Florence A Aeschlimann1,2, Felix Angst1,2, Kevin D Hofer1,2, Elvira Cannizzaro Schneider1,2, Silke Schroeder-Kohler1,2, Roger Lauener1,2, Desirée van der Kleij1,2, Theo Rispens1,2, Rotraud K Saurenmann3,4. 1. 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. 2. 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. 3. 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. 4. 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.
Abstract
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVE: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. METHODS: 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. RESULTS: 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. CONCLUSION: 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: Lianna Valdes; Jacob T Cox; Janine Yang; Gayatri Susarla; Samuel Han; George N Papaliodis; Lucia Sobrin Journal: Am J Ophthalmol Case Rep Date: 2022-06-25
Authors: Virginia Miraldi Utz; Sabrina Bulas; Sarah Lopper; Matthew Fenchel; Ting Sa; Mitul Mehta; Daniel Ash; Daniel J Lovell; Adam H Kaufman Journal: Pediatr Rheumatol Online J Date: 2019-11-29 Impact factor: 3.054