title: Compassionate use experience with high-titer respiratory syncytical virus (RSV) immunoglobulin in RSV-infected immunocompromised persons.
abstract: BACKGROUND
  Respiratory syncytial virus (RSV) may cause fatal lower respiratory tract infection (LRTI) in immunocompromised patients. Ribavirin with or without standard intravenous immunoglobulin (IVIG) is frequently given although efficacy is debated. Infusion of IVIG with high levels of neutralizing antibody against RSV may offer benefit in these patients.
  
  
  METHODS
  RI-001 contains standardized levels of high-titer anti-RSV neutralizing antibody and was provided for compassionate use to 15 patients with RSV LRTI who either failed conventional therapy or had significant risk of progression. Patients were treated on day 1 with RI-001 1500 mg/kg, followed 2 days later with 750 mg/kg. Pre- and post-infusion sera were measured for RSV neutralizing antibody. Patient data were analyzed for safety related to infusion of RI-001, and clinical outcomes.
  
  
  RESULTS
  Patients ranged in age from 2 months to 71 years and 80% had hematologic malignancy or were bone marrow or hematopoietic stem cell transplant recipients. Administration was well tolerated. Pre-infusion neutralizing titers ranged from 51 to 1765 geometric mean titer (mean 646±519) and all patients demonstrated at least a 4-fold rise (mean 6410±4470) 5-10 days post infusion. Eleven of 15 improved and were discharged from the hospital. Days from positive RSV test to RI-001 treatment was shorter in survivors compared to non-survivors (4.4±2.8 vs. 20.3±21.0 days, P=.02).
  
  
  CONCLUSIONS
  Administration of RI-001 was well tolerated and resulted in significant increases in serum neutralizing antibody titers to RSV. Our data suggest that early identification of RSV and treatment with RI-001 may offer benefit.
authors.affiliation: University of Rochester School of Medicine and Rochester General Hospital, Rochester, NY, USA.
authors.forename: Ann R
authors.initials: AR
authors.lastname: Falsey
authors.affiliation: Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Koval
authors.affiliation: Department of Pediatrics and Microbiology, Immunology and Biochemistry, University of Tennessee Center for Health Sciences, Children's Foundation Research Institute at LeBonheur Children's Hospital, Memphis, TN, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: DeVincenzo
authors.affiliation: University of Rochester School of Medicine and Rochester General Hospital, Rochester, NY, USA.
authors.forename: Edward E
authors.initials: EE
authors.lastname: Walsh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D057176:Compassionate Use Trials; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D007262:Infusions, Intravenous; D017387:Investigational New Drug Application; D008297:Male; D008875:Middle Aged; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000821:virology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000998:Antiviral Agents; D015507:Drugs, Investigational; D016756:Immunoglobulins, Intravenous
keywords: RI-001; immunoglobulin; pneumonia; respiratory syncytial virus; transplant