title: Prevalence of Anti-infliximab Antibodies and Their Associated Co-factors in Children with Refractory Arthritis and/or Uveitis: A Retrospective Longitudinal Cohort Study.
abstract: Infliximab (IFX) is a monoclonal tumor necrosis factor-α-inhibiting antibody used in children with refractory arthritis and uveitis. Immunogenicity is associated with a lack of clinical response and infusion reactions in adults; data on immunogenicity in children treated with IFX for rheumatic diseases are scarce. We aimed to describe the prevalence of anti-IFX antibodies and determine co-factors associated with anti-IFX antibodies in children with inflammatory rheumatic and ocular diseases.
  
  
  
  Consecutive children treated between August 2009 and August 2012 with IFX at our department were included. Blood samples were collected every 6 months before IFX infusion and tested for anti-IFX antibodies by radioimmunoassay. Patients' charts were retrospectively reviewed for clinical features and analyzed for associations with anti-IFX antibodies.
  
  
  
  Anti-IFX antibodies occurred in 14/62 children (23%) and 32/253 blood samples (12.6%) after a mean treatment time of 1084 days (range 73-3498). Infusion reactions occurred in 10/62 (16%) children during the treatment period. With continuation of IFX, anti-IFX antibodies disappeared in 7/14 children. In the bivariate analysis, the occurrence of anti-IFX antibodies was associated with younger age at IFX treatment start (mean age 7.01 vs 9.88 yrs, p = 0.003) and infusion reactions (OR 15.0), while uveitis as treatment indication was protective against development of anti-IFX antibodies (OR 0.17), likely because of higher IFX doses. In the multivariate logistic regression, all 3 covariates remained highly significant.
  
  
  
  Anti-IFX antibodies occurred commonly at any time during IFX treatment. Anti-IFX antibodies were associated with younger age at IFX start, infusion reactions, and arthritis as treatment indication.
authors.affiliation: From the Department of Rheumatology, University Children's Hospital, Zurich; RehaClinic Bad Zurzach, Bad Zurzach; Department of Pediatrics, Ostschweizer Kinderspital, St. Gallen, Switzerland; Laboratory for Biologicals, Sanquin; Department of Immunopathology, Sanquin Research; Landsteiner Academic Medical Centre, Amsterdam, the Netherlands; Department of Pediatrics, Kantonsspital Winterthur, Winterthur, Switzerland.|F.A. Aeschlimann, MD, rheumatology fellow, currently at the Division of Rheumatology, The Hospital for Sick Children, Toronto, Ontario, Canada; F. Angst, MD, MPH, RehaClinic Bad Zurzach; K.D. Hofer, medical student, Department of Rheumatology, University Children's Hospital; E. Cannizzaro Schneider, MD, staff pediatric rheumatologist, Department of Rheumatology, University Children's Hospital; S. Schroeder-Kohler, MD, staff pediatric rheumatologist, Department of Rheumatology, University Children's Hospital; R. Lauener, MD, Professor, head of pediatric department, Ostschweizer Kinderspital; D. van der Kleij, PhD, head of Laboratory for Biologicals, Sanquin; T. Rispens, PhD, Department of Immunopathology, Sanquin Research, and Landsteiner Laboratory Academic Medical Centre; R.K. Saurenmann, MD, Professor, head of pediatric department, pediatric rheumatologist, Department of Rheumatology, University Children's Hospital, and Kantonsspital Winterthur.
authors.forename: Florence A
authors.initials: FA
authors.lastname: Aeschlimann
authors.affiliation: From the Department of Rheumatology, University Children's Hospital, Zurich; RehaClinic Bad Zurzach, Bad Zurzach; Department of Pediatrics, Ostschweizer Kinderspital, St. Gallen, Switzerland; Laboratory for Biologicals, Sanquin; Department of Immunopathology, Sanquin Research; Landsteiner Academic Medical Centre, Amsterdam, the Netherlands; Department of Pediatrics, Kantonsspital Winterthur, Winterthur, Switzerland.|F.A. Aeschlimann, MD, rheumatology fellow, currently at the Division of Rheumatology, The Hospital for Sick Children, Toronto, Ontario, Canada; F. Angst, MD, MPH, RehaClinic Bad Zurzach; K.D. Hofer, medical student, Department of Rheumatology, University Children's Hospital; E. Cannizzaro Schneider, MD, staff pediatric rheumatologist, Department of Rheumatology, University Children's Hospital; S. Schroeder-Kohler, MD, staff pediatric rheumatologist, Department of Rheumatology, University Children's Hospital; R. Lauener, MD, Professor, head of pediatric department, Ostschweizer Kinderspital; D. van der Kleij, PhD, head of Laboratory for Biologicals, Sanquin; T. Rispens, PhD, Department of Immunopathology, Sanquin Research, and Landsteiner Laboratory Academic Medical Centre; R.K. Saurenmann, MD, Professor, head of pediatric department, pediatric rheumatologist, Department of Rheumatology, University Children's Hospital, and Kantonsspital Winterthur.
