of Palivizumab neutralization, the investigators showed that Palivizumab bound to all 25 RSV isolates collected from patients actively receiving Palivizumab [24]. However, the number of samples was small in this study, and the assay was suboptimal for detecting minor drug-resistant viral populations. Recently, nucleotide sequence analysis of RSV isolates collected directly from nasal wash specimens from infants who received Palivizumab and still developed acute lower tract respiratory infection revealed an F protein mutation at position 272 from lysine (K) to glutamate (E). Although the susceptibility of this variant to neutralization by Palivizumab could not be determined because it did not propagate in cell culture [25], it was suggested that this K272E variant would most likely be less susceptible to neutralization by Palivizumab, because multiple in vitro-selected Palivizumab MARMs contain mutations at this position. To date, the data available on the rate of emergence of clinical resistant variants during treatment are limited. In the present study, we describe the in vitro selection and characterization of additional Palivizumab MARMs and a novel motavizumab MARM. We also examined amino acid changes in the F protein of RSV isolates collected from RSV-breakthrough patients receiving Palivizumab or motavizumab in a large phase 3 clinical study comparing motavizumab with Palivizumab (MI-CP110: Study of MEDI-524; for the prophylaxis of RSV disease in high risk children) [26]. The sensitivity of these immunoprophylaxis breakthrough isolates to motavizumab and Palivizumab was determined using recombinant RSV (rRSV). Moreover, the effect of these neutralization-resistant mutations on in vitro fitness was assessed.

  • analysis of respiratory syncytial virus preclinical and clinical variants resistant to neutralization by monoclonal antibodies Palivizumab and or motavizumab
    The Journal of Infectious Diseases, 2011
    Co-Authors: Josie M Mcauliffe, Nita K Patel, Frances Palmerhill, Chinfen Yang, Brandon Liang, Leslie Wachter, Susan Wilson, Randall S Macgill, Lan Su, Subramaniam Krishnan
    Abstract:

    BACKGROUND: Palivizumab is a US Food and Drug Administration-approved monoclonal antibody for the prevention of respiratory syncytial virus (RSV) lower respiratory disease in high-risk infants. Motavizumab, derived from Palivizumab with enhanced antiviral activity, has recently been tested in humans. Although Palivizumab escape mutants have been generated in the laboratory, the development of resistant RSV in patients receiving Palivizumab has not been reported previously. METHODS: We generated Palivizumab and motavizumab escape mutants in vitro and examined the development of resistant mutants in RSV-breakthrough patients receiving immunoprophylaxis. The effect of these mutations on neutralization by Palivizumab and motavizumab and in vitro fitness was studied. RESULTS: Antibody-resistant RSV variants selected in vitro had mutations at position 272 of the fusion protein, from lysine to asparagine, methionine, threonine, glutamine, or glutamate. Variants containing mutations at positions 272 and 275 were detected in breakthrough patients. All these variants were resistant to Palivizumab, but only the glutamate variant at position 272 demonstrated resistance to motavizumab. Mixtures of wild-type and variant RSV soon lost the resistant phenotype in the absence of selection. CONCLUSIONS: Resistant RSV variants were detected in a small subset (∼ 5%) of RSV breakthrough cases. The fitness of these variants was impaired, compared to wild-type RSV.

  • development of motavizumab an ultra potent antibody for the prevention of respiratory syncytial virus infection in the upper and lower respiratory tract
    Journal of Molecular Biology, 2007
    Co-Authors: Herren Wu, Nita K Patel, David Pfarr, Syd Johnson, Yambasu A Brewah, Robert M Woods, Wendy I White, James F Young, Peter A Kiener
    Abstract:

    Respiratory syncytial virus (RSV) is the leading cause of viral bronchiolitis and pneumonia in infants and children. Currently, Palivizumab is the only approved monoclonal antibody (mAb) for prophylaxis of RSV. However, a small percentage of patients are not protected by Palivizumab; in addition, Palivizumab does not inhibit RSV replication effectively in the upper respiratory tract. We report here the development and characterization of motavizumab, an ultra-potent, affinity-matured, humanized mAb derived from Palivizumab. Several Palivizumab variants that enhanced the neutralization of RSV in vitro by up to 44-fold were generated; however, in vivo prophylaxis of cotton rats with these antibodies conferred only about a twofold improvement in potency over Palivizumab. This unexpected small increase of in vivo potency was caused by poor serum pharmacokinetics and lung bio-availability that resulted from unexpectedly broad tissue binding. Subsequent analyses revealed that changes at three amino acids arising from the affinity maturation markedly increased the non-specific binding to various tissues. Our results suggested that kon-driven mutations are more likely to initiate non-specific binding events than koff-driven mutations. Reversion of these three residues to the original sequences greatly diminished the tissue binding. The resulting mAb, motavizumab, binds to RSV F protein 70-fold better than Palivizumab, and exhibits about a 20-fold improvement in neutralization of RSV in vitro. In cotton rats, at equivalent concentrations, motavizumab reduced pulmonary RSV titers to up to 100-fold lower levels than did Palivizumab and, unlike Palivizumab, motavizumab very potently inhibited viral replication in the upper respiratory tract. This affinity-enhanced mAb is being investigated in pivotal clinical trials. Importantly, our engineering process offers precious insights into the improvement of other therapeutic mAbs.

Jessie R. Groothuis - One of the best experts on this subject based on the ideXlab platform.

  • Improved outcomes with home-based administration of Palivizumab: results from the 2000-2004 Palivizumab Outcomes Registry.
    The Pediatric infectious disease journal, 2008
    Co-Authors: Michael Frogel, Cliff Nerwen, Marnie L. Boron, Alan H. Cohen, Paul Vanveldhuisen, Molly Harrington, Jessie R. Groothuis
    Abstract:

    BACKGROUND Palivizumab Outcomes Registry data collected during 4 years were examined to assess compliance and respiratory syncytial virus (RSV) hospitalization rates in high-risk children receiving Palivizumab prophylaxis at home compared with an outpatient setting. METHODS Prospective observational registry enrolling high-risk infants who received > or = 1 dose of Palivizumab throughout the 2000-2001 to 2003-2004 RSV seasons at participating U.S. pediatric sites. RESULTS Registry data were analyzed for compliance and RSV hospitalization outcomes in 19,548 infants receiving doses at home versus an outpatient setting. Compliance with the injection regimen was determined by comparing the number of Palivizumab injections received versus the projected number of anticipated doses and by comparing infants receiving all injections within a 35-day interval. Compliance was significantly greater for infants who received Palivizumab at home (n = 1226) as compared with those who received Palivizumab in a clinic or office (n = 17,641), whether measured by the number of doses received (88% versus 81%, P < 0.0001) or by the timing of doses (73% versus 66%, P < 0.0001). Infants who received Palivizumab at home also had fewer RSV-associated hospitalizations compared with those who received Palivizumab in a clinic or office [0.4% (5/1226) versus 1.2% (207/17,641), P = 0.0139]. CONCLUSIONS Home administration of Palivizumab was associated with a significantly higher rate of compliance and lower hospitalization rate for RSV illness in high-risk infants.

  • Use of Palivizumab for Prevention of Hospitalization as a Result of Respiratory Syncytial Virus in Infants With Cystic Fibrosis
    The Pediatric infectious disease journal, 2008
    Co-Authors: Michael E. Speer, Marnie L. Boron, Caraciolo J. Fernandes, Jessie R. Groothuis
    Abstract:

    The Palivizumab Outcomes Registry collected data on 19,548 high-risk infants who received > or =1 dose of Palivizumab and followed prospectively from 2000 through 2004. Ninety-one children with cystic fibrosis (CF) were identified who received Palivizumab off label. None of the infants with CF who received prophylaxis was hospitalized as a result of respiratory syncytial virus lower respiratory tract infection. Evaluations of Palivizumab use in infants with CF could be warranted.