authors.forename: Felix
authors.initials: F
authors.lastname: Angst
authors.affiliation: From the Department of Rheumatology, University Children's Hospital, Zurich; RehaClinic Bad Zurzach, Bad Zurzach; Department of Pediatrics, Ostschweizer Kinderspital, St. Gallen, Switzerland; Laboratory for Biologicals, Sanquin; Department of Immunopathology, Sanquin Research; Landsteiner Academic Medical Centre, Amsterdam, the Netherlands; Department of Pediatrics, Kantonsspital Winterthur, Winterthur, Switzerland.|F.A. Aeschlimann, MD, rheumatology fellow, currently at the Division of Rheumatology, The Hospital for Sick Children, Toronto, Ontario, Canada; F. Angst, MD, MPH, RehaClinic Bad Zurzach; K.D. Hofer, medical student, Department of Rheumatology, University Children's Hospital; E. Cannizzaro Schneider, MD, staff pediatric rheumatologist, Department of Rheumatology, University Children's Hospital; S. Schroeder-Kohler, MD, staff pediatric rheumatologist, Department of Rheumatology, University Children's Hospital; R. Lauener, MD, Professor, head of pediatric department, Ostschweizer Kinderspital; D. van der Kleij, PhD, head of Laboratory for Biologicals, Sanquin; T. Rispens, PhD, Department of Immunopathology, Sanquin Research, and Landsteiner Laboratory Academic Medical Centre; R.K. Saurenmann, MD, Professor, head of pediatric department, pediatric rheumatologist, Department of Rheumatology, University Children's Hospital, and Kantonsspital Winterthur.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Hofer
authors.affiliation: From the Department of Rheumatology, University Children's Hospital, Zurich; RehaClinic Bad Zurzach, Bad Zurzach; Department of Pediatrics, Ostschweizer Kinderspital, St. Gallen, Switzerland; Laboratory for Biologicals, Sanquin; Department of Immunopathology, Sanquin Research; Landsteiner Academic Medical Centre, Amsterdam, the Netherlands; Department of Pediatrics, Kantonsspital Winterthur, Winterthur, Switzerland.|F.A. Aeschlimann, MD, rheumatology fellow, currently at the Division of Rheumatology, The Hospital for Sick Children, Toronto, Ontario, Canada; F. Angst, MD, MPH, RehaClinic Bad Zurzach; K.D. Hofer, medical student, Department of Rheumatology, University Children's Hospital; E. Cannizzaro Schneider, MD, staff pediatric rheumatologist, Department of Rheumatology, University Children's Hospital; S. Schroeder-Kohler, MD, staff pediatric rheumatologist, Department of Rheumatology, University Children's Hospital; R. Lauener, MD, Professor, head of pediatric department, Ostschweizer Kinderspital; D. van der Kleij, PhD, head of Laboratory for Biologicals, Sanquin; T. Rispens, PhD, Department of Immunopathology, Sanquin Research, and Landsteiner Laboratory Academic Medical Centre; R.K. Saurenmann, MD, Professor, head of pediatric department, pediatric rheumatologist, Department of Rheumatology, University Children's Hospital, and Kantonsspital Winterthur.
authors.forename: Elvira
authors.initials: E
authors.lastname: Cannizzaro Schneider
authors.affiliation: From the Department of Rheumatology, University Children's Hospital, Zurich; RehaClinic Bad Zurzach, Bad Zurzach; Department of Pediatrics, Ostschweizer Kinderspital, St. Gallen, Switzerland; Laboratory for Biologicals, Sanquin; Department of Immunopathology, Sanquin Research; Landsteiner Academic Medical Centre, Amsterdam, the Netherlands; Department of Pediatrics, Kantonsspital Winterthur, Winterthur, Switzerland.|F.A. Aeschlimann, MD, rheumatology fellow, currently at the Division of Rheumatology, The Hospital for Sick Children, Toronto, Ontario, Canada; F. Angst, MD, MPH, RehaClinic Bad Zurzach; K.D. Hofer, medical student, Department of Rheumatology, University Children's Hospital; E. Cannizzaro Schneider, MD, staff pediatric rheumatologist, Department of Rheumatology, University Children's Hospital; S. Schroeder-Kohler, MD, staff pediatric rheumatologist, Department of Rheumatology, University Children's Hospital; R. Lauener, MD, Professor, head of pediatric department, Ostschweizer Kinderspital; D. van der Kleij, PhD, head of Laboratory for Biologicals, Sanquin; T. Rispens, PhD, Department of Immunopathology, Sanquin Research, and Landsteiner Laboratory Academic Medical Centre; R.K. Saurenmann, MD, Professor, head of pediatric department, pediatric rheumatologist, Department of Rheumatology, University Children's Hospital, and Kantonsspital Winterthur.
authors.forename: Silke
authors.initials: S
authors.lastname: Schroeder-Kohler
authors.affiliation: From the Department of Rheumatology, University Children's Hospital, Zurich; RehaClinic Bad Zurzach, Bad Zurzach; Department of Pediatrics, Ostschweizer Kinderspital, St. Gallen, Switzerland; Laboratory for Biologicals, Sanquin; Department of Immunopathology, Sanquin Research; Landsteiner Academic Medical Centre, Amsterdam, the Netherlands; Department of Pediatrics, Kantonsspital Winterthur, Winterthur, Switzerland.|F.A. Aeschlimann, MD, rheumatology fellow, currently at the Division of Rheumatology, The Hospital for Sick Children, Toronto, Ontario, Canada; F. Angst, MD, MPH, RehaClinic Bad Zurzach; K.D. Hofer, medical student, Department of Rheumatology, University Children's Hospital; E. Cannizzaro Schneider, MD, staff pediatric rheumatologist, Department of Rheumatology, University Children's Hospital; S. Schroeder-Kohler, MD, staff pediatric rheumatologist, Department of Rheumatology, University Children's Hospital; R. Lauener, MD, Professor, head of pediatric department, Ostschweizer Kinderspital; D. van der Kleij, PhD, head of Laboratory for Biologicals, Sanquin; T. Rispens, PhD, Department of Immunopathology, Sanquin Research, and Landsteiner Laboratory Academic Medical Centre; R.K. Saurenmann, MD, Professor, head of pediatric department, pediatric rheumatologist, Department of Rheumatology, University Children's Hospital, and Kantonsspital Winterthur.
authors.forename: Roger
authors.initials: R
authors.lastname: Lauener
authors.affiliation: From the Department of Rheumatology, University Children's Hospital, Zurich; RehaClinic Bad Zurzach, Bad Zurzach; Department of Pediatrics, Ostschweizer Kinderspital, St. Gallen, Switzerland; Laboratory for Biologicals, Sanquin; Department of Immunopathology, Sanquin Research; Landsteiner Academic Medical Centre, Amsterdam, the Netherlands; Department of Pediatrics, Kantonsspital Winterthur, Winterthur, Switzerland.|F.A. Aeschlimann, MD, rheumatology fellow, currently at the Division of Rheumatology, The Hospital for Sick Children, Toronto, Ontario, Canada; F. Angst, MD, MPH, RehaClinic Bad Zurzach; K.D. Hofer, medical student, Department of Rheumatology, University Children's Hospital; E. Cannizzaro Schneider, MD, staff pediatric rheumatologist, Department of Rheumatology, University Children's Hospital; S. Schroeder-Kohler, MD, staff pediatric rheumatologist, Department of Rheumatology, University Children's Hospital; R. Lauener, MD, Professor, head of pediatric department, Ostschweizer Kinderspital; D. van der Kleij, PhD, head of Laboratory for Biologicals, Sanquin; T. Rispens, PhD, Department of Immunopathology, Sanquin Research, and Landsteiner Laboratory Academic Medical Centre; R.K. Saurenmann, MD, Professor, head of pediatric department, pediatric rheumatologist, Department of Rheumatology, University Children's Hospital, and Kantonsspital Winterthur.
authors.forename: Desirée
authors.initials: D
authors.lastname: van der Kleij
authors.affiliation: From the Department of Rheumatology, University Children's Hospital, Zurich; RehaClinic Bad Zurzach, Bad Zurzach; Department of Pediatrics, Ostschweizer Kinderspital, St. Gallen, Switzerland; Laboratory for Biologicals, Sanquin; Department of Immunopathology, Sanquin Research; Landsteiner Academic Medical Centre, Amsterdam, the Netherlands; Department of Pediatrics, Kantonsspital Winterthur, Winterthur, Switzerland.|F.A. Aeschlimann, MD, rheumatology fellow, currently at the Division of Rheumatology, The Hospital for Sick Children, Toronto, Ontario, Canada; F. Angst, MD, MPH, RehaClinic Bad Zurzach; K.D. Hofer, medical student, Department of Rheumatology, University Children's Hospital; E. Cannizzaro Schneider, MD, staff pediatric rheumatologist, Department of Rheumatology, University Children's Hospital; S. Schroeder-Kohler, MD, staff pediatric rheumatologist, Department of Rheumatology, University Children's Hospital; R. Lauener, MD, Professor, head of pediatric department, Ostschweizer Kinderspital; D. van der Kleij, PhD, head of Laboratory for Biologicals, Sanquin; T. Rispens, PhD, Department of Immunopathology, Sanquin Research, and Landsteiner Laboratory Academic Medical Centre; R.K. Saurenmann, MD, Professor, head of pediatric department, pediatric rheumatologist, Department of Rheumatology, University Children's Hospital, and Kantonsspital Winterthur.
authors.forename: Theo
authors.initials: T
authors.lastname: Rispens
authors.affiliation: From the Department of Rheumatology, University Children's Hospital, Zurich; RehaClinic Bad Zurzach, Bad Zurzach; Department of Pediatrics, Ostschweizer Kinderspital, St. Gallen, Switzerland; Laboratory for Biologicals, Sanquin; Department of Immunopathology, Sanquin Research; Landsteiner Academic Medical Centre, Amsterdam, the Netherlands; Department of Pediatrics, Kantonsspital Winterthur, Winterthur, Switzerland. traudel.saurenmann@kispi.uzh.ch.|F.A. Aeschlimann, MD, rheumatology fellow, currently at the Division of Rheumatology, The Hospital for Sick Children, Toronto, Ontario, Canada; F. Angst, MD, MPH, RehaClinic Bad Zurzach; K.D. Hofer, medical student, Department of Rheumatology, University Children's Hospital; E. Cannizzaro Schneider, MD, staff pediatric rheumatologist, Department of Rheumatology, University Children's Hospital; S. Schroeder-Kohler, MD, staff pediatric rheumatologist, Department of Rheumatology, University Children's Hospital; R. Lauener, MD, Professor, head of pediatric department, Ostschweizer Kinderspital; D. van der Kleij, PhD, head of Laboratory for Biologicals, Sanquin; T. Rispens, PhD, Department of Immunopathology, Sanquin Research, and Landsteiner Laboratory Academic Medical Centre; R.K. Saurenmann, MD, Professor, head of pediatric department, pediatric rheumatologist, Department of Rheumatology, University Children's Hospital, and Kantonsspital Winterthur. traudel.saurenmann@kispi.uzh.ch.
authors.forename: Rotraud K
authors.initials: RK
authors.lastname: Saurenmann
mesh_terms: D000906:Antibodies / Q000097:blood*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D000069285:Infliximab / Q000276:immunology* / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D012189:Retrospective Studies; D016036:Seroepidemiologic Studies; D014605:Uveitis / Q000097:blood / Q000188:drug therapy / Q000276:immunology*
chemical_list: D000906:Antibodies; D018501:Antirheumatic Agents; D000069285:Infliximab
keywords: ANTICHIMERIC ANTIBODIES; INFLIXIMAB; INFUSION REACTIONS; JUVENILE IDIOPATHIC ARTHRITIS; UVEITIS