  • Palivizumab prophylaxis respiratory syncytial virus and subsequent recurrent wheezing
    The Journal of Pediatrics, 2007
    Co-Authors: Eric A. F. Simões, Xavier Carbonellestrany, Ian Mitchell, Jessie R. Groothuis, C Rieger, Linda M Fredrick, Jan L L Kimpen
    Abstract:

    Objective Children who experience respiratory syncytial virus (RSV) lower respiratory tract infections (LRTIs) early in life have high rates of subsequent recurrent wheezing. Palivizumab, an anti-RSV monoclonal antibody, has 78% to 80% efficacy in preventing RSV hospitalization in premature infants without chronic lung disease. We hypothesized that Palivizumab, by ameliorating or preventing early RSV LRTI in preterm infants, might decrease later recurrent wheezing. Study design A cohort of preterm infants who had received Palivizumab and were not hospitalized for RSV (n = 191) or who never received Palivizumab (n = 230; 76 who were hospitalized for RSV and 154 who were not), were prospectively followed for 24 months beginning at a mean age of 19 months. The subjects were assessed for recurrent wheezing by caretaker or physician report. Results The incidences of recurrent wheezing and physician-diagnosed recurrent wheezing were significantly lower in the 191 Palivizumab-treated subjects (13% and 8%, respectively) compared with all 230 untreated subjects (26%, P = .001 and 16%, P = .011, respectively) and with the 154 patients in the subgroup not hospitalized for RSV LRTI (23%, P = .022 and 16%, P = .027, respectively). The effect of Palivizumab treatment remained significant after adjustment for potential confounding variables. Conclusions Our study suggests that preventing RSV LRTI with Palivizumab may reduce subsequent recurrent wheezing in premature infants.

  • Evaluation of the Safety of Palivizumab in the Second Season of Exposure in Young Children at Risk for Severe Respiratory Syncytial Virus Infection
    Drug Safety, 2003
    Co-Authors: Thierry Lacaze-masmonteil, Ian Mitchell, Juergen Seidenberg, Veerle Cossey, Martin Cihar, Michal Csader, Rienk Baarsma, Marques Valido, Paul F. Pollack, Jessie R. Groothuis
    Abstract:

    Background : Palivizumab reduces respiratory syncytial virus (RSV) hospitalisations in high-risk infants. Those with severe bronchopulmonary dysplasia may require two seasons of prophylaxis. There is concern that this humanised antibody might cause an adverse immune response in a second season of use. Objective : To evaluate and compare the occurrence of anti-Palivizumab antibodies and clinical adverse events in subjects receiving monthly Palivizumab injections for a first and second season, and to assess frequency and severity of RSV disease in the two groups. Design and Patients : Subjects aged ≤2 years at severe risk for RSV disease were designated as first season (no previous Palivizumab exposure) or second season subjects (received Palivizumab in previous RSV season). Palivizumab injections (15 mg/kg) were administered monthly for up to 5 months. Anti-Palivizumab antibody titres and serum Palivizumab concentrations were measured; adverse events were recorded. Results : No first (n = 71) or second (n = 63) season subjects experienced a significant anti-Palivizumab antibody response (titre ≥1: 80). Serum Palivizumab concentrations were similar for the two groups. Nine (12.7%) first season and 8 (12.7%) second season subjects experienced one or more serious adverse events; most were respiratory and all were considered to be not or probably not related to Palivizumab. No deaths occurred during the study. Conclusions : Monthly Palivizumab injections were not associated with adverse immune responses or adverse events in young children receiving Palivizumab for one or two seasons. Children receiving Palivizumab for a second season did not experience more severe adverse events than those receiving it for the first time.

  • Development and use of Palivizumab (Synagis): a passive immunoprophylactic agent for RSV
    Journal of Infection and Chemotherapy, 2002
    Co-Authors: Paul Pollack, Jessie R. Groothuis, G. M. Barbarotto
    Abstract:

    Palivizumab (Synagis; Abbott Laboratories), a humanized, monoclonal antibody, prevents lower respiratory tract infection by respiratory syncytial virus (RSV). RSV causes significant morbidity and mortality in young children worldwide and is particularly severe in pre-term infants, children with cardiopulmonary disease, and the immunosuppressed population. The first such genetically engineered agent to be used effectively against a human infectious disease, Palivizumab significantly reduces the number of hospitalizations caused by RSV in high-risk infants. This article reviews the preclinical development and clinical experience of Palivizumab.

Edward M Connor - One of the best experts on this subject based on the ideXlab platform.

  • motavizumab for prophylaxis of respiratory syncytial virus in high risk children a noninferiority trial
    Pediatrics, 2010
    Co-Authors: Xavier Carbonellestrany, Brian Harris, Edward M Connor, Micki Hultquist, Eric A. F. Simões, Ron Dagan, Caroline B Hall, Genevieve Losonsky
    Abstract:

    OBJECTIVE: Palivizumab reduces respiratory syncytial virus (RSV) hospitalization in children at high risk by ∼50% compared with placebo. We compared the efficacy and safety of motavizumab, an investigational monoclonal antibody with enhanced anti-RSV activity in preclinical studies, with Palivizumab. METHODS: This randomized, double-blind, multinational, phase 3, noninferiority trial assessed safety and RSV hospitalization in 6635 preterm infants aged ≤6 months at enrollment or children aged ≤24 months with chronic lung disease of prematurity who received 15 mg/kg Palivizumab or motavizumab monthly. Secondary end points included outpatient medically attended lower respiratory tract infections (MALRIs), RSV-specific LRIs, otitis media, antibiotic use, development of antimotavizumab antibodies, and motavizumab serum concentrations. RESULTS: Motavizumab recipients had a 26% relative reduction in RSV hospitalization compared with Palivizumab recipients, achieving noninferiority. Motavizumab was superior to Palivizumab for reduction of RSV-specific outpatient MALRIs (50% relative reduction). Overall, adverse events (AEs) were not significantly different between groups. Cutaneous events were reported in 2 percentage points more motavizumab recipients (7.2% vs 5.1%); most were mild, but 0.3% resulted in dosing discontinuation. Antidrug antibodies (ADA) were detected in 1.8% of motavizumab recipients. Patients with anti-drug antibody reported 6 RSV events and 17 cutaneous events. CONCLUSIONS: Children receiving prophylaxis with motavizumab or Palivizumab had low rates of RSV hospitalization; motavizumab recipients experienced 50% fewer RSV MALRIs than Palivizumab recipients. AEs were similar in both groups, although cutaneous AEs were higher for motavizumab recipients. Motavizumab may offer an improved alternative in prophylaxis for serious RSV disease in infants and children at high risk.

  • motavizumab for prophylaxis of respiratory syncytial virus in high risk children a noninferiority trial
    Pediatrics, 2010
    Co-Authors: Xavier Carbonellestrany, Brian Harris, Edward M Connor, Micki Hultquist, Eric A. F. Simões, Ron Dagan, Caroline B Hall, Genevieve Losonsky
    Abstract:

    OBJECTIVE: Palivizumab reduces respiratory syncytial virus (RSV) hospitalization in children at high risk by ∼50% compared with placebo. We compared the efficacy and safety of motavizumab, an investigational monoclonal antibody with enhanced anti-RSV activity in preclinical studies, with Palivizumab. METHODS: This randomized, double-blind, multinational, phase 3, noninferiority trial assessed safety and RSV hospitalization in 6635 preterm infants aged ≤6 months at enrollment or children aged ≤24 months with chronic lung disease of prematurity who received 15 mg/kg Palivizumab or motavizumab monthly. Secondary end points included outpatient medically attended lower respiratory tract infections (MALRIs), RSV-specific LRIs, otitis media, antibiotic use, development of antimotavizumab antibodies, and motavizumab serum concentrations. RESULTS: Motavizumab recipients had a 26% relative reduction in RSV hospitalization compared with Palivizumab recipients, achieving noninferiority. Motavizumab was superior to Palivizumab for reduction of RSV-specific outpatient MALRIs (50% relative reduction). Overall, adverse events (AEs) were not significantly different between groups. Cutaneous events were reported in 2 percentage points more motavizumab recipients (7.2% vs 5.1%); most were mild, but 0.3% resulted in dosing discontinuation. Antidrug antibodies (ADA) were detected in 1.8% of motavizumab recipients. Patients with anti-drug antibody reported 6 RSV events and 17 cutaneous events. CONCLUSIONS: Children receiving prophylaxis with motavizumab or Palivizumab had low rates of RSV hospitalization; motavizumab recipients experienced 50% fewer RSV MALRIs than Palivizumab recipients. AEs were similar in both groups, although cutaneous AEs were higher for motavizumab recipients. Motavizumab may offer an improved alternative in prophylaxis for serious RSV disease in infants and children at high risk.

  • Motavizumab for prophylaxis of respiratory syncytial virus in high-risk children: a noninferiority trial.
    Pediatrics, 2009
    Co-Authors: Xavier Carbonell-estrany, Brian Harris, Edward M Connor, Micki Hultquist, Eric A. F. Simões, Ron Dagan, Caroline B Hall, Genevieve Losonsky
    Abstract:

    Palivizumab reduces respiratory syncytial virus (RSV) hospitalization in children at high risk by approximately 50% compared with placebo. We compared the efficacy and safety of motavizumab, an investigational monoclonal antibody with enhanced anti-RSV activity in preclinical studies, with Palivizumab. This randomized, double-blind, multinational, phase 3, noninferiority trial assessed safety and RSV hospitalization in 6635 preterm infants aged <or=6 months at enrollment or children aged <or=24 months with chronic lung disease of prematurity who received 15 mg/kg Palivizumab or motavizumab monthly. Secondary end points included outpatient medically attended lower respiratory tract infections (MALRIs), RSV-specific LRIs, otitis media, antibiotic use, development of antimotavizumab antibodies, and motavizumab serum concentrations. Motavizumab recipients had a 26% relative reduction in RSV hospitalization compared with Palivizumab recipients, achieving noninferiority. Motavizumab was superior to Palivizumab for reduction of RSV-specific outpatient MALRIs (50% relative reduction). Overall, adverse events (AEs) were not significantly different between groups. Cutaneous events were reported in 2 percentage points more motavizumab recipients (7.2% vs 5.1%); most were mild, but 0.3% resulted in dosing discontinuation. Antidrug antibodies (ADA) were detected in 1.8% of motavizumab recipients. Patients with anti-drug antibody reported 6 RSV events and 17 cutaneous events. Children receiving prophylaxis with motavizumab or Palivizumab had low rates of RSV hospitalization; motavizumab recipients experienced 50% fewer RSV MALRIs than Palivizumab recipients. AEs were similar in both groups, although cutaneous AEs were higher for motavizumab recipients. Motavizumab may offer an improved alternative in prophylaxis for serious RSV disease in infants and children at high risk.

  • Safety and immunogenicity of Palivizumab (Synagis) administered for two seasons.
    The Pediatric infectious disease journal, 2005
    Co-Authors: Donald M. Null, Pablo J. Sánchez, Bernard Pollara, Penelope H. Dennehy, Jean J. Steichen, Laurence B. Givner, David Carlin, Bernard Landry, Franklin H. Top, Edward M Connor
    Abstract:

    To evaluate the safety and immunogenicity of Palivizumab, 55 children who received Palivizumab in the IMpact-RSV trial received 5 monthly doses of 15 mg/kg Palivizumab (Synagis) during the subsequent year. The single child with an antiPalivizumab titer of >1/40 had no associated serious adverse events and had expected serum Palivizumab trough concentrations. Second year Palivizumab prophylaxis was safe and well-tolerated.

  • Palivizumab prophylaxis reduces hospitalization due to respiratory syncytial virus in young children with hemodynamically significant congenital heart disease
    The Journal of Pediatrics, 2003
    Co-Authors: Timothy F Feltes, Edward M Connor, David Carlin, Franklin H. Top, Allison K Cabalka, Cody H Meissner, Franco M Piazza, Henry M Sondheimer
    Abstract:

    Abstract Objectives To evaluate the safety, tolerance, and efficacy of Palivizumab in children with hemodynamically significant congenital heart disease (CHD). Study design A randomized, double-blind, placebo-controlled trial included 1287 children with CHD randomly assigned 1:1 to receive 5 monthly intramuscular injections of 15 mg/kg Palivizumab or placebo. Children were followed for 150 days. The primary efficacy end point was antigen-confirmed respiratory syncytial virus (RSV) hospitalization. Results Palivizumab recipients had a 45% relative reduction in RSV hospitalizations (P = .003), a 56% reduction in total days of RSV hospitalization per 100 children (P = .003), and a 73% reduction in total RSV hospital days with increased supplemental oxygen per 100 children (P = .014). Adverse events were similar in the treatment groups; no child had drug discontinued for a related adverse event. Serious adverse events occurred in 55.4% of Palivizumab recipients and 63.1% of placebo recipients (P Conclusions Monthly Palivizumab (15 mg/kg IM) was safe, well-tolerated, and effective for prophylaxis of serious RSV disease in young children with hemodynamically significant CHD.

Gretchen L. Brummel - One of the best experts on this subject based on the ideXlab platform.

  • Palivizumab in congenital heart disease: should international guidelines be revised?
    Expert opinion on biological therapy, 2007
    Co-Authors: Joseph M. Geskey, Neal J. Thomas, Gretchen L. Brummel
    Abstract:

    Palivizumab has reduced the incidence of respiratory syncytial virus hospitalization in infants and children with congenital heart disease by 45%. Although the mortality rate of children with congenital heart disease hospitalized with respiratory syncytial virus infection has declined from 37% to ∼ 3% over the past 3 decades, Palivizumab has not been shown to improve mortality. There has been considerable controversy over the cost-effectiveness of administering Palivizumab according to international guidelines, including children with congenital heart disease. In particular, the number of children that need to be treated with Palivizumab to prevent one respiratory syncytial virus hospitalization increases dramatically in children > 12 months of age. As a result, the authors recommend that countries re-examine their recommendations for providing Palivizumab up to age 24 months in children with congenital heart disease.

  • Palivizumab: a review of its use in the protection of high risk infants against respiratory syncytial virus (RSV)
    Biologics : targets & therapy, 2007
    Co-Authors: Joseph M. Geskey, Neal J. Thomas, Gretchen L. Brummel
    Abstract:

    Respiratory syncytial virus (RSV) is a leading cause of hospitalization in children less than 1 year of age and causes substantial morbidity. Although there is not currently a vaccine available to prevent RSV infection, prophylaxis with the humanized monoclonal antibody Palivizumab has been shown to reduce the rate of RSV hospitalization in premature infants and those infants with chronic lung disease or congenital heart disease. Because Palivizumab has not been shown to have a beneficial clinical effect on established RSV disease such as reducing the rate of mechanical ventilation and mortality in children afflicted with RSV, there has been considerable debate as to the cost-benefit ratio of administering Palivizumab according to international guidelines. Palivizumab has demonstrated a favorable side-effect profile in clinical trials without the development of anti-Palivizumab antibodies. Future studies are needed to determine whether Palivizumab, or other more potent monoclonal antibodies which are currently undergoing clinical trials, will reduce the long-term sequelae of RSV infection such as the development of wheezing and asthma.

Tobias Strunk - One of the best experts on this subject based on the ideXlab platform.

  • Effectiveness of Palivizumab against Respiratory Syncytial Virus: Cohort and Case Series Analysis.
    The Journal of pediatrics, 2019
    Co-Authors: Hannah C Moore, Nicholas De Klerk, Peter C Richmond, Parveen Fathima, Anthony D Keil, Thomas L Snelling, Tobias Strunk
    Abstract:

    To measure the real-world effectiveness of Palivizumab immunoprophylaxis against respiratory syncytial virus (RSV)-confirmed infection before age 2 years in a population-cohort of high-risk infants. Palivizumab is funded for high-risk infants in Western Australia. We used probabilistically linked administrative data encompassing RSV laboratory-confirmed infections, hospital admissions, and Palivizumab dispensing records for a cohort of 24 329 high-risk infants admitted to neonatal intensive care units, born 2002-2013 with follow-up to 2015. We used a traditional cohort method with Cox proportional hazards regression and a self-controlled case series analysis to assess effectiveness of Palivizumab in reducing RSV-confirmed infection by number of doses. From the cohort of 24 329 infants, 271 (1.1%) received at least 1 dose of Palivizumab and 1506 (6.2%) had at least 1 RSV-confirmed infection before age 2 years. Using the traditional cohort approach, we found no protective association of Palivizumab receipt with RSV detection (adjusted hazard ratio = 0.99 [95% CI 0.5, 1.9] for 1 dose). However, using a self-controlled case series to eliminate confounding by indication, a protective association was seen with a 74% lower RSV incidence (relative incidence = 0.26; 95% CI 0.11, 0.67) following any dose of Palivizumab compared with control (nonexposed) periods. After accounting for confounding by indication through a self-controlled analysis, Palivizumab appeared effective for reducing virologically confirmed RSV in this high-risk cohort. Copyright © 2019 Elsevier Inc. All rights reserved.

  • Effectiveness of Palivizumab against Respiratory Syncytial Virus: Cohort and Case Series Analysis.
    The Journal of Pediatrics, 2019
    Co-Authors: Hannah C Moore, Nicholas De Klerk, Parveen Fathima, Anthony D Keil, Peter Richmond, Tom Snelling, Tobias Strunk
    Abstract:

    Objective To measure the real-world effectiveness of Palivizumab immunoprophylaxis against respiratory syncytial virus (RSV)-confirmed infection before age 2 years in a population-cohort of high-risk infants. Study design Palivizumab is funded for high-risk infants in Western Australia. We used probabilistically linked administrative data encompassing RSV laboratory-confirmed infections, hospital admissions, and Palivizumab dispensing records for a cohort of 24 329 high-risk infants admitted to neonatal intensive care units, born 2002-2013 with follow-up to 2015. We used a traditional cohort method with Cox proportional hazards regression and a self-controlled case series analysis to assess effectiveness of Palivizumab in reducing RSV-confirmed infection by number of doses. Results From the cohort of 24 329 infants, 271 (1.1%) received at least 1 dose of Palivizumab and 1506 (6.2%) had at least 1 RSV-confirmed infection before age 2 years. Using the traditional cohort approach, we found no protective association of Palivizumab receipt with RSV detection (adjusted hazard ratio = 0.99 [95% CI 0.5, 1.9] for 1 dose). However, using a self-controlled case series to eliminate confounding by indication, a protective association was seen with a 74% lower RSV incidence (relative incidence = 0.26; 95% CI 0.11, 0.67) following any dose of Palivizumab compared with control (nonexposed) periods. Conclusions After accounting for confounding by indication through a self-controlled analysis, Palivizumab appeared effective for reducing virologically confirmed RSV in this high-risk cohort